Exercise, energy intake, glucose homeostasis, and the brain

Journal of Neuroscience

Volumn 34, Issue 46, 2014, Pages 15139-15149

  van Praag, Xhenriette ^a   Fleshner, Monika ^b   Schwartz, Michael W ^c   Mattson, Mark P ^a,d  

^a NATIONAL INSTITUTE ON AGING   (United States)

^b UNIVERSITY OF COLORADO   (United States)

^c UNIVERSITY OF WASHINGTON   (United States)

^d JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINO 4 IMIDAZOLECARBOXAMIDE RIBOSIDE; BRAIN DERIVED NEUROTROPHIC FACTOR; CYTOKINE; HISTONE DEACETYLASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; IMMUNOMODULATING AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; SEROTONIN; GLUCOSE;

ADAPTIVE IMMUNITY; ARTICLE; BRAIN DEVELOPMENT; BRAIN FUNCTION; CALORIC INTAKE; CALORIC RESTRICTION; CELL STRESS; CELLULAR STRESS RESPONSE; CONNECTOME; DEGENERATIVE DISEASE; DENTATE GYRUS; ENERGY METABOLISM; EXERCISE; FOOD DEPRIVATION; GLUCOSE HOMEOSTASIS; HEART RATE; HIPPOCAMPAL CA3 REGION; HUMAN; IMMUNOMODULATION; INSULIN SENSITIVITY; METABOLIC DISORDER; NERVE CELL NETWORK; NERVE CELL PLASTICITY; NERVE POTENTIAL; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PATTERN RECOGNITION; PHYSICAL ACTIVITY; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; SPATIAL ANALYSIS; TREADMILL; VERBAL MEMORY; ANIMAL; BRAIN; DIET RESTRICTION; HOMEOSTASIS; MENTAL STRESS; METABOLISM; MOTOR ACTIVITY; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALS; BRAIN; EXERCISE; FASTING; GLUCOSE; HOMEOSTASIS; HUMANS; MOTOR ACTIVITY; NEUROGENESIS; NEURONAL PLASTICITY; STRESS, PSYCHOLOGICAL;

EID: 84909942603     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.2814-14.2014     Document Type: Article

References (112)

1. Alirezaei M, Kemball CC, Flynn CT, Wood MR, Whitton JL, Kiosses WB (2010) Short-term fasting induces profound neuronal autophagy. Autophagy 6:702–710.CrossRef Medline
2. Amaral DG, Witter MP (1989) The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31: 571–591.CrossRef Medline
3. Amat J, Matus-Amat P, Watkins LR, Maier SF (1998) Escapable and inescapable stress differentially alter extracellular levels of 5-HT in the basolateral amygdala of the rat. Brain Res 812:113–120.CrossRef Medline
4. Amat J, Baratta MV, Paul E, Bland ST, Watkins LR, Maier SF (2005) Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat Neurosci 8:365–371.CrossRef Medline
5. Amat J, Paul E, Zarza C, Watkins LR, Maier SF (2006) Previous experience with behavioral control over stress blocks the behavioral and dorsal raphe nucleus activating effects of later uncontrollable stress: role of the ventral medial prefrontal cortex. J Neurosci 26:13264–13272.CrossRef Medline
6. Arumugam TV, Phillips TM, Cheng A, Morrell CH, Mattson MP, Wan R (2010) Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann Neurol 67:41–52.CrossRef Medline
7. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Cholerton BA, Plymate SR, Fishel MA, Watson GS, Duncan GE, Mehta PD, Craft S (2010) Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer’s disease. J Alzheimers Dis 22:569–579.CrossRef Medline
8. Baratta MV, Lucero TR, Amat J, Watkins LR, Maier SF (2008) Role of the ventral medial prefrontal cortex in mediating behavioral control-induced reduction of later conditioned fear. Learn Mem 15:84–87.CrossRef Medline
9. Bekinschtein P, Oomen CA, Saksida LM, Bussey TJ (2011) Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable? Semin Cell Dev Biol 22:536–542.CrossRef Medline
10. Bernard C (1854) Leçons de Ohysiologie Experimentale Applique’s à la Medecine. Paris: Bailliere
11. Best JD, Kahn SE, Ader M, Watanabe RM, Ni TC, Bergman RN (1996) Role of glucose effectiveness in the determination of glucose tolerance. Diabetes Care 19:1018–1030 Medline
12. Boschloo L, Reeuwijk KG, Schoevers RA, Pennix WJHB (2014) The impact of lifestyle factors on the 2-year course of depressive and/or anxiety disorders. J Affect Disord 159:73–79.CrossRef Medline
13. Bramble DM, Lieberman DE (2004) Endurance running and the evolution of Homo. Nature 432:345–352.CrossRef Medline
14. Brown JD, Siegel JM (1988) Exercise as a buffer of life stress: a prospective study of adolescent health. Health Psychol 7:341–353.CrossRef Medline
15. Bruce-Keller AJ, Umberger G, McFall R, Mattson MP (1999) Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults. Ann Neurol 45:8–15.CrossRef Medline
16. Cai D (2012) One step from prediabetes to diabetes: hypothalamic inflammation? Endocrinology 153:1010–1013.CrossRef Medline
17. Campeau S, Nyhuis TJ, Sasse SK, Kryskow EM, Herlihy L, Masini CV, Babb JA, Greenwood BN, Fleshner M, Day HE (2010) Hypothalamic pituitary adrenal axis responses to low-intensity stressors are reduced after voluntary wheel running in rats. J Neuroendocrinol 22:872–888.CrossRef Medline
18. Cao ZB, Tabata I, Nishizono H (2009) Good maintenance of physical benefits in a 12-month exercise and nutritional intervention by voluntary, home-based exercise: a 6-month follow-up of a randomized controlled trial. J Bone Miner Metab 27:182–189.CrossRef Medline
19. Cheng A, Wan R, Yang JL, Kamimura N, Son TG, Ouyang X, Luo Y, Okun E, Mattson MP (2012) Involvement of PGC-1_ in the formation and maintenance of neuronal dendritic spines. Nat Commun 3:1250.CrossRef Medline
20. Chiarreotto-Ropelle EC, Pauli LS, Katashima CK, Pimentel GD, Picardi PK, Silva VR, de Souza CT, Prada PO, Cintra DE, Carvalheira JB, Ropelle ER, Pauli JR (2013) Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin and leptin signaling in obese rats. AmJ Physiol Endocrinol Metab 305:E649–E659.CrossRef Medline
21. Clark PJ, Brzezinska WJ, Thomas MW, Ryzhenko NA, Toshkov SA, Rhodes JS (2008) Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice. Neuroscience 155:1048–1058.CrossRef Medline
22. Clelland CD, Choi M, Romberg C, Clemenson GD Jr, Fragniere A, Tyers P, Jessberger S, Saksida LM, Barker RA, Gage FH, Bussey TJ (2009) A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325:210–213.CrossRef Medline
23. Creer DJ, Romberg C, Saksida LM, van Praag H, Bussey TJ (2010) Running enhances spatial pattern separation in mice. Proc Natl Acad Sci U S A 107:2367–2372.CrossRef Medline
24. da Silva AA, Tallam LS, Liu J, Hall JE (2006) Chronic antidiabetic and cardiovascular actions of leptin: role of CNS and increased adrenergic activity. AmJ Physiol Regul Integr Comp Physiol 291:R1275–R1282.CrossRef Medline
25. Davis LM, Pauly JR, Readnower RD, Rho JM, Sullivan PG (2008) Fasting is neuroprotective following traumatic brain injury. J Neurosci Res 86: 1812–1822.CrossRef Medline
26. Day HE, Greenwood BN, Hammack SE, Watkins LR, Fleshner M, Maier SF, Campeau S (2004) Differential expression of 5HT-1A, alpha 1b adrenergic, CRF-R1, and CRF-R2 receptor mRNA in serotonergic, gammaaminobutyric acidergic, and catecholaminergic cells of the rat dorsal raphe nucleus. J Comp Neurol 474:364–378.CrossRef Medline
27. Dezfulian C, Garrett M, Gonzalez NR (2013) Clinical application of preconditioning and postconditioning to achieve neuroprotection. Transl Stroke Res 4:19–24.CrossRef Medline
28. Duan W, Mattson MP (1999) Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson’s disease. J Neurosci Res 57:195–206.CrossRef Medline
29. Duan W, Guo Z, Jiang H, Ware M, Li XJ, Mattson MP (2003) Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc Natl Acad Sci U S A 100:2911–2916.CrossRef Medline
30. Duman CH, Schlesinger L, Russell DS, Duman RS (2008) Voluntary exercise produces antidepressant and anxiolytic behavioral effects in mice. Brain Res 1199:148–158.CrossRef Medline
31. Fleshner M (2000) Exercise and neuroendocrine regulation of antibody production: protective effect of physical activity on stress-induced suppression of the specific antibody response. Int J Sports Med 21 [Suppl 1]:S14–S19.
32. Fleshner M (2005) Physical activity and stress resistance: sympathetic nervous system adaptations prevent stress-induced immunosuppression. Exerc Sport Sci Rev 33:120–126.CrossRef Medline
33. Fleshner M, Maier SF, Lyons DM, Raskind MA (2011) The neurobiology of the stress-resistant brain. Stress 14:498–502.CrossRef Medline
34. Fleshner M, Thompson RS, Greenwood BN (2013) Impact of physical activity on diurnal rhythms: a potential mechanisms for stress resistance or stress resilience. In: The handbook of physical activity and mental health. New York: Routledge.
35. Foley TE, Fleshner M (2008) Neuroplasticity of dopamine circuits after exercise: implications for central fatigue. Neuromolecular Med 10:67–80.CrossRef Medline
36. German JP, Thaler JP, Wisse BE, Oh IS, Sarruf DA, Matsen ME, Fischer JD, Taborsky GJ Jr, Schwartz MW, Morton GJ (2011) Leptin activates a novel CNS mechanism for insulin-independent normalization of severe diabetic hyperglycemia. Endocrinology 152:394–404.CrossRef Medline
37. Greenwood BN, Fleshner M (2008) Exercise, learned helplessness, and the stress-resistant brain. Neuromolecular Med 10:81–98.CrossRef Medline
38. Greenwood BN, Fleshner M (2011) Exercise, stress resistance, and central serotonergic systems. Exerc Sport Sci Rev 39:140–149.CrossRef Medline
39. Greenwood BN, Kennedy S, Smith TP, Campeau S, Day HE, Fleshner M (2003a) Voluntary freewheel running selectively modulates catecholamine content in peripheral tissue and c-Fos expression in the central sympathetic circuit following exposure to uncontrollable stress in rats. Neuroscience 120:269–281.CrossRef Medline
40. Greenwood BN, Foley TE, Day HE, Campisi J, Hammack SH, Campeau S, Maier SF, Fleshner M (2003b) Freewheel running prevents learned helplessness/behavioral depression: role of dorsal raphe serotonergic neurons. J Neurosci 23:2889–2898.
41. Medline Greenwood BN, Foley TE, Burhans D, Maier SF, Fleshner M (2005) The consequences of uncontrollable stress are sensitive to duration of prior wheel running. Brain Res 1033:164–178.CrossRef Medline
42. Greenwood BN, Foley TE, Le TV, Strong PV, Loughridge AB, Day HE, Fleshner M (2011) Long-term voluntary wheel running is rewarding and produces plasticity in the mesolimbic reward pathway. Behav Brain Res 217: 354–362.CrossRef Medline
43. Greenwood BN, Loughridge AB, Sadaoui N, Christianson JP, Fleshner M (2012a) The protective effects of voluntary exercise against the behavioral consequences of uncontrollable stress persist despite an increase in anxiety following forced cessation of exercise. Behav Brain Res 233:314–321.CrossRef Medline
44. Greenwood BN, Strong PV, Loughridge AB, Day HE, Clark PJ, Mika A, Hellwinkel JE, Spence KG, Fleshner M (2012b) 5-HT(2C) receptors in the basolateral amygdala and dorsal striatum are a novel target for the anxiolytic and antidepressant effects of exercise. PLoS One 7:e46118.CrossRef Medline
45. Greenwood BN, Spence KG, Crevling DM, Clark PJ, Craig WC, Fleshner M (2013) Exercise-induced stress resistance is independent of exercise controllability and the medial prefrontal cortex. Eur J Neurosci 37:469–478.CrossRef Medline
46. Grégoire CA, Bonenfant D, Le Nguyen A, Aumont A, Fernandes KJ (2014) Untangling the influences of voluntary running, environmental complexity, social housing and stress on adult hippocampal neurogenesis. PLoS One 9:e86237.CrossRef Medline
47. Halagappa VK, Guo Z, Pearson M, Matsuoka Y, Cutler RG, Laferla FM, Mattson MP (2007) Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease. Neurobiol Dis 26:212–220.CrossRef Medline
48. Hardie DG (2004) The AMP-activated protein kinase pathway: new players upstream and downstream. J Cell Sci 117:5479–5487.CrossRef Medline
49. Harvie MN, Pegington M, Mattson MP, Frystyk J, Dillon B, Evans G, Cuzick J, Jebb SA, Martin B, Cutler RG, Son TG, Maudsley S, Carlson OD, Egan JM, Flyvbjerg A, Howell A (2011) The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. J Obes (Lond) 35:714–727.CrossRef Medline
50. Havel PJ, Uriu-Hare JY, Liu T, Stanhope KL, Stern JS, Keen CL, Ahrén B (1998) Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin. AmJ Physiol 274:R1482–R1491.
51. Medline Horvath TL, Sarman B, García-Cáceres C, Enriori PJ, Sotonyi P, Shanabrough M, Borok E, Argente J, Chowen JA, Perez-Tilve D, Pfluger PT, Brönneke HS, Levin BE, Diano S, Cowley MA, Tschöp MH (2010) Synaptic input organization of the melanocortin system predicts dietinduced hypothalamic reactive gliosis and obesity. Proc Natl Acad Sci U S A 107:14875–14880.CrossRef Medline
52. Jeong MA, Plunet W, Streijger F, Lee JH, Plemel JR, Park S, Lam CK, Liu J, Tetzlaff W (2011) Intermittent fasting improves functional recovery after rat thoracic contusion spinal cord injury. J Neurotrauma 28:479–492.CrossRef Medline
53. Johnson JB, Summer W, Cutler RG, Martin B, Hyun DH, Dixit VD, Pearson M, Nassar M, Telljohan R, Maudsley S, Carlson O, John S, Laub DR, Mattson MP (2007) Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med 42:665–674.CrossRef Medline
54. Kahn SE, Cooper ME, Del Prato S (2014) Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 383: 1068–1083.CrossRef Medline
55. Kennedy SL, Smith TP, Fleshner M (2005) Resting cellular and physiological effects of freewheel running. Med Sci Sports Exerc 37:79–83.CrossRef Medline
56. Kobilo T, Yuan C, van Praag H (2011a) Endurance factors improve hippocampal neurogenesis and spatial memory in mice. Learn Mem 18:103–107.CrossRef Medline
57. Kobilo T, Liu QR, Gandhi K, Mughal M, Shaham Y, van Praag H (2011b) Running is the neurogenic and neurotrophic stimulus in environmental enrichment. Learn Mem 18:605–609.CrossRef Medline
58. Kobilo T, Guerrieri D, Zhang Y, Collica SC, Becker KG, van Praag H (2014) AMPK agonist AICAR improves cognition and motor coordination in young and aged mice. Learn Mem 21:119–126.CrossRef Medline
59. Krawczewski Carhuatanta KA, Demuro G, Tschöp MH, Pfluger PT, Benoit SC, Obici S (2011) Voluntary exercise improves high-fat diet-induced leptin resistance independent of adiposity. Endocrinology 152:2655–2664.CrossRef Medline
60. Kuhla B, Kuhla S, Rudolph PE, Albrecht D, Metges CC (2007) Proteomics analysis of hypothalamic response to energy restriction in dairy cows. Proteomics 7:3602–3617.CrossRef Medline
61. Lee J, Duan W, Mattson MP (2002) Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 82:1367–1375.CrossRef Medline
62. Lett BT, Grant VL, Byrne MJ, Koh MT (2000) Pairings of a distinctive chamber with the aftereffect of wheel running produce conditioned place preference. Appetite 34:87–94.CrossRef Medline
63. Lett BT, Grant VL, Koh MT (2001) Naloxone attenuates the conditioned place preference induced by wheel running in rats. Physiol Behav 72:355–358.CrossRef Medline
64. Li L, Wang Z, Zuo Z (2013) Chronic intermittent fasting improves cognitive functions and brain structures in mice. PLoS One 8:e66069.CrossRef Medline
65. Li Y, Luikart BW, Birnbaum S, Chen J, Kwon CH, Kernie SG, Bassel-Duby R, Parada LF (2008) TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron 59:399–412.CrossRef Medline
66. Longo VD, Mattson MP (2014) Fasting: molecular mechanisms and clinical applications. Cell Metab 19:181–192.CrossRef Medline
67. Loughridge AB, Greenwood BN, Day HE, McQueen MB, Fleshner M (2013) Microarray analyses reveal novel targets of exercise-induced stress resistance in the dorsal raphe nucleus. Front Behav Neurosci 7:37.CrossRef Medline
68. Lu M, Wan M, Leavens KF, Chu Q, Monks BR, Fernandez S, Ahima RS, Ueki K, Kahn CR, Birnbaum MJ (2012) Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. Nat Med 18:388–395.CrossRef Medline
69. Madorsky I, Opalach K, Waber A, Verrier JD, Solmo C, Foster T, Dunn WA Jr, Notterpek L (2009) Intermittent fasting alleviates the neuropathic phenotype in a mouse model of Charcot-Marie-Tooth disease. Neurobiol Dis 34:146–154.CrossRef Medline
70. Maier SF, Watkins LR (2010) Role of the medial prefrontal cortex in coping and resilience. Brain Res 1355:52–60.CrossRef Medline
71. Marosi K, Mattson MP (2014) BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab 25:89–98.CrossRef Medline
72. Marr D (1971) Simple memory: a theory for archicortex. Philos Trans R Soc Lond B Biol Sci 262:23–81.CrossRef Medline
73. Mattson MP (2012) Exercise and energy intake as determinants of brain health and vulnerability to injury and disease. Cell Metab 16:706 –722. Meijer JH, Robbers Y (2014) Wheel running in the wild. Proc Biol Soc 281: 1786.CrossRef Medline
74. Milanski M, Arruda AP, Coope A, Ignacio-Souza LM, Nunez CE, Roman EA, Romanatto T, Pascoal LB, Caricilli AM, Torsoni MA, Prada PO, Saad MJ, Velloso LA (2012) Inhibition of hypothalamic inflammation reverses diet-induced insulin resistance in the liver. Diabetes 61:1455–1462.CrossRef Medline
75. Moraska A, Fleshner M (2001) Voluntary physical activity prevents stressinduced behavioral depression and anti-KLH antibody suppression. AmJ Physiol Regul Integr Comp Physiol 281:R484–R489.
76. Medline Morris RG, Garrud P, Rawlins JN, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 24:681–683.CrossRef Medline
77. Morton GJ, Matsen ME, Bracy DP, Meek TH, Nguyen HT, Stefanovski D, Bergman RN, Wasserman DH, Schwartz MW (2013) FGF19 action in the brain induces insulin-independent glucose lowering. J Clin Invest 123:4799–4808.CrossRef Medline
78. Mustroph ML, Chen S, Desai SC, Cay EB, DeYoung EK, Rhodes JS (2012) Aerobic exercise is the critical variable in an enriched environment that increases hippocampal neurogenesis and water maze learning in male C57BL/6J mice. Neuroscience 219:62–71.CrossRef Medline
79. Nakagawa T, Tsuchida A, Itakura Y, Nonomura T, Ono M, Hirota F, Inoue T, Nakayama C, Taiji M, Noguchi H (2000) Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Diabetes 49:436–444.CrossRef Medline
80. Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM (2008) AMPK and PPARδ agonists are exercise mimetics. Cell 134:405–415.CrossRef Medline
81. Neeper SA, Gómez-Pinilla F, Choi J, Cotman C (1995) Exercise and brain neurotrophins. Nature 373:109.CrossRef Medline
82. O’Neill HM (2013) AMPK and exercise: glucose uptake and insulin sensitivity. Diabetes Metab J 37:1–21.CrossRef Medline
83. Page KA, Williamson A, Yu N, McNay EC, Dzuira J, McCrimmon RJ, Sherwin RS (2009) Medium-chain fatty acids improve cognitive function in intensively treated type 1 diabetic patients and support in vitro synaptic transmission during acute hypoglycemia. Diabetes 58:1237–1244.CrossRef Medline
84. Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA (2007) An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A 104:5638–5643.CrossRef Medline
85. Philippas NG, Lo CW (2005) Childhood obesity: etiology, prevention, and treatment. Nutr Clin Care 8:77–88.
86. Medline Pi-Sunyer X (2009) The medical risks of obesity. Postgrad Med 121:21–33.CrossRef Medline
87. Posey KA, Clegg DJ, Printz RL, Byun J, Morton GJ, Vivekanandan-Giri A, Pennathur S, Baskin DG, Heinecke JW, Woods SC, Schwartz MW, Niswender KD (2009) Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet. Am J Physiol Endocrinol Metab 296:E1003–E1012.CrossRef Medline
88. Sahay A, Scobie KN, Hill AS, O’Carroll CM, Kheirbek MA, Burghardt NS, Fenton AA, Dranovsky A, Hen R (2011) Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472:466–470.CrossRef Medline
89. Sasse SK, Greenwood BN, Masini CV, Nyhuis TJ, Fleshner M, Day HE, Campeau S (2008) Chronic voluntary wheel running facilitates corticosterone response habituation to repeated audiogenic stress exposure in male rats. Stress 11:425–437.CrossRef Medline
90. Schmidt-Kassow M, Deusser M, Thiel C, Otterbein S, Montag C, Reuter M, Banzer W, Kaiser J (2013) Physical exercise during encoding improves vocabulary learning in young female adults: a neuroendocrinological study. PLoS One 8:e64172.CrossRef Medline
91. Schwartz MW, Seeley RJ, Tscho¨p MH, Woods SC, Morton GJ, Myers MG, D’Alessio D (2013) Cooperation between brain and islet in glucose homeostasis and diabetes. Nature 503:59–66.CrossRef Medline
92. Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV Jr, de Cabo R, Ulrich S, Akassoglou K, Verdin E (2013) Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339:211–214.CrossRef Medline
93. Speaker KJ, Cox SS, Paton MM, Serebrakian A, Maslanik T, Greenwood BN, Fleshner M (2014) Six weeks of voluntary wheel running modulates inflammatory protein (MCP-1, IL-6, and IL-10) and DAMP (Hsp72) responses to acute stress in white adipose tissue of lean rats. Brain Behav Immun 39:87–98.CrossRef Medline
94. Stranahan AM, Lee K, Martin B, Maudsley S, Golden E, Cutler RG, Mattson MP (2009) Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice. Hippocampus 19:951–961.CrossRef Medline
95. Stranahan AM, Lee K, Becker KG, Zhang Y, Maudsley S, Martin B, Cutler RG, Mattson MP (2010) Hippocampal gene expression patterns underlying the enhancement of memory by running in aged mice. Neurobiol Aging 31:1937–1949.CrossRef Medline
96. Strong PV, Greenwood BN, Fleshner M (2009) The effects of the selective 5-HT(2C)receptor antagonistSB242084onlearned helplessness in male Fischer 344 rats. Psychopharmacology (Berl) 203:665–675.CrossRef Medline
97. Strong PV, Christianson JP, Loughridge AB, Amat J, Maier SF, Fleshner M, Greenwood BN (2011) 5-Hydroxytryptamine 2C receptors in the dorsal striatum mediate stress-induced interference with negatively reinforced instrumental escape behavior. Neuroscience 197:132–144.CrossRef Medline
98. Taupin P (2007) Adult neural stem cells: The promise of the future. Neuropsychiatr Dis Treat. 3:753–760.
99. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschöp MH, Schwartz MW (2012) Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122:153–162.CrossRef Medline
100. Thompson RS, Strong PV, Clark PJ, Maslanik TM, Wright KP Jr, Greenwood BN, Fleshner M (2014) Repeated fear-induced diurnal rhythm disruptions predict PTSD-like sensitized physiological acute stress responses in F344 rats. Acta Physiol 211:447–465.CrossRef Medline
101. Tong L, Shen H, Perreau VM, Balazs R, Cotman CW (2001) Effects of exercise on gene-expression profile in the rat hippocampus. Neurobiol Dis 8:1046–1056.CrossRef Medline
102. van Praag H (2008) Neurogenesis and exercise: past and future directions. Neuromolecular Med 10:128–140.CrossRef Medline
103. Vivar C, Potter MC, Choi J, Lee JY, Stringer TP, Callaway EM, Gage FH, Suh H, van Praag H (2012) Monosynaptic inputs to new neurons in the dentate gyrus. Nat Commun 3:1107. doi: 10.1038/ncomms2101.CrossRef Medline
104. Vivar C, Potter MC, van Praag H (2013) All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis. Curr Top Behav Neurosci 15:189–210.CrossRef Medline
105. Voss MW, Vivar C, Kramer AF, van Praag H (2013) Bridging animal and human models of exercise-induced brain plasticity. Trends Cogn Sci 17: 525–544.CrossRef Medline
106. Wan R, Weigand LA, Bateman R, Griffioen K, Mendelowitz D, Mattson MP(2014) Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability. J Neurochem 129:573–580.CrossRef Medline
107. Wang YX, Zhang CL, Yu RT, Cho HK, Nelson MC, Bayuga-Ocampo CR, Ham J, Kang H, Evans RM (2004) Regulation of muscle fiber type and running endurance by PPARδ. PLoS Biol 2:e294.CrossRef Medline
108. Witte AV, Fobker M, Gellner R, Knecht S, Flöel A (2009) Caloric restriction improves memory in elderly humans. Proc Natl Acad SciU S A106:1255–1260.CrossRef Medline
109. Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, Lin JD, Greenberg ME, Spiegelman BM (2013) Exercise induces hippocampal BDNF throughaPGC-1α/FNDC5pathway. CellMetab 18: 649–659CrossRefMedline
110. Xu X, Zhan M, Duan W, Prabhu V, Brenneman R, Wood W, Firman J, Li H, Zhang P, Ibe C, Zonderman AB, Longo DL, Poosala S, Becker KG, Mattson MP (2007) Gene expression atlas of the mouse central nervous system: impact and interactions of age, energy intake and gender. Genome Biol 8:R234.CrossRef Medline
111. Yang JL, Lin YT, Chuang PC, Bohr VA, Mattson MP (2014) BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1. Neuromolecular Med 16:161–174.CrossRef Medline
112. Zammit GK, Ackerman SH, Shindledecker R, Fauci M, Smith GP (1992) Postprandial sleep and thermogenesis in normal men. Physiol Behav 52: 251–259.CrossRef Medline