Long-term consequences of developmental alcohol exposure on brain structure and function: Therapeutic benefits of physical activity

Brain Sciences

Volumn 3, Issue 1, 2013, Pages

  Klintsova, Anna Y ^a   Hamilton, Gillian F ^a   Boschen, Karen E ^a  

^a UNIVERSITY OF DELAWARE   (United States)

Author keywords

Adolescence; Animal model; Apoptosis; Fetal alcohol; Hippocampus; Neurotrophins; Plasticity; Prefrontal cortex

Indexed keywords

4 AMINOBUTYRIC ACID RECEPTOR STIMULATING AGENT; AMYLOID BETA PROTEIN [1-42]; BRAIN DERIVED NEUROTROPHIC FACTOR; CASPASE 3; CYTOCHROME C; DOPAMINE; ESTRADIOL; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NERVE GROWTH FACTOR; NEUROTROPHIN 3; SEROTONIN; UNCLASSIFIED DRUG; VASCULOTROPIN;

AEROBIC EXERCISE; ALCOHOL CONSUMPTION; APOPTOSIS; BEHAVIOR DISORDER; BRAIN FUNCTION; BRAIN GROWTH; COGNITIVE DEFECT; CYTOTOXICITY; DRINKING BEHAVIOR; ELECTROPHYSIOLOGY; FETAL ALCOHOL SYNDROME; HUMAN; MAJOR DEPRESSION; METHYLATION; MICROVASCULATURE; NERVE CELL PLASTICITY; NONHUMAN; OXIDATIVE STRESS; PHYSICAL ACTIVITY; PREFRONTAL CORTEX; PRENATAL EXPOSURE; PREVALENCE; REVIEW; SOCIETY;

EID: 84908053168     PISSN: None     EISSN: 20763425     Source Type: Journal    
DOI: 10.3390/brainsci3010001     Document Type: Review

References (218)

1. Cotman, C.W.; Berchtold, N.C. Exercise: A behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002, 25, 295-301.
2. Vivar, C.; Potter, M.C.; Praag, H. All about running: Synaptic plasticity, growth factors and adult hippocampal neurogenesis. Curr. Top. Behav. Neurosci. 2012, doi:10.1007/7854_2012_1220.
3. Booth, M.L.; Okely, A.D.; Chey, T.; Bauman, A.E.; Macaskill, P. Epidemiology of physical activity participation among new south wales school students. Aust. N. Z. J. Public Health 2002, 26, 371-374.
4. Hillman, C.H.; Erickson, K.I.; Kramer, A.F. Be smart, exercise your heart: Exercise effects on brain and cognition. Nat. Rev. Neurosci. 2008, 9, 58-65.
5. Hillman, C.H.; Snook, E.M.; Jerome, G.J. Acute cardiovascular exercise and executive control function. Int. J. Psychophysiol. 2003, 48, 307-314.
6. Lucas, S.J.E.; Ainslie, P.N.; Murrell, C.J.; Thomas, K.N.; Franz, E.A.; Cotter, J.D. Effect of age on exercise-induced alterations in cognitive executive function: Relationship to cerebral perfusion. Exp. Gerontol. 2012, 47, 541-551.
7. McAuley, E.; Blissmer, B.; Marquez, D.X.; Jerome, G.J.; Kramer, A.F.; Katula, J. Social relations, physical activity, and well-being in older adults. Prev. Med. 2000, 31, 608-617.
8. Powell, K.; Paffenbarger, R., Jr. Workshop on epidemiologic and public health aspects of physical activity and exercise: A summary. Public Health Rep. 1985, 100, 118-126.
9. Van Praag, H. Exercise and the brain: Something to chew on. Trends Neurosci. 2009, 32, 283-290.
10. Winter, B.; Breitenstein, C.; Mooren, F.C.; Voelker, K.; Fobker, M.; Lechtermann, A.; Krueger, K.; Fromme, A.; Korsukewitz, C.; Floel, A.; et al. High impact running improves learning. Neurobiol. Learn. Mem. 2007, 87, 597-609.
11. Angevaren, M.; Aufdemkampe, G.; Verhaar, H.; Aleman, A.; Vanhees, L. Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst. Rev. 2008, doi:10.1002/14651858.CD005381.pub2.
12. Atkinson, H.H.; Cesari, M.; Kritchevsky, S.B.; Penninx, B.W.J.H.; Fried, L.P.; Guralnik, J.M.; Williamson, J.D. Predictors of combined cognitive and physical decline. J. Am. Geriatr. Soc. 2005, 53, 1197-1202.
13. Ahlskog, J. Does vigorous exercise have a neuroprotective effect in Parkinson disease? Neurology 2011, 77, 288-294.
14. May, P.A.; Gossage, J.P.; Kalberg, W.O.; Robinson, L.K.; Buckley, D.; Manning, M.; Hoyme, H.E. Prevalence and epidemiologic characteristics of FASD from various research methods with an emphasis on recent in-school studies. Dev. Disabil. Res. Rev. 2009, 15, 176-192.
15. Amendah, D.D.; Grosse, S.D.; Bertrand, J. Medical expenditures of children in the united states with fetal alcohol syndrome. Neurotoxicol. Teratol. 2011, 33, 322-324.
16. Centers for Disease Control and Prevention. Alcohol and Public Health. Avialable online: http://www.cdc.gov/alcohol/fact-sheets/underage-drinking.htm (accessed on 6 October 2012).
17. Lupton, C.; Burd, L.; Harwood, R. Cost of fetal alcohol spectrum disorders. Am. J. Med. Genet. C Semin. Med. Genet. 2004, 127C, 42-50.
18. Mattson, S.; Schoenfeld, A.; Riley, E.P. Teratogenic effects of alcohol on brain and behavior. Alcohol Res. Health 2001, 25, 185-191.
19. Mattson, S.N.; Riley, E.P.; Sowell, E.R.; Jernigan, T.L.; Sobel, D.F.; Jones, K.L. A decrease in the size of the basal ganglia in children with fetal alcohol syndrome. Alcohol. Clin. Exp. Res. 1996, 20, 1088-1093.
20. Yang, Y.; Roussotte, F.; Kan, E.; Sulik, K.K.; Mattson, S.N.; Riley, E.P.; Jones, K.L.; Adnams, C.M.; May, P.A.; O'Connor, M.J.; et al. Abnormal cortical thickness alterations in fetal alcohol spectrum disorders and their relationships with facial dysmorphology. Cereb. Cortex 2012, 22, 1170-1179.
21. Stevens, S.; Majors, D.; Rovet, J.; Koren, G.; Fantus, E.; Nulman, I.; Desrocher, M. Social problem solving in children with fetal alcohol spectrum disorders. J. Popul. Ther. Clin. Pharmacol. 2012, 19, e99-e110.
22. Franklin, L.; Deitz, J.; Jirikowic, T.; Astley, S. Children with fetal alcohol spectrum disorders: Problem behaviors and sensory processing. Am. J. Occup. Ther. 2008, 62, 265-273.
23. Sawyer, S.M.; Afifi, R.A.; Bearinger, L.H.; Blakemore, S.-J.; Dick, B.; Ezeh, A.C.; Patton, G.C. Adolescence: A foundation for future health. Lancet 2012, 379, 1630-1640.
24. Underage drinking Costs. Available online: http://www.udetc.org/UnderageDrinkingCosts.asp (accessed on 6 October 2012).
25. United States Department of Health and Human Services; Substance Abuse and Mental Health Services Administration; Office of Applied Studies. National Survey on Drug Use and Health, 2007 (ICPSR 23782); Inter-University Consortium for Political and Social Research (ICPSR): Ann Arbor, MI, USA, 2009.
26. Lipinski, R.J.; Hammond, P.; O'Leary-Moore, S.K.; Ament, J.J.; Pecevich, S.J.; Jiang, Y.; Budin, F.; Parnell, S.E.; Suttie, M.; Godin, E.A.; et al. Ethanol-induced face-brain dysmorphology patterns are correlative and exposure-stage dependent. PLoS One 2012, 7, e43067.
27. Sulik, K.K. Genesis of alcohol-induced craniofacial dysmorphism. Exp. Biol. Med. 2005, 230, 366-375.
28. Dobbing, J.; Sands, J. Comparative aspects of the brain growth spurt. Early Hum. Dev. 1979, 3, 79-83.
29. Casey, B.; Getz, S.; Galvan, A. The adolescent brain. Dev. Rev. 2008, 28, 62-77.
30. Archibald, S.; Fennema-Notestine, C.; Gamst, A.; Riley, E.; Mattson, S.; Jernigan, T. Brain dysmorphology in individuals with severe prenatal alcohol exposure. Dev. Med. Child Neurol. 2001, 43, 148-154.
31. Sowell, E.; Jernigan, T.; Mattson, S.; Riley, E.; Sobel, D.; Jones, K. Abnormal development of the cerebellar vermis in children prenatally exposed to alcohol: Size reduction in lobules I-V. Alcohol. Clin. Exp. Res. 1996, 20, 31-34.
32. Willford, J.; Day, R.; Aizenstein, H.; Day, N. Caudate asymmetry: A neurobiological marker of moderate prenatal alcohol exposure in young adults. Neurotoxicol. Teratol. 2010, 32, 589-594.
33. Irner, T.B.; Teasdale, T.W.; Olofsson, M. Cognitive and social development in preschool children born to women using substances. J. Addict. Dis. 2011, 31, 29-44.
34. Clarren, S.; Alvord, E.J.; Sumi, S.; Streissguth, A.; Smith, D. Brain malformations related to prenatal exposure to ethanol. J. Pediatr. 1978, 92, 457-460.
35. Wisniewski, K.; Dambska, M.; Sher, J.; Qazi, Q. A clinical neuropathological study of the fetal alcohol syndrome. Neuropediatrics 1983, 14, 197-201.
36. Klintsova, A.Y.; Cowell, R.M.; Swain, R.A.; Napper, R.M.A.; Goodlett, C.R.; Greenough, W.T. Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats: I. Behavioral results. Brain Res. 1998, 800, 48-61.
37. Pierce, D.R.; Hayar, A.; Williams, D.K.; Light, K.E. Developmental alterations in olivary climbing fiber distribution following postnatal ethanol exposure in the rat. Neuroscience 2010, 169, 1438-1448.
38. Pierce, D.R.; Williams, D.K.; Light, K.E. Purkinje cell vulnerability to developmental ethanol exposure in the rat cerebellum. Alcohol. Clin. Exp. Res. 1999, 23, 1650-1659.
39. Idrus, N.M.; Napper, R.M.A. Acute and long-term purkinje cell loss following a single ethanol binge during the early third trimester equivalent in the rat. Alcohol. Clin. Exp. Res. 2012, 36, 1365-1373.
40. Christie, B.R.; Swann, S.E.; Fox, C.J.; Froc, D.; Lieblich, S.E.; Redila, V.; Webber, A. Voluntary exercise rescues deficits in spatial memory and long-term potentiation in prenatal ethanol-exposed male rats. Eur. J. Neurosci. 2005, 21, 1719-1726.
41. Thomas, J.; Sather, T.; Whinery, L. Voluntary exercise influences behavioral development in rats exposed to alcohol during the neonatal brain growth spurt. Behav. Neurosci. 2008, 122, 1264-1273.
42. Hunt, P.S.; Jacobson, S.E.; Torok, E.J. Deficits in trace fear conditioning in a rat model of fetal alcohol exposure: Dose-response and timing effects. Alcohol 2009, 43, 465-474.
43. Murawski, N.J.; Klintsova, A.Y.; Stanton, M.E. Neonatal alcohol exposure and the hippocampus in developing male rats: Effects on behaviorally induced ca1 c-fos expression, ca1 pyramidal cell number, and contextual fear conditioning. Neuroscience 2012, 206, 89-99.
44. Schreiber, W.B.; Hunt, P.S. Deficits in trace fear conditioning induced by neonatal alcohol persist into adulthood in female rats. Dev. Psychobiol. 2012, doi:10.1002/dev.21035.
45. Schreiber, W.B.; St. Cyr, S.A.; Jablonski, S.A.; Hunt, P.S.; Klintsova, A.Y.; Stanton, M.E. Effects of exercise and environmental complexity on deficits in trace and contextual fear conditioning produced by neonatal alcohol exposure in rats. Dev. Psychobiol. 2012, doi:10.1002/dev.21052.
46. Brown, K.L.; Calizo, L.H.; Stanton, M.E. Dose-dependent deficits in dual interstimulus interval classical eyeblink conditioning tasks following neonatal binge alcohol exposure in rats. Alcohol. Clin. Exp. Res. 2008, 32, 277-293.
47. Jacobson, S.W.; Stanton, M.E.; Dodge, N.C.; Pienaar, M.; Fuller, D.S.; Molteno, C.D.; Meintjes, E.M.; Hoyme, H.E.; Robinson, L.K.; Khaole, N.; et al. Impaired delay and trace eyeblink conditioning in school-age children with fetal alcohol syndrome. Alcohol. Clin. Exp. Res. 2011, 35, 250-264.
48. Jacobson, S.W.; Stanton, M.E.; Molteno, C.D.; Burden, M.J.; Fuller, D.S.; Hoyme, H.E.; Robinson, L.K.; Khaole, N.; Jacobson, J.L. Impaired eyeblink conditioning in children with fetal alcohol syndrome. Alcohol. Clin. Exp. Res. 2008, 32, 365-372.
49. Thomas, J.D.; Tran, T.D. Choline supplementation mitigates trace, but not delay, eyeblink conditioning deficits in rats exposed to alcohol during development. Hippocampus 2012, 22, 619-630.
50. Puglia, M.P.; Valenzuela, C.F. Repeated third trimester-equivalent ethanol exposure inhibits long-term potentiation in the hippocampal CA1 region of neonatal rats. Alcohol 2010, 44, 283-290.
51. Titterness, A.K.; Christie, B.R. Prenatal ethanol exposure enhances NMDAR-dependent long-term potentiation in the adolescent female dentate gyrus. Hippocampus 2012, 22, 69-81.
52. Boehme, F.; Gil-Mohapel, J.; Cox, A.; Patten, A.; Giles, E.; Brocardo, P.S.; Christie, B.R. Voluntary exercise induces adult hippocampal neurogenesis and BDNF expression in a rodent model of fetal alcohol spectrum disorders. Eur. J. Neurosci. 2011, 33, 1799-1811.
53. Gil-Mohapel, J.; Boehme, F.; Patten, A.; Cox, A.; Kainer, L.; Giles, E.; Brocardo, P.S.; Christie, B.R. Altered adult hippocampal neuronal maturation in a rat model of fetal alcohol syndrome. Brain Res. 2011, 1384, 29-41.
54. Klintsova, A.Y.; Helfer, J.L.; Calizo, L.H.; Dong, W.K.; Goodlett, C.R.; Greenough, W.T. Persistent impairment of hippocampal neurogenesis in young adult rats following early postnatal alcohol exposure. Alcohol. Clin. Exp. Res. 2007, 31, 2073-2082.
55. Pei, J.; Job, J.; Kully-Martens, K.; Rasmussen, C. Executive function and memory in children with fetal alcohol spectrum disorder. Child Neuropsychol. 2011, 17, 290-309.
56. Rasmussen, C.; Soleimani, M.; Pei, J. Executive functioning and working memory deficits on the cantab among children with prenatal alcohol exposure. J. Popul. Ther. Clin. Pharmacol. 2011, 18, e44-e53.
57. Streissguth, A.P.; Barr, H.M.; Kogan, J.; Bookstein, F.L. Understanding the Occurrence of Secondary Disabilities in Clients with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE); Tech. Rep. No. 96-06; University of Washington Fetal Alcohol & Drug Unit: Seattle, DC, USA, August 1996.
58. Parada, M.; Corral, M.; Mota, N.; Crego, A.; Rodríguez Holguín, S.; Cadaveira, F. Executive functioning and alcohol binge drinking in university students. Addict. Behav. 2012, 37, 167-172.
59. Alves, C.; Gualano, B.; Takao, P.; Avakian, P.; Fernandes, R.; Morine, D.; Takito, M. Effects of acute physical exercise on executive functions: A comparison between aerobic and strength exercise. J. Sport Exerc. Psychol. 2012, 34, 539-549.
60. Chang, Y.; Tsai, C.; Hung, T.; So, E.; Chen, F.; Etnier, J. Effects of acute exercise on executive function: A study with a tower of london task. J. Sport Exerc. Psychol. 2011, 33, 847-865.
61. Kluding, P.M.; Tseng, B.Y.; Billinger, S.A. Exercise and executive function in individuals with chronic stroke: A pilot study. J. Neurol. Phys. Ther. 2011, 35, 11-17.
62. Brocardo, P.S.; Boehme, F.; Patten, A.; Cox, A.; Gil-Mohapel, J.; Christie, B.R. Anxiety-and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: Protective effects of voluntary physical exercise. Neuropharmacology 2012, 62, 1607-1618.
63. Rodríguez-Arias, M.; Maldonado, C.; Vidal-Infer, A.; Guerri, C.; Aguilar, M.; Miñarro, J. Intermittent ethanol exposure increases long-lasting behavioral and neurochemical effects of mdma in adolescent mice. Psychopharmacology 2011, 218, 429-442.
64. Sircar, R.; Sircar, D. Repeated ethanol treatment in adolescent rats alters cortical NMDA receptor. Alcohol 2006, 39, 51-58.
65. Sircar, R.; Basak, A.K.; Sircar, D. Repeated ethanol exposure affects the acquisition of spatial memory in adolescent female rats. Behav. Brain Res. 2009, 202, 225-231.
66. Caldwell, K.K.; Sheema, S.; Paz, R.D.; Samudio-Ruiz, S.L.; Laughlin, M.H.; Spence, N.E.; Roehlk, M.J.; Alcon, S.N.; Allan, A.M. Fetal alcohol spectrum disorder-associated depression: Evidence for reductions in the levels of brain-derived neurotrophic factor in a mouse model. Pharmacol. Biochem. Behav. 2008, 90, 614-624.
67. Maldonado-Devincci, A.M.; Badanich, K.A.; Kirstein, C.L. Alcohol during adolescence selectively alters immediate and long-term behavior and neurochemistry. Alcohol 2010, 44, 57-66.
68. Pascual, M.; Do Couto, B.R.; Alfonso-Loeches, S.; Aguilar, M.A.; Rodriguez-Arias, M.; Guerri, C. Changes in histone acetylation in the prefrontal cortex of ethanol-exposed adolescent rats are associated with ethanol-induced place conditioning. Neuropharmacology 2012, 62, 2309-2319.
69. Klintsova, A.; Matthews, J.; Goodlett, C.; Napper, R.; Greenough, W. Therapeutic motor training increases parallel fiber synapse number per purkinje neuron in cerebellar cortex of rats given postnatal binge alcohol exposure: Preliminary report. Alcohol. Clin. Exp. Res.1997, 21, 1257-1263.
70. Klintsova, A.Y.; Scamra, C.; Hoffman, M.; Napper, R.M.A.; Goodlett, C.R.; Greenough, W.T. Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats: II. A quantitative stereological study of synaptic plasticity in female rat cerebellum. Brain Res. 2002, 937, 83-93.
71. Ilg, W.; Synofzik, M.; Brötz, D.; Burkard, S.; Giese, M.; Schöls, L. Intensive coordinative training improves motor performance in degenerative cerebellar disease. Neurology 2009, 73, 1823-1830.
72. Ridgel, A.L.; Vitek, J.L.; Alberts, J.L. Forced, not voluntary, exercise improves motor function in Parkinson's disease patients. Neurorehabil. Neural Repair 2009, 23, 600-608.
73. Chin, V.S.; van Skike, C.E.; Berry, R.B.; Kirk, R.E.; Diaz-Granados, J.; Matthews, D.B. Effect of acute ethanol and acute allopregnanolone on spatial memory in adolescent and adult rats. Alcohol 2011, 45, 473-483.
74. Van Skike, C.E.; Novier, A.; Diaz-Granados, J.L.; Matthews, D.B. The effect of chronic intermittent ethanol exposure on spatial memory in adolescent rats: The dissociation of metabolic and cognitive tolerances. Brain Res. 2012, 1453, 34-39.
75. Griffin, É.W.; Mullally, S.; Foley, C.; Warmington, S.A.; O'Mara, S.M.; Kelly, Á.M. Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males. Physiol. Behav. 2011, 104, 934-941.
76. Herting, M.M.; Nagel, B.J. Aerobic fitness relates to learning on a virtual morris water task and hippocampal volume in adolescents. Behav. Brain Res. 2012, 233, 517-525.
77. Marlatt, M.W.; Potter, M.C.; Lucassen, P.J.; van Praag, H. Running throughout middle-age improves memory function, hippocampal neurogenesis, and BDNF levels in female C57BL/6J mice. Dev. Neurobiol. 2012, 72, 943-952.
78. Rhyu, I.J.; Bytheway, J.A.; Kohler, S.J.; Lange, H.; Lee, K.J.; Boklewski, J.; McCormick, K.; Williams, N.I.; Stanton, G.B.; Greenough, W.T.; et al. Effects of aerobic exercise training on cognitive function and cortical vascularity in monkeys. Neuroscience 2010, 167, 1239-1248.
79. Vaynman, S.; Ying, Z.; Gomez-Pinilla, F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur. J. Neurosci. 2004, 20, 2580-2590.
80. Kohman, R.A.; Clark, P.J.; DeYoung, E.K.; Bhattacharya, T.K.; Venghaus, C.E.; Rhodes, J.S. Voluntary wheel running enhances contextual but not trace fear conditioning. Behav. Brain Res. 2012, 226, 1-7.
81. Green, J.T.; Chess, A.C.; Burns, M.; Schachinger, K.M.; Thanellou, A. The effects of two forms of physical activity on eyeblink classical conditioning. Behav. Brain Res. 2011, 219, 165-174.
82. Schiffino, F.L.; Jablonski, S.A.; Hamilton, G.F.; St. Cyr, S.A.; Finamore, J.M.; Greenough, W.T.; Stanton, M.E.; Klintsova, A.Y. Voluntary Exercise Followed by Environmental Complexity Reverses Deficits in Trace Eyeblink Conditioning and Adult Hippocampal Neurogenesis in a Rat Model of Fetal Alcohol Spectrum Disorder. Presented at the Pavlovian Society Meeting, Baltimore, MD, USA, 14-17 October 2010.
83. Varlinskaya, E.I.; Spear, L.P. Chronic tolerance to the social consequences of ethanol in adolescent and adult sprague-dawley rats. Neurotoxicol. Teratol. 2007, 29, 23-30.
84. Van Skike, C.E.; Botta, P.; Chin, V.S.; Tokunaga, S.; McDaniel, J.M.; Venard, J.; Diaz-Granados, J.L.; Valenzuela, C.F.; Matthews, D.B. Behavioral effects of ethanol in cerebellum are age dependent: Potential system and molecular mechanisms. Alcohol. Clin. Exp. Res. 2010, 34, 2070-2080.
85. Titterness, A.K.; Wiebe, E.; Kwasnica, A.; Keyes, G.; Christie, B.R. Voluntary exercise does not enhance long-term potentiation in the adolescent female dentate gyrus. Neuroscience 2011, 183, 25-31.
86. Ceccanti, M.; Mancinelli, R.; Tirassa, P.; Laviola, G.; Rossi, S.; Romeo, M.; Fiore, M. Early exposure to ethanol or red wine and long-lasting effects in aged mice. A study on nerve growth factor, brain-derived neurotrophic factor, hepatocyte growth factor, and vascular endothelial growth factor. Neurobiol. Aging 2012, 33, 359-367.
87. Fattori, V.; Abe, S.-I.; Kobayashi, K.; Costa, L.G.; Tsuji, R. Effects of postnatal ethanol exposure on neurotrophic factors and signal transduction pathways in rat brain. J. Appl. Toxicol. 2008, 28, 370-376.
88. Heaton, M.B.; Mitchell, J.J.; Paiva, M.; Walker, D.W. Ethanol-induced alterations in the expression of neurotrophic factors in the developing rat central nervous system. Dev. Brain Res. 2000, 121, 97-107.
89. Heaton, M.B.; Moore, D.B.; Paiva, M.; Madorsky, I.; Mayer, J.; Shaw, G. The role of neurotrophic factors, apoptosis-related proteins, and endogenous antioxidants in the differential temporal vulnerability of neonatal cerebellum to ethanol. Alcohol. Clin. Exp. Res. 2003, 27, 657-669.
90. Kulkarny, V.V.; Wiest, N.E.; Marquez, C.P.; Nixon, S.C.; Valenzuela, C.F.; Perrone-Bizzozero, N.I. Opposite effects of acute ethanol exposure on gap-43 and BDNF expression in the hippocampus versus the cerebellum of juvenile rats. Alcohol 2011, 45, 461-471.
91. Light, K.E.; Ge, Y.; Belcher, S.M. Early postnatal ethanol exposure selectively decreases BDNF and truncated TrkB-T2 receptor mRNA expression in the rat cerebellum. Brain Res. Mol. Brain Res. 2001, 93, 46-55.
92. Miki, T.; Kuma, H.; Yokoyama, T.; Sumitani, K.; Matsumoto, Y.; Kusaka, T.; Warita, K.; Wang, Z.; Hosomi, N.; Magawa, T.; et al. Early postnatal ethanol exposure induces fluctuation in the expression of BDNF mRNA in the developing rat hippocampus. Acta Neurobiol. Exp. (Wars) 2008, 68, 484-493.
93. Ding, Q.; Ying, Z.; Gómez-Pinilla, F. Exercise influences hippocampal plasticity by modulating brain-derived neurotrophic factor processing. Neuroscience 2011, 192, 773-780.
94. Gomes da Silva, S.; Unsain, N.; Mascó, D.H.; Toscano-Silva, M.; de Amorim, H.A.; Silva Araújo, B.H.; Simões, P.S.R.; da Graça Naffah-Mazzacoratti, M.; Mortara, R.A.; Scorza, F.A.; et al. Early exercise promotes positive hippocampal plasticity and improves spatial memory in the adult life of rats. Hippocampus 2012, 22, 347-358.
95. Rasmussen, P.; Brassard, P.; Adser, H.; Pedersen, M.V.; Leick, L.; Hart, E.; Secher, N.H.; Pedersen, B.K.; Pilegaard, H. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp. Physiol. 2009, 94, 1062-1069.
96. Schmidt-Kassow, M.; Schädle, S.; Otterbein, S.; Thiel, C.; Doehring, A.; Lötsch, J.; Kaiser, J. Kinetics of serum brain-derived neurotrophic factor following low-intensity versus high-intensity exercise in men and women. Neuroreport 2012, 23, 889-893.
97. Um, H.-S.; Kang, E.-B.; Koo, J.-H.; Kim, H.-T.; Jin, L.; Kim, E.-J.; Yang, C.-H.; An, G.-Y.; Cho, I.-H.; Cho, J.-Y. Treadmill exercise represses neuronal cell death in an aged transgenic mouse model of Alzheimer's disease. Neurosci. Res. 2011, 69, 161-173.
98. Kiuchi, T.; Lee, H.; Mikami, T. Regular exercise cures depression-like behavior via VEGF-Flk-1 signaling in chronically stressed mice. Neuroscience 2012, 207, 208-217.
99. Latimer, C.S.; Searcy, J.L.; Bridges, M.T.; Brewer, L.D.; Popovic, J.; Blalock, E.M.; Landfield, P.W.; Thibault, O.; Porter, N.M. Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice. PLoS One 2011, 6, e26812.
100. Petkov, V.V.; Stoianovski, D.; Petkov, V.D.; Vyglenova, I. Lipid peroxidation changes in the brain in fetal alcohol syndrome. Bull. Eksp. Biol. Med. 1992, 113, 500-502.
101. Ramachandran, V.; Watts, L.T.; Maffi, S.K.; Chen, J.; Schenker, S.; Henderson, G. Ethanol-induced oxidative stress precedes mitochondrially mediated apoptotic death of cultured fetal cortical neurons. J. Neurosci. Res. 2003, 74, 577-588.
102. Olney, J.; Wozniak, D.; Jevtovic-Todorovic, V.; Farber, N.; Bittigau, P.; Ikonomidou, C. Drug-induced apoptotic neurodegeneration in the developing brain. Brain Pathol. 2002, 12, 488-498.
103. Olney, J.W.; Tenkova, T.; Dikranian, K.; Muglia, L.J.; Jermakowicz, W.J.; D'Sa, C.; Roth, K.A. Ethanol-induced caspase-3 activation in the in vivo developing mouse brain. Neurobiol. Dis. 2002, 9, 205-219.
104. Saito, M.; Chakraborty, G.; Shah, R.; Mao, R.-F.; Kumar, A.; Yang, D.-S.; Dobrenis, K.; Saito, M. Elevation of GM2 ganglioside during ethanol-induced apoptotic neurodegeneration in the developing mouse brain. J. Neurochem. 2012, 121, 649-661.
105. Tiwari, V.; Chopra, K. Attenuation of oxidative stress, neuroinflammation, and apoptosis by curcumin prevents cognitive deficits in rats postnatally exposed to ethanol. Psychopharmacology 2012, 224, 519-535.
106. Ullah, N.; Naseer, M.I.; Ullah, I.; Lee, H.Y.; Koh, P.O.; Kim, M.O. Protective effect of pyruvate against ethanol-induced apoptotic neurodegeneration in the developing rat brain. Neuropharmacology 2011, 61, 1248-1255.
107. Otero, N.K.H.; Thomas, J.D.; Saski, C.A.; Xia, X.; Kelly, S.J. Choline supplementation and DNA methylation in the hippocampus and prefrontal cortex of rats exposed to alcohol during development. Alcohol. Clin. Exp. Res. 2012, 36, 1701-1709.
108. Gomez-Pinilla, F.; Zhuang, Y.; Feng, J.; Ying, Z.; Fan, G. Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. Eur. J. Neurosci. 2011, 33, 383-390.
109. Chaddock, L.; Erickson, K.; Prakash, R.; VanPatter, M.; Voss, M.; Pontifex, M.; Raine, L.; Hillman, C.; Kramer, A. Basal ganglia volume is associated with aerobic fitness in preadolescent children. Dev. Neurosci. 2010, 32, 249-256.
110. Gomes da Silva, S.; Doná, F.; da Silva Fernandes, M.J.; Scorza, F.A.; Cavalheiro, E.A.; Arida, R.M. Physical exercise during the adolescent period of life increases hippocampal parvalbumin expression. Brain Dev. 2010, 32, 137-142.
111. Hamilton, G.F.; Whitcher, L.T.; Klintsova, A.Y. Postnatal binge-like alcohol exposure decreases dendritic complexity while increasing the density of mature spines in mpfc layer II/III pyramidal neurons. Synapse 2010, 64, 127-135.
112. Lawrence, R.C.; Otero, N.K.H.; Kelly, S.J. Selective effects of perinatal ethanol exposure in medial prefrontal cortex and nucleus accumbens. Neurotoxicol. Teratol. 2012, 34, 128-135.
113. Eadie, B.D.; Redila, V.A.; Christie, B.R. Voluntary exercise alters the cytoarchitecture of the adult dentate gyrus by increasing cellular proliferation, dendritic complexity, and spine density. J. Comp. Neurol. 2005, 486, 39-47.
114. Redila, V.A.; Christie, B.R. Exercise-induced changes in dendritic structure and complexity in the adult hippocampal dentate gyrus. Neuroscience 2006, 137, 1299-1307.
115. Whitcher, L.T.; Klintsova, A.Y. Postnatal binge-like alcohol exposure reduces spine density without affecting dendritic morphology in rat MPFC. Synapse 2008, 62, 566-573.
116. Hamilton, G.F.; Murawski, N.J.; St. Cyr, S.A.; Jablonski, S.A.; Schiffino, F.L.; Stanton, M.E.; Klintsova, A.Y. Neonatal alcohol exposure disrupts hippocampal neurogenesis and contextual fear conditioning in adult rats. Brain Res. 2011, 1412, 88-101.
117. Helfer, J.L.; Goodlett, C.R.; Greenough, W.T.; Klintsova, A.Y. The effects of exercise on adolescent hippocampal neurogenesis in a rat model of binge alcohol exposure during the brain growth spurt. Brain Res. 2009, 1294, 1-11.
118. McClain, J.A.; Hayes, D.M.; Morris, S.A.; Nixon, K. Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: Effects on cell cycle kinetics. J. Comp. Neurol. 2011, 519, 2697-2710.
119. Hamilton, G.F.; Boschen, K.E.; Goodlett, C.R.; Greenough, W.T.; Klintsova, A.Y. Housing in environmental complexity following wheel running augments survival of newly generated hippocampal neurons in a rat model of binge alcohol exposure during the third trimester equivalent. Alcohol. Clin. Exp. Res. 2012, 36, 1196-1204.
120. Bake, S.; Tingling, J.D.; Miranda, R.C. Ethanol exposure during pregnancy persistently attenuates cranially directed blood flow in the developing fetus: Evidence from ultrasound imaging in a murine second trimester equivalent model. Alcohol. Clin. Exp. Res. 2012, 36, 748-758.
121. Bhatara, V.; Lovrein, F.; Kirkeby, J.; Swayze, V., II; Unruh, E.; Johnson, V. Brain function in fetal alcohol syndrome assessed by single photon emission computed tomography. S. D. J. Med. 2002, 55, 59-62.
122. Jones, P.; Leichter, J.; Lee, M. Placental blood flow in rats fed alcohol before and during gestation. Life Sci. 1981, 29, 1153-1159.
123. Riikonen, R.; Salonen, I.; Partanen, K.; Verho, S. Brain perfusion spect and MRI in foetal alcohol syndrome. Dev. Med. Child Neurol. 1999, 41, 652-659.
124. Sato, K.; Ogoh, S.; Hirasawa, A.; Oue, A.; Sadamoto, T. The distribution of blood flow in the carotid and vertebral arteries during dynamic exercise in humans. J. Physiol. 2011, 589, 2847-2856.
125. Van der Borght, K.; Kóbor-Nyakas, D. É.; Klauke, K.; Eggen, B.J.L.; Nyakas, C.; van der Zee, E.A.; Meerlo, P. Physical exercise leads to rapid adaptations in hippocampal vasculature: Temporal dynamics and relationship to cell proliferation and neurogenesis. Hippocampus 2009, 19, 928-936.
126. Vogiatzis, I.; Louvaris, Z.; Habazettl, H.; Athanasopoulos, D.; Andrianopoulos, V.; Cherouveim, E.; Wagner, H.; Roussos, C.; Wagner, P.D.; Zakynthinos, S. Frontal cerebral cortex blood flow, oxygen delivery and oxygenation during normoxic and hypoxic exercise in athletes. J. Physiol. 2011, 589, 4027-4039.
127. Odgers, C.; Caspi, A.; Nagin, D.; Piquero, A.; Slutske, W.; Milne, B.; Dickson, N.; Poulton, R.; Moffitt, T. Is it important to prevent early exposure to drugs and alcohol among adolescents? Psychol. Sci. 2008, 19, 1037-1044.
128. Chin, V.S.; van Skike, C.E.; Matthews, D.B. Effects of ethanol on hippocampal function during adolescence: A look at the past and thoughts on the future. Alcohol 2010, 44, 3-14.
129. Guerri, C.; Pascual, M. Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence. Alcohol 2010, 44, 15-26.
130. Spear, L.P. The adolescent brain and age-related behavioral manifestations. Neurosci. Biobehav. Rev. 2000, 24, 417-463.
131. McClain, J.A.; Morris, S.A.; Deeny, M.A.; Marshall, S.A.; Hayes, D.M.; Kiser, Z.M.; Nixon, K. Adolescent binge alcohol exposure induces long-lasting partial activation of microglia. Brain Behav. Immun. 2011, 25 (Suppl. 1), S120-S128.
132. Koss, W.A.; Sadowski, R.N.; Sherrill, L.K.; Gulley, J.M.; Juraska, J.M. Effects of ethanol during adolescence on the number of neurons and glia in the medial prefrontal cortex and basolateral amygdala of adult male and female rats. Brain Res. 2012, 1466, 24-32.
133. Sircar, R.; Sircar, D. Adolescent rats exposed to repeated ethanol treatment show lingering behavioral impairments. Alcohol. Clin. Exp. Res. 2005, 29, 1402-1410.
134. Bergstrom, H.C.; McDonald, C.G.; Smith, R.F. Alcohol exposure during adolescence impairs auditory fear conditioning in adult long-evans rats. Physiol. Behav. 2006, 88, 466-472.
135. McCool, B.A. Ethanol modulation of synaptic plasticity. Neuropharmacology 2011, 61, 1097-1108.
136. Ikonomidou, C.; Bittigau, P.; Koch, C.; Genz, K.; Hoerster, F.; Felderhoff-Mueser, U.; Tenkova, T.; Dikranian, K.; Olney, J.W. Neurotransmitters and apoptosis in the developing brain. Biochem. Pharmacol. 2001, 62, 401-405.
137. Ehlers, C.L.; Criado, J.R.; Wills, D.N.; Liu, W.; Crews, F.T. Periadolescent ethanol exposure reduces adult forebrain chat+ir neurons: Correlation with behavioral pathology. Neuroscience 2011, 199, 333-345.
138. Ehrlich, D.; Pirchl, M.; Humpel, C. Effects of long-term moderate ethanol and cholesterol on cognition, cholinergic neurons, inflammation, and vascular impairment in rats. Neuroscience 2012, 205, 154-166.
139. Bales, K.R.; Tzavara, E.T.; Wu, S.; Wade, M.R.; Bymaster, F.P.; Paul, S.M.; Nomikos, G.G. Cholinergic dysfunction in a mouse model of Alzheimer disease is reversed by an anti-aß antibody. J. Clin. Invest. 2006, 116, 825-832.
140. Monk, B.R.; Leslie, F.M.; Thomas, J.D. The effects of perinatal choline supplementation on hippocampal cholinergic development in rats exposed to alcohol during the brain growth spurt. Hippocampus 2012, 22, 1750-1757.
141. Kim, E.-K.; Lee, M.-H.; Kim, H.; Sim, Y.-J.; Shin, M.-S.; Lee, S.-J.; Yang, H.-Y.; Chang, H.-K.; Lee, T.-H.; Jang, M.-H.; et al. Maternal ethanol administration inhibits 5-hydroxytryptamine synthesis and tryptophan hydroxylase expression in the dorsal raphe of rat offspring. Brain Dev. 2005, 27, 472-476.
142. Buske, C.; Gerlai, R. Early embryonic ethanol exposure impairs shoaling and the dopaminergic and serotoninergic systems in adult zebrafish. Neurotoxicol. Teratol. 2011, 33, 698-707.
143. Molet, J.; Bouaziz, E.; Hamon, M.; Lanfumey, L. Early exposure to ethanol differentially affects ethanol preference at adult age in two inbred mouse strains. Neuropharmacology 2012, 63, 338-348.
144. Dempsey, S.; Grisel, J.E.; Grisel, J.E. Locomotor sensitization to EtOH: Contribution of ß-endorphin. Front. Mol. Neurosci. 2012, 5, doi:10.3389/fnmol.2012.00087.
145. Bernier, B.E.; Whitaker, L.R.; Morikawa, H. Previous ethanol experience enhances synaptic plasticity of NMDA receptors in the ventral tegmental area. J. Neurosci. 2011, 31, 5205-5212.
146. Ramezani, A.; Goudarzi, I.; Lashkarbolouki, T.; Ghorbanian, M.T.; Elahdadi Salmani, M.; Abrari, K. Neuroprotective effects of the 17ß-estradiol against ethanol-induced neurotoxicity and oxidative stress in the developing male rat cerebellum: Biochemical, histological and behavioral changes. Pharmacol. Biochem. Behav.2011, 100, 144-151.
147. Przybycien-Szymanska, M.M.; Gillespie, R.A.; Pak, T.R. 17ß-estradiol is required for the sexually dimorphic effects of repeated binge-pattern alcohol exposure on the hpa axis during adolescence. PLoS One 2012, 7, e32263.
148. Przybycien-Szymanska, M.M.; Mott, N.N.; Paul, C.R.; Gillespie, R.A.; Pak, T.R. Binge-pattern alcohol exposure during puberty induces long-term changes in hpa axis reactivity. PLoS One 2011, 6, e18350.
149. Lan, N.; Yamashita, F.; Halpert, A.G.; Sliwowska, J.H.; Viau, V.; Weinberg, J. Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal function across the estrous cycle. Alcohol. Clin. Exp. Res. 2009, 33, 1075-1088.
150. Segal, S.; Cotman, C.; Cahill, L. Exercise-induced noradrenergic activation enhances memory consolidation in both normal aging and patients with amnestic mild cognitive impairment. J. Alzheimers Dis. 2012, 32, doi:10.3233/JAD-2012-121078.
151. Greenwood, B.N.; Foley, T.E.; Day, H.E.W.; Campisi, J.; Hammack, S.H.; Campeau, S.; Maier, S.F.; Fleshner, M. Freewheel running prevents learned helplessness/behavioral depression: Role of dorsal raphe serotonergic neurons. J. Neurosci. 2003, 23, 2889-2898.
152. Mabandla, M.; Kellaway, L.; Daniels, W.; Russell, V. Effect of exercise on dopamine neuron survival in prenatally stressed rats. Metab. Brain Dis. 2009, 24, 525-539.
153. Kim, H.; Heo, H.-I.; Kim, D.-H.; Ko, I.-G.; Lee, S.-S.; Kim, S.-E.; Kim, B.-K.; Kim, T.-W.; Ji, E.-S.; Kim, J.-D.; et al. Treadmill exercise and methylphenidate ameliorate symptoms of attention deficit/hyperactivity disorder through enhancing dopamine synthesis and brain-derived neurotrophic factor expression in spontaneous hypertensive rats. Neurosci. Lett. 2011, 504, 35-39.
154. Renoir, T.; Chevarin, C.; Lanfumey-Mongredien, L.; Hannan, A. Effect of enhanced voluntary physical exercise on brain levels of monoamines in huntington disease mice. PLoS Curr. 2011, 3, doi:10.1371/currents.RRN1281.
155. Lawlor, D.A.; Hopker, S.W. The effectiveness of exercise as an intervention in the management of depression: Systematic review and meta-regression analysis of randomised controlled trials. BMJ 2001, 322, 763.
156. Sigwalt, A.R.; Budde, H.; Helmich, I.; Glaser, V.; Ghisoni, K.; Lanza, S.; Cadore, E.L.; Lhullier, F.L.R.; de Bem, A.F.; Hohl, A.; et al. Molecular aspects involved in swimming exercise training reducing anhedonia in a rat model of depression. Neuroscience 2011, 192, 661-674.
157. Berchtold, N.C.; Kesslak, J.P.; Pike, C.J.; Adlard, P.A.; Cotman, C.W. Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus. Eur. J. Neurosci. 2001, 14, 1992-2002.
158. Erickson, K.I.; Colcombe, S.J.; Elavsky, S.; McAuley, E.; Korol, D.L.; Scalf, P.E.; Kramer, A.F. Interactive effects of fitness and hormone treatment on brain health in postmenopausal women. Neurobiol. Aging 2007, 28, 179-185.
159. Reichardt, L.F. Neurotrophin-regulated signalling pathways. Philos. Trans. R. Soc. B Biol. Sci. 2006, 361, 1545-1564.
160. Chan, J.P.; Cordeira, J.; Calderon, G.A.; Iyer, L.K.; Rios, M. Depletion of central BDNF in mice impedes terminal differentiation of new granule neurons in the adult hippocampus. Mol. Cell. Neurosci. 2008, 39, 372-383.
161. Kaufmann, W.E.; Moser, H.W. Dendritic anomalies in disorders associated with mental retardation. Cereb. Cortex 2000, 10, 981-991.
162. Kolb, J.E.; Trettel, J.; Levine, E.S. BDNF enhancement of postsynaptic NMDA receptors is blocked by ethanol. Synapse 2005, 55, 52-57.
163. Popova, N.K.; Morozova, M.V.; Naumenko, V.S. Ameliorative effect of BDNF on prenatal ethanol and stress exposure-induced behavioral disorders. Neurosci. Lett. 2011, 505, 82-86.
164. Bekinschtein, P.; Oomen, C.A.; Saksida, L.M.; Bussey, T.J. Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable? Semin. Cell Dev. Biol. 2011, 22, 536-542.
165. Tolwani, R.J.; Buckmaster, P.S.; Varma, S.; Cosgaya, J.M.; Wu, Y.; Suri, C.; Shooter, E.M. BDNF overexpression increases dendrite complexity in hippocampal dentate gyrus. Neuroscience 2002, 114, 795-805.
166. Ke, Z.; Yip, S.P.; Li, L.; Zheng, X.-X.; Tong, K.-Y. The effects of voluntary, involuntary, and forced exercises on brain-derived neurotrophic factor and motor function recovery: A rat brain ischemia model. PLoS One 2011, 6, e16643.
167. Ploughman, M.; Windle, V.; MacLellan, C.L.; White, N.; Doré, J.J.; Corbett, D. Brain-derived neurotrophic factor contributes to recovery of skilled reaching after focal ischemia in rats. Stroke 2009, 40, 1490-1495.
168. Zhang, Z.G.; Zhang, L.; Jiang, Q.; Zhang, R.; Davies, K.; Powers, C.; Bruggen, N.; Chopp, M. VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J. Clin. Invest. 2000, 106, 829-838.
169. Parnell, S.E.; Ramadoss, J.; Delp, M.D.; Ramsey, M.W.; Chen, W.-J.A.; West, J.R.; Cudd, T.A. Chronic ethanol increases fetal cerebral blood flow specific to the ethanol-sensitive cerebellum under normoxaemic, hypercapnic and acidaemic conditions: Ovine model. Exp. Physiol. 2007, 92, 933-943.
170. Mayhan, W.G. Responses of cerebral arterioles during chronic ethanol exposure. Am. J. Physiol. 1992, 262, H787-H791.
171. Gleason, C.A.; Iida, H.; Hotchkiss, K.J.; Northington, F.J.; Traystman, R.J. Newborn cerebrovascular responses after first trimester moderate maternal ethanol exposure in sheep. Pediatr. Res. 1997, 42, 39-45.
172. Licht, T.; Goshen, I.; Avital, A.; Kreisel, T.; Zubedat, S.; Eavri, R.; Segal, M.; Yirmiya, R.; Keshet, E. Reversible modulations of neuronal plasticity by VEGF. Proc. Natl. Acad. Sci. USA 2011, 108, 5081-5086.
173. Louboutin, J.-P.; Marusich, E.; Gao, E.; Agrawal, L.; Koch, W.J.; Strayer, D.S. Ethanol protects from injury due to ischemia and reperfusion by increasing vascularity via vascular endothelial growth factor. Alcohol 2012, 46, 441-454.
174. Sun, A.; Chen, Y.; James-Kracke, M.; Wixom, P.; Cheng, Y. Ethanol-induced cell death by lipid peroxidation in PC12 cells. Neurochem. Res. 1997, 22, 1187-1192.
175. Johnsen-Soriano, S.; Bosch-Morell, F.; Miranda, M.; Asensio, S.; Barcia, J.M.; Romá, J.; Monfort, P.; Felipo, V.; Romero, F.J. Ebselen prevents chronic alcohol-induced rat hippocampal stress and functional impairment. Alcohol. Clin. Exp. Res. 2007, 31, 486-492.
176. Liu, J.; Yeo, H.C.; Övervik-Douki, E.; Hagen, T.; Doniger, S.J.; Chu, D.W.; Brooks, G.A.; Ames, B.N. Chronically and acutely exercised rats: Biomarkers of oxidative stress and endogenous antioxidants. J. Appl. Physiol. 2000, 89, 21-28.
177. Radak, Z.; Toldy, A.; Szabo, Z.; Siamilis, S.; Nyakas, C.; Silye, G.; Jakus, J.; Goto, S. The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain. Neurochem. Int. 2006, 49, 387-392.
178. Ogonovszky, H.; Berkes, I.; Kumagai, S.; Kaneko, T.; Tahara, S.; Goto, S.; Radák, Z. The effects of moderate-, strenuous-and over-training on oxidative stress markers, DNA repair, and memory, in rat brain. Neurochem. Int. 2005, 46, 635-640.
179. Harman, D. Aging: A theory based on free radical and radiation chemistry. J. Gerontol. 1956, 11, 298-300.
180. Larsen, P.L. Aging and resistance to oxidative damage in caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 1993, 90, 8905-8909.
181. Marosi, K.; Bori, Z.; Hart, N.; Sárga, L.; Koltai, E.; Radák, Z.; Nyakas, C. Long-term exercise treatment reduces oxidative stress in the hippocampus of aging rats. Neuroscience 2012, 226, 21-28.
182. Cui, L.; Hofer, T.; Rani, A.; Leeuwenburgh, C.; Foster, T.C. Comparison of lifelong and late life exercise on oxidative stress in the cerebellum. Neurobiol. Aging 2009, 30, 903-909.
183. Navarro, A.; Gomez, C.; López-Cepero, J.M.; Boveris, A. Beneficial effects of moderate exercise on mice aging: Survival, behavior, oxidative stress, and mitochondrial electron transfer. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004, 286, R505-R511.
184. Saito, M.; Chakraborty, G.; Hegde, M.; Ohsie, J.; Paik, S.-M.; Vadasz, C.; Saito, M. Involvement of ceramide in ethanol-induced apoptotic neurodegeneration in the neonatal mouse brain. J. Neurochem. 2010, 115, 168-177.
185. Chakraborty, G.; Saito, M.; Shah, R.; Mao, R.-F.; Vadasz, C.; Saito, M. Ethanol triggers sphingosine 1-phosphate elevation along with neuroapoptosis in the developing mouse brain. J. Neurochem. 2012, 121, 806-817.
186. VanDeMark, K.L.; Guizzetti, M.; Giordano, G.; Costa, L.G. Ethanol inhibits muscarinic receptor-induced axonal growth in rat hippocampal neurons. Alcohol. Clin. Exp. Res. 2009, 33, 1945-1955.
187. Sharafi, H.; Rahimi, R. The effect of resistance exercise on p53, caspase-9, and caspase-3 in trained and untrained men. J. Strength Cond. Res. 2012, 26, 1142-1148.
188. Kim, D.-H.; Ko, I.-G.; Kim, B.-K.; Kim, T.-W.; Kim, S.-E.; Shin, M.-S.; Kim, C.-J.; Kim, H.; Kim, K.-M.; Baek, S.-S. Treadmill exercise inhibits traumatic brain injury-induced hippocampal apoptosis. Physiol. Behav. 2010, 101, 660-665.
189. Lee, J.; Cho, J.Y.; Oh, S.D.; Kim, S.M.; Shim, Y.T.; Park, S.; Kim, W.K. Maternal exercise reduces hyperthermia-induced apoptosis in developing mouse brain. Int. J. Hyperthermia 2011, 27, 445-452.
190. Snigdha, S.; Berchtold, N.; Astarita, G.; Saing, T.; Piomelli, D.; Cotman, C.W. Dietary and behavioral interventions protect against age related activation of caspase cascades in the canine brain. PLoS One 2011, 6, e24652.
191. Borg, M.L.; Omran, S.F.; Weir, J.; Meikle, P.J.; Watt, M.J. Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice. J. Physiol. 2012, 590, 4377-4389.
192. Jung, H.L.; Kang, H.Y. Effects of endurance exercise and high-fat diet on insulin resistance and ceramide contents of skeletal muscle in sprague-dawley rats. Korean Diabetes J. 2010, 34, 244-252.
193. Daniels, W.M.U.; Marais, L.; Stein, D.J.; Russell, V.A. Exercise normalizes altered expression of proteins in the ventral hippocampus of rats subjected to maternal separation. Exp. Physiol. 2012, 97, 239-247.
194. Maniam, J.; Morris, M.J. Voluntary exercise and palatable high-fat diet both improve behavioural profile and stress responses in male rats exposed to early life stress: Role of hippocampus. Psychoneuroendocrinology 2010, 35, 1553-1564.
195. Kao, T.; Shumsky, J.S.; Murray, M.; Moxon, K.A. Exercise induces cortical plasticity after neonatal spinal cord injury in the rat. J. Neurosci. 2009, 29, 7549-7557.
196. Tsuji, M.; Aoo, N.; Harada, K.; Sakamoto, Y.; Akitake, Y.; Irie, K.; Mishima, K.; Ikeda, T.; Fujiwara, M. Sex differences in the benefits of rehabilitative training during adolescence following neonatal hypoxia-ischemia in rats. Exp. Neurol. 2010, 226, 285-292.
197. Sim, Y.-J.; Kim, H.; Shin, M.-S.; Chang, H.-K.; Shin, M.-C.; Ko, I.-G.; Kim, K.-J.; Kim, T.-S.; Kim, B.-K.; Rhim, Y.-T.; et al. Effect of postnatal treadmill exercise on c-fos expression in the hippocampus of rat pups born from the alcohol-intoxicated mothers. Brain Dev. 2008, 30, 118-125.
198. Redila, V.A.; Olson, A.K.; Swann, S.E.; Mohades, G.; Webber, A.J.; Weinberg, J.; Christie, B.R. Hippocampal cell proliferation is reduced following prenatal ethanol exposure but can be rescued with voluntary exercise. Hippocampus 2006, 16, 305-311.
199. Helfer, J.L.; Calizo, L.H.; Dong, W.K.; Goodlett, C.R.; Greenough, W.T.; Klintsova, A.Y. Binge-like postnatal alcohol exposure triggers cortical gliogenesis in adolescent rats. J. Comp. Neurol. 2009, 514, 259-271.
200. Rees, D.; Sabia, J. Exercise and adolescent mental health: New evidence from longitudinal data. J. Ment. Health Policy Econ. 2010, 13, 13-25.
201. Brand, S.; Gerber, M.; Beck, J.; Hatzinger, M.; Pühse, U.; Holsboer-Trachsler, E. High exercise levels are related to favorable sleep patterns and psychological functioning in adolescents: A comparison of athletes and controls. J. Adolesc. Health 2010, 46, 133-141.
202. Hopkins, M.E.; Nitecki, R.; Bucci, D.J. Physical exercise during adolescence versus adulthood: Differential effects on object recognition memory and brain-derived neurotrophic factor levels. Neuroscience 2011, 194, 84-94.
203. Terry-McElrath, Y.M.; O'Malley, P.M.; Johnston, L.D. Exercise and substance use among american youth, 1991-2009. Am. J. Prev. Med. 2011, 40, 530-540.
204. Buscemi, J.; Martens, M.P.; Murphy, J.G.; Yurasek, A.M.; Smith, A.E. Moderators of the relationship between physical activity and alcohol consumption in college students. J. Am. Coll. Health 2011, 59, 503-509.
205. Kempermann, G.; Kuhn, H.G.; Gage, F.H. Experience-induced neurogenesis in the senescent dentate gyrus. J. Neurosci. 1998, 18, 3206-3212.
206. Olson, A.K.; Eadie, B.; Ernst, C.; Christie, B.R. Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways. Hippocampus 2006, 16, 250-260.
207. Van Praag, H.; Kempermann, G.; Gage, F.H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 1999, 2, 266-270.
208. Clark, P.J.; Kohman, R.A.; Miller, D.S.; Bhattacharya, T.K.; Haferkamp, E.H.; Rhodes, J.S. Adult hippocampal neurogenesis and c-fos induction during escalation of voluntary wheel running in C57BL/6J mice. Behav. Brain Res. 2010, 213, 246-252.
209. Snyder, J.S.; Glover, L.R.; Sanzone, K.M.; Kamhi, J.F.; Cameron, H.A. The effects of exercise and stress on the survival and maturation of adult-generated granule cells. Hippocampus 2009, 19, 898-906.
210. Kronenberg, G.; Bick-Sander, A.; Bunk, E.; Wolf, C.; Ehninger, D.; Kempermann, G. Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol. Aging 2006, 27, 1505-1513.
211. Fuss, J.; Ben Abdallah, N.M.B.; Vogt, M.A.; Touma, C.; Pacifici, P.G.; Palme, R.; Witzemann, V.; Hellweg, R.; Gass, P. Voluntary exercise induces anxiety-like behavior in adult C57BL/6J mice correlating with hippocampal neurogenesis. Hippocampus 2010, 20, 364-376.
212. Rosenzweig, M.; Bennett, E.; Krech, D. Cerebral effects of environmental complexity and training among adult rats. J. Comp. Physiol. Psychol. 1964, 57, 438-439.
213. Turner, A.M.; Greenough, W.T. Differential rearing effects on rat visual cortex synapses. I. Synaptic and neuronal density and synapses per neuron. Brain Res. 1985, 329, 195-203.
214. Greenough, W.T.; Volkmar, F.R.; Juraska, J.M. Effects of rearing complexity on dendritic branching in frontolateral and temporal cortex of the rat. Exp. Neurol. 1973, 41, 371-378.
215. Mustroph, M.L.; Chen, S.; Desai, S.C.; Cay, E.B.; DeYoung, E.K.; Rhodes, J.S. Aerobic exercise is the critical variable in an enriched environment that increases hippocampal neurogenesis and water maze learning in male C57BL/6J mice. Neuroscience 2012, 219, 62-71.
216. Kobilo, T.; Liu, Q.-R.; Gandhi, K.; Mughal, M.; Shaham, Y.; van Praag, H. Running is the neurogenic and neurotrophic stimulus in environmental enrichment. Learn. Mem. 2011, 18, 605-609.
217. Black, J.E.; Isaacs, K.R.; Anderson, B.J.; Alcantara, A.A.; Greenough, W.T. Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proc. Natl. Acad. Sci. USA 1990, 87, 5568-5572.
218. Kleim, J.A.; Lussnig, E.; Schwarz, E.R.; Comery, T.A.; Greenough, W.T. Synaptogenesis and fos expression in the motor cortex of the adult rat after motor skill learning. J. Neurosci. 1996, 16, 4529-4535.