State of the art of the neurotrophin hypothesis in psychiatric disorders: Implications and limitations

Journal of Neural Transmission

Volumn 111, Issue 3, 2004, Pages 387-411

  Lang, U E ^a   Jockers Scherubl M C ^a   Hellweg, R ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Alzheimer's disease; BDNF; Brain derived neurotrophic factor; Depression; Nerve growth factor; Neurotrophin 3; NGF; NT 3; Schizophrenia; Stress

Indexed keywords

ANTIDEPRESSANT AGENT; BRAIN DERIVED NEUROTROPHIC FACTOR; BRAIN DERIVED NEUROTROPHIC FACTOR RECEPTOR; CLOZAPINE; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; HALOPERIDOL; NERVE GROWTH FACTOR; NERVE GROWTH FACTOR RECEPTOR; NEUROLEPTIC AGENT; NEUROTROPHIN; NEUROTROPHIN 3; NEUROTROPHIN 3 RECEPTOR; NEUROTROPHIN 4; NEUROTROPHIN 6; OLANZAPINE; PROTEIN TYROSINE KINASE; RISPERIDONE; RITANSERIN; SEROTONIN 2 ANTAGONIST;

ALZHEIMER DISEASE; BRAIN ATROPHY; BRAIN REGION; CELL LOSS; COGNITIVE DEFECT; DEGENERATIVE DISEASE; DEPRESSION; DRUG EFFECT; ELECTROCONVULSIVE THERAPY; EMOTIONAL DISORDER; GENE EXPRESSION; HISTOPATHOLOGY; HUMAN; MENTAL DISEASE; MOOD DISORDER; NERVE CELL PLASTICITY; NEUROPROTECTION; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SECRETION; REVIEW; RISK FACTOR; SCHIZOPHRENIA; STRESS; SYNAPTIC TRANSMISSION;

ALZHEIMER DISEASE; ANIMALS; DEPRESSION; HUMANS; MENTAL DISORDERS; MODELS, NEUROLOGICAL; MULTIGENE FAMILY; NERVE GROWTH FACTORS; RISK FACTORS; SCHIZOPHRENIA; STRESS;

EID: 1542373546     PISSN: 03009564     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00702-003-0100-0     Document Type: Review

References (180)

1. Alleva E, Santucci D (2001) Psychosocial vs. "physical" stress situations in rodents and humans: role of neurotrophins. Physiol Behav 73: 313-320
2. Alleva E, Della Seta D, Cirulli F, Aloe L (1996) Haloperidol treatment decreases nerve growth factor levels in the hypothalamus of adult mice. Prog Psychopharmacol Biol Psychiatry 20: 483-489
3. Aloe L, Bracci-Laudiero L, Alleva A, Lambiase A, Micera A, Tirassa P (1994) Emotional stress induced by parachute jumping enhances blood nerve growth factor levels and distribution of nerve growth factor receptors in lymphocytes. Proc Natl Acad Sci USA 91: 10440-10444
4. Aloe L, Iannitelli A, Bersani G, Alleva E, Angelucci F, Maselli P, Manni L (1997) Haloperidol administration in humans lowers plasma nerve growth factor level: evidence that sedation induces opposite effects to arousal. Pharmacopsych 36: 65-68
5. Altar CA (1999) Neurotrophins and depression. Trends Pharmacol Sci 20: 59-61
6. Altar CA, Distefano PS (1998) Neurotrophin trafficking by anterograde transport. Trends Neurosci 21: 433-437
7. Amoureux MC, Van Gool D, Herrero MT, Dom R, Colpaert FC, Pauwels PJ (1997) Regulation of metallothionein-III (GIF) mRNA in the brain of patients with Alzheimer's disease is not impaired. Mol Chem Neuropathol 32: 101-121
8. Angelucci F, Mathe AA, Aloe L (2000) Brain-derived neurotrophic factor and tyrosine kinase receptor TrkB in rat brain are significantly altered after haloperidol and risperidone administration. J Neurosci Res 60: 783-794
9. Angelucci F, Aloe L, Jimenez-Vasquez P, Mathe AA (2003) Electroconvulsive stimuli alter nerve growth factor but not brain-derived neurotrophic factor concentrations in brains of a rat model of depression. Neuropeptides 37: 51-56
10. Barbacid M (1995) Neurotrophic factors and their receptors. Curr Opin Cell Biol 7: 148-155
11. Beck T, Lindholm D, Castren E, Wree A (1994) Brain-derived neurotrophic factor protects against ischemic cell damage in rat hippocampus. J Cereb Blood Flow Metab 14: 689-692
12. Bersani G, Iannitelli A, Maselli P, Pancheri P, Aloe L, Angelucci F, Alleva E (1999) Low nerve growth factor plasma levels in schizophrenic patients: a preliminary study. Schizophr Res 37: 201-203
13. Chao MV, Bothwell M (2002) Neurotrophins: to cleave or not to cleave. Neuron 33: 9-12
14. Chen KS, Nishimura MC, Armanini MP, Crowley C, Spencer SD, Phillips HS (1997) Disruption of a single allele of the nerve growth factor gene results in atrophy of basal forebrain cholinergic neurons and memory deficits. J Neurosci 17: 7288-7296
15. Chen B, Dowlatshahi D, MacQueen GM, Wang JF, Young LT (2001) Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 50: 260-265
16. Chlan-Fourney J, Ashe P, Nylen K, Juorio AV, Li XM (2002) Differential regulation of hippocampal BDNF mRNA by typical and atypical antipsychotic administration. Brain Res 954: 11-20
17. Chourbaji S, Hellweg R, Brandis D, Zörner B, Zacher C, Lang UE, Henn FA, Hörtnagl H, Gass P (2004) Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior. Mol Brain Res (in press)
18. Connor B, Young D, Yan Q, Faull RLM, Syenek B, Dragaunow M (1997) Brain-derived neurotrophic factor is reduced in Alzheimer's disease. Mol Brain Res 49: 71-81
19. Conti AC, Cryan JF, Dalvi A, Lucki I, Blendy JA (2002) cAMP response element-binding protein is essential for the upregulation of brain-derived neurotrophic factor transcription, but not the behavioural or endocrine responses to antidepressant drugs. J Neurosci 22: 3262-3268
20. Croll SD, Ip NY, Lindsay RM, Wiegand SJ (1998) Expression of BDNF and trk B as a function of age and cognitive performance. Brain Res 812: 200-208
21. Crutcher KA, Scott SA, Liang S, Everson WV, Weingartner J (1993) Detection of NGF-like activity in human brain tissue: increased levels in Alzheimer's disease. J Neurosci 13: 2540-2550
22. Dawson E, Powell JF, Sham PC, Nothen M, Crocq MA, Propping P, Korner J, Rietschel M, van Os J, Wright P (1995) An association study of a neurotrophin-3 (NT-3) gene polymorphism with schizophrenia. Acta Psychiatr Scand 92: 425-428
23. Dawson NM, Hamid EH, Egan MF, Meredith GE (2001) Changes in the pattern of brain-derived neurotrophic factor immunoreactivity in the rat brain after acute and subchronic haloperidol treatment. Synapse 39: 70-81
24. Dechant G, Neumann G (2002) Neurotrophins. Adv Exp Med Biol 513: 303-334
25. Desai NS, Rutherford LC, Turrigiano GG (1999) BDNF regulates the intrinsic excitability of cortical neurons. Learn Mem 6: 284-291
26. Duinkerk SJ, Botter PA, Jansen AA, van Dongen PA, van Haaften AJ, Boom AJ, van Laarhoven JH, Busard HL (1993) Ritanserin, a selective 5-HT2/1C antagonist, and negative symptoms in schizophrenia. A placebo-controlled double-blind trial. Br J Psychiatry 163: 451-455
27. Duman RS, Vaidya VA (1998) Molecular and cellular actions of chronic electroconvulsive seizures. J ECT 14: 181-193
28. Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54: 597-606
29. Duman RS, Malberg J, Nakagawa S, D'Sa C (2000) Neuronal plasticity and survival in mood disorders. Biol Psychiatry 15: 732-739
30. Durany N, Michel T, Kurt J, Cruz-Sanchez FF, Cervos-Navarro J, Riederer P (2000) Brain-derived neurotrophic factor and neurotrophin-3 level in Alzheimer's disease brains. Int J Dev Neurosci 18: 807-813
31. Durany N, Michel T, Zochling R, Boissl KW, Cruz-Sanchez FF, Riederer P, Thome J (2001) Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses. Schizophr Res 52: 79-86
32. Everitt BJ, Robbins TW (1997) Central cholinergic systems and cognition. Annu Rev Psychol 48: 649-684
33. Fahnestock M, Garzon D, Holsinger RMD, Michalski B (2002) Neurotrophic factors and Alzheimer's disease: are we focusing on the wrong molecule? J Neural Transm [Suppl] 62: 241-252
34. Ferrer I, Marin C, Rey MJ, Ribalta T, Goutan E, Blanco R, Tolosa E, Marti E (1999) BDNF and full-length and truncated TrkB expression in Alzheimer's disease. Implications in therapeutic strategies. J Neuropathol Exp Neurol 58: 729-739
35. Finkbeiner S (2000) CREB couples neurotrophin signals to survival messages. Neuron 25: 11-14
36. Finkelstein Y, Koffler B, Rabey J, Gilad G (1985) Dynamics of the cholinergic synaptic mechanism in the rat hippocampus after stress. Brain Res 343: 314-319
37. Fischer W, Wictorin K, Bjorklund A, Williams LR, Varon S, Gage FH (1987) Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor. Nature 329: 65-68
38. Foreman PJ, Taglialatela G, Angelucci L, Turner CP, Perez-Polo JR (1993) Nerve growth factor and p75 NGFR factor mRNA change in rodent CNS following stress activation of the hypothalamo-pituitary adrenocortical axis. J Neurosci 6: 10-18
39. Friedman WJ, Greene LA (1999) Neurotrophin signaling via Trks and p75. Exp Cell Res 253: 131-142
40. Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi J, Sun B, Tandon NN (2002) Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 87: 728-734
41. Gage FH, Wolff JA, Rosenberg MB, Xu L, Yee JK, Shults C, Friedman T (1987) Grafting genetically modified cells to the brain: possibilities for the future. Neuroscience 23: 795-807
42. Garcia R (2002) Stress, metaplasticity, and antidepressants. Curr Mol Med 2: 629-638
43. Gilmore JH, Jarskog LF, Lindgren JC, McEvoy JP, Xiao H (1997) Neurotrophin-3 levels in the cerebrospinal fluid of patients with schizophrenia or medical illness. Psychiatry Res 73: 109-113
44. Guillin O, Diaz J, Carroll P, Griffon N, Schwartz JC, Sokoloff P (2001) BDNF controls dopamine D3 receptor expression and triggers behavioural sensitisation. Nature 411: 86-89
45. Hadjiconstantinou M, McGuire L, Duchemin A, Laskowski B, Kiecolt-Glaser J, Glaser R (2001) Changes of nerve growth factor levels in older adults associated with chronic stress. J Neuroimmunol 166: 102-106
46. Hall J, Thomas KL, Everitt BJ (2000) Rapid and selective induction of BDNF expression in the hippocampus during contextual learning. Nat Neurosci 3: 533-535
47. Hardy J (1997) Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci 20: 154-159
48. Harrison PJ (1999) The neuropathology of schizophrenia: a critical review of the data and their interpretation. Brain 122: 593-624
49. Hattori M, Nanko S (1995) Association of neurotrophin-3 gene variant with severe forms of schizophrenia. Biochem Biophys Res Commun 209: 513-518
50. Hattori M, Kunugi H, Akahane A, Tanaka H, Ishida S, Hirose T, Morita R, Yamakawa K, Nanko S (2002) Novel polymorphisms in the promoter region of the neurotrophin-3 gene and their associations with schizophrenia. Am J Med Genet 114: 304-309
51. Hecker S, Mesulam MM (1994) Two types of cholinergic projections to the rat amygdala. Neuroscience 60: 383-397
52. Hefti F (1994) Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections. J Neurosci 6: 2155-2162
53. Hellweg R, Humpel C, Löwe A, Hörtnagl H (1997) Moderate lesion of the rat cholinergic septohippocampal pathway increases hippocampal nerve growth factor synthesis: evidence for long-term compensatory changes? Mol Brain Res 45: 177-181
54. Hellweg R, Gericke CA, Jendroska K, Hartung HD, Cervos-Navarro J (1998a) NGF content in the cerebral cortex of non-demented patients with amyloid-plaques and in symptomatic Alzheimer's disease. Int J Dev Neurosci 16: 787-794
55. Hellweg R, v Richthofen S, Anders D, Baethge C, Röpke S, Hartung HD, Gericke C (1998b) The time course of nerve growth factor content in different neuropsychiatric diseases: a unifying hypothesis. J Neural Transm 105: 871-903
56. Hellweg R, Lang UE, Nagel M, Baumgartner A (2002) Subchronic treatment with lithium increases nerve growth factor content in distinct brain regions of adult rats. Mol Psychiatry 7: 604-608
57. Hellweg R, von Arnim CAF, Büchner M, Huber R, Riepe MW (2003) Neuroprotection and neuronal dysfunction upon repetitive inhibition of oxidative phosphorylation. Exp Neurol 183: 346-354
58. Herman JP, Cullinan WE (1997) Neurocircuitry of stress: central control of the hypothalamic-pituitary-adrenocortical axis. Trends Neurosci 20: 78-84
59. Hock C, Heese K, Müller-Spahn F, Hulette C, Rosenberg C, Otten U (1998) Decreased trkA neurotrophin receptor expression in the parietal cortex of patients with Alzheimer's disease. Neurosci Lett 241: 151-154
60. Hock C, Heese K, Hulette C, Rosenberg C, Otten U (2000a) Region-specific neurotrophin imbalances in Alzheimer's disease: decreased levels of BDNF and increased levels of NGF in hippocampus and cortical areas. Arch Neurol 57: 846-851
61. Hock C, Heese K, Müller-Spahn F, Huber P, Riesen W, Nitsch RM, Otten U (2000b) Increased cerebrospinal fluid levels of neurotrophin 3 (NT-3) in elderly patients with major depression. Mol Psychiatry 5: 510-513
62. Hock C, Heese K, Müller-Spahn F, Huber P, Riesen W, Nitsch RM, Otten U (2000c) Increased CSF levels of nerve growth factor in patients with Alzheimer's disease. Neurology 54: 2009-2011
63. Hörtnagl H, Hellweg R (1997) Insights into the role of the cholinergic component of the septohippocampal pathway: what have we learned from experimental lesion studies? Brain Res Bull 43: 245-255
64. Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350: 230-232
65. Imperato A, Puglisi-Allegra S, Casolini P, Angelucci L (1991) Changes in brain dopamine and acetylcholine release during and following stress are independent of the pituitary-adrenocortical axis. Brain Res 538: 111-117
66. Jankowsky JL, Patterson PH (1999) Cytokine and growth factor involvement in long-term potentiation. Mol Cell Neurosci 14: 273-286
67. Jensen J, Mikkelsen J, Mørk A (2000) Increased adenylyl cyclase type 1 mRNA, but not adenylyl cyclase type 2 in the rat hippocampus following antidepressant treatment. Eur Neuropsychopharmacol 10: 105-111
68. Jockers-Scherübl M, Matthies U, Danker-Hopfe H, Lang UE, Mahlberg R, Hellweg R (2003) Chronic cannabis abuse raises nerve growth factor serum concentrations in drug-naive schizophrenic patients. J Psychopharmacol 17: 429-435
69. Jonsson E, Brene S, Zhang XR, Nimgaonkar VL, Tylec A, Schalling M, Sedvall G (1997) Schizophrenia and neurotrophin-3 alleles. Acta Psychiatr Scand 95: 414-419
70. Kang H, Schuman EM (1995) Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science 267: 1658-1662
71. Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM (2002a) Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 109: 143-148
72. Karege F, Schwald M, Cisse M (2002b) Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci Lett 328: 261-264
73. Klyushnik TP, Turkova IL, Danilovskaya EV, Kozlova IA, Bashina VM, Simashkova NV, Babishchevich NK (2000) Correlation between levels of autoantibodies to nerve growth factor and the clinical features of schizophrenia in children. Neurosci Behav Physiol 30: 119-121
74. Knipper M, Da Penha Berzachi M, Blöchl A, Breer H, Thoenen H, Lindholm D (1994) Positive feedback between actylcholine and neurotropins nerve growth factor and brain derived neurotrophic factor in the rat hippocampus. Eur J Neurosci 6: 668-671
75. Koliatsos VE, Nauta HJ, Clatterbuck RE, Holtzman DM, Mobley WC, Price DL (1990) Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkeys. J Neurosci 10: 3801-3813
76. Korsching S, Auburger G, Heumann R, Scott J, Thoenen H (1985) Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. EMBO J 4: 1389-1393
77. Krebs MO, Guillin O, Bourdell MC, Schwartz JC, Olie JP, Poirier MF, Sokoloff P (2000) Brain derived neurotrophic factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia. Mol Psychiatry 5: 558-562
78. Kromer LF (1987) Nerve growth factor treatment after brain injury prevents neuronal death. Science 235: 214-216
79. Kunugi H, Ueki A, Otsuka M, Isse K, Hirasawa H, Kato N, Nabika T, Kobayashi S, Nanko S (2001) A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer's disease. Mol Psychiatry 6: 83-86
80. Lang UE, Gallinat J, Kuhn S, Jockers-Scherübl MC, Hellweg R (2002) Nerve growth factor and smoking cessation. Am J Psychiatry 159: 674-675
81. Lang UE, Gallinat J, Danker-Hopfe H, Bajbouj M, Hellweg R (2003) Nerve growth factor serum concentrations in healthy human volunteers: physiological variance and stability. Neurosci Lett 344: 13-16
82. Lang UE, Anders D, Danker-Hopfe H, Hellweg R (2004) Measurement of nerve growth factor serum concentration in a psychologically stressful situation in men. Stress (in press)
83. Levi-Montalcini R (1987) The nerve growth factor 35 years later. Science 237: 1154-1162
84. Levi-Montalcini R, Skaper SD, Dal Toso R, Petrelli L, Leon A (1996) Nerve growth factor: from neurotrophin to neurokine. Trends Neurosci 19: 514-520
85. Lewin GR, Barde YA (1996) Physiology of neurotrophins. Annu Rev Neurosci 19: 289-317
86. Lewis DA, Gonzalez-Burgos G (2000) Intrinsic excitatory connections in the prefrontal cortex and the pathophysiology of schizophrenia. Brain Res Bull 52: 309-317
87. Linden AM, Vaisanen J, Lakso M, Nawa H, Wong G, Castren E (2000) Expression of neurotrophins BDNF and NT-3, and their receptors in rat brain after administration of antipsychotic and psychotrophic agents. J Mol Neurosci 14: 27-37
88. Lindholm D, Dechant G, Heisenberg CP, Thoenen H (1993) Brain-derived neurotrophic factor is a survival factor for cultured rat cerebellar granule neurons and protects them against glutamate-induced neurotoxicity. Eur J Neurosci 5: 1455-1464
89. Linnarsson S, Björklund A, Ernfors P (1997) Learning deficit in BDNF mutant mice. Eur J Neurosci 9: 2581-2587
90. Lipska BK, Khaing ZZ, Weickert CS, Weinberger DR (2001) BDNF mRNA expression in rat hippocampus and prefrontal cortex: effects of neonatal ventral hippocampal damage and antipsychotic drugs. Eur J Neurosci 14: 135-144
91. Liu D, Diorio J, Day JC, Francis DD, Meaney MJ (2000) Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat Neurosci 3: 799-806
92. Lu B, Figurov A (1997) Role of neurotrophins in synapse development and plasticity. Rev Neurosci 8: 1-12
93. Maestripieri D, De Simone R, Aloe L, Alleva E (1990) Social status and nerve growth factor serum levels after agonistic encounters in mice. Physiol Behav 47: 161-164
94. Mahadik SP, Parikh V, Khan MM, Buckley PF (2002) Differential effects of antipsychotics on nerve growth factor in rat brain. NCDEU Meeting Abstracts, Session II-8
95. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20: 9104-9110
96. Mamounas LA, Blue ME, Siuciak JA, Altar CA (1995) Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain. J Neurosci 15: 7929-7939
97. Manji HK, Quiroz JA, Sporn J, Payne JL, Denicoff K, Gray AN, Zarate CA Jr, Charney DS (2003) Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry 53: 707-742
98. Marinelli L, Cammarata S, Nobbio L, Schenone A, Zaccheo D, Angelini G, Tabaton M (1999) Tyrosine kinase A-nerve growth factor receptor is antigenically present in dystrophic neuntes from a variety of conditions but not in Alzheimer's disease. Neurosci Lett 273: 67-71
99. Marty S, Berzaghi MP, Berninger B (1997) Neurotrophins and activity-dependent plasticity of cortical interneurons. Trends Neurosci 20: 198-202
100. Mattson MP, Zhang Y, Bose S (1993) Growth factors prevent mitochondrial dysfunction, and cell injury, but not ATP depletion in hippocampal neurons deprived of glucose. Exp Neurol 121: 1-13
101. 2+ concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. J Neurochem 65: 1740-1751
102. McEwen BS (2000) The neurobiology of stress: from serendipity to clinical relevance. Brain Res 886: 172-189
103. Michalski B, Fahnestock M (2003) Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer's disease. Mol Brain Res 111: 148-154
104. Miller FD, Kaplan DR (2001) On trk for retrograde signaling. Neuron 32: 767-770
105. Mohammed AK, Winblad B, Ebendal T, Larkfors L (1990) Environmental influence on behavior and nerve growth factors in the brain. Brain Res 528: 62-72
106. Morcuende S, Gadd CA, Peters M, Moss A, Harris EA, Sheasby A, Fisher AS, de Felipe C, Mantyh PW, Rupniak NMF, Giese KP, Hunt SP (2003) Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice. Eur J Neurosci 18: 1828-1836
107. Mössner R, Daniel S, Albert D, Heils A, Okladnova O, Schmitt A, Lesch KP (2000) Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF). Neurochem Int 36: 197-202
108. Mufson EJ, Lavine N, Jaffar S, Kordower JH, Quirion R, Saragovi HU (1997) Reduction in p140-TrkA receptor protein within the nucleus basalis and cortex in Alzheimer's disease. Exp Neurol 146: 91-103
109. Nakahashi T, Fujimura H, Altar CA, Li J, Kambayashi J, Tandon NN, Sun B (2000) Vascular endothelial cells synthesize and secrete brain-derived neurotrophic factor. FEBS Lett 470: 113-117
110. Narisawa-Saito M, Wakabayashi K, Tsuji S, Takahashi H, Nawa H (1996) Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer's disease. Neuroreport 7: 2925-2928
111. Nestler E, Terwilliger R, Duman R (1989) Chronic antidepressant administration alters the subcellular distribution of cyclic AMP-dependent protein kinase in rat frontal cortex. J Neurochem 53: 1644-1647
112. Neves-Pereira M, Mundo E, Muglia P, King N, Macciardi F, Kennedy JL (2002) The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. Am J Hum Genet 71: 651-655
113. Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15: 7539-7547
114. Nibuya M, Nestler EJ, Duman RS (1996) Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 16: 2365-2372
115. Nibuya M, Takahashi M, Russell DS, Duman RS (1999) Repeated stress increases catalytic TrkB mRNA in rat hippocampus. Neurosci Lett 267: 81-84
116. Obara Y, Nakahata N (2002) The signalling pathway of neurotrophic factor biosynthesis. Drug News Perspect 15: 290-298
117. Otten U, Baumann JB, Girard J (1979) Stimulation of the pituitary-adrenocortical axis by nerve growth factor. Nature 282: 413-414
118. Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ (1998a) Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 37: 1553-1561
119. Pan W, Banks WA, Kastin AJ (1998b) Permeability of the blood-brain barrier to neurotrophins. Brain Res 788: 87-94
120. Pardridge WM (2002) Neurotrophins, neuroprotection and the blood brain barrier. Curr Opin Invest Drugs 3: 1753-1757
121. Parikh V, Evans DR, Khan MM, Mahadik SP (2003) Nerve growth factor in never-medicated first-episode psychotic and medicated chronic schizophrenic patients: possible implications for treatment outcome. Schizophr Res 60: 117-123
122. Pearse AG (1980) The common peptides and the cytochemistry of their cells of origin. Basic Appl Histochem 24: 63-73
123. Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW (1990) Widespread expression of BDNF but not NT3 by target areas of basal forebrain. Science 250: 290-294
124. Phillips HS, Hains JM, Laramee GR, Rosenthal A, Winslow JW (1991) BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease. Neuron 7: 695-702
125. Plotsky PM, Cunningham ET Jr, Widmaier EP (1989) Catecholaminergic modulation of corticotropin-releasing factor and adrenocorticotropin secretion. Endocr Rev 10: 437-458
126. Raedler TJ, Knable MB, Weinberger DR (1998) Schizophrenia as a developmental disorder of the cerebral cortex. Curr Opin Neurobiol 8: 157-161
127. Radka SF, Holst PA, Fritsche M, Altar CA (1996) Presence of brain-derived neurotrophic factor in brain and human and rat but not mouse serum detected by a sensitive and specific immunoassay. Brain Res 709: 122-301
128. Rajkowska G (2000) Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry 48: 766-777
129. Roßner S, Ueberham U, Schliebs R, Perez-Polo JR, Bigl V (1998) The regulation of amyloid precursor protein metabolism by cholinergic mechanisms and neurotrophin receptor signaling. Prog Neurobiol 56: 541-569
130. Russo-Neustadt A (2003) Brain-derived neurotrophic factor, behavior, and new directions for the treatment of mental disorders. Semin Clin Neuropsychiatry 8: 109-118
131. Russo-Neustadt A, Beard RC, Cotman CW (1999) Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology 21: 679-682
132. Russo-Neustadt AA, Beard RC, Huang YM, Cotman CW (2000) Physical activity and anti-depressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus. Neuroscience 101: 305-312
133. Russo-Neustadt A, Ha T, Ramirez R, Kesslak JP (2001) Physical activity-antidepressant treatment combination: impact on brain-derived neurotrophic factor and behavior in an animal model. Behav Brain Res 120: 87-95
134. Rylett RJ, Williams LR (1994) Role of neurotrophins in cholinergic-neuron function in the adult and aged CNS. Trends Neurosci 17: 486-490
135. Santarelli L, Saxe M, Gross C, Surget A, Bttaglia F, Dulawa S, Weistaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003) Requirement of hippocampal neurogenesis for the behavioural effects of antidepressants. Science 301: 805-809
136. Saragovi HU, Zaccaro MC (2002) Small molecule peptidomimetic ligands of neurotrophin receptors, identifying binding sites, activation sites and regulatory site. Curr Pharmaceut Design 8: 2201-2216
137. Scaccianoce S, Cigliana G, Nicolai R, Muscolo L, Porcu A, Narvarra D, Perez-Scaccianoce S, Lombarde K, Angelucci L (2000) Nerve growth factor brain concentration and stress: changes depend on type of stressor and age. Int J Dev Neurosci 18: 469-479
138. Schaub RT, Anders D, Golz G, Göhringer K, Hellweg R (2002) Serum nerve growth factor concentration and its role in the preclinical stage of dementia. Am J Psychiatry 159: 1227-1229
139. Schinder AF, Poo M (2000) The neurotrophin hypothesis for synaptic plasticity. Trends Neurosci 23: 639-645
140. Schotte A, Janssen PF, Megens AA, Leysen JE (1993) Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured ex vivo by quantitative autoradiography. Brain Res 63: 191-202
141. Schramm M, Falkai P, Feldmann N, Knable MB, Bayer TA (1998) Reduced tyrosine kinase receptor C mRNA levels in the frontal cortex of patients with schizophrenia. Neurosci Lett 257: 65-68
142. Scott SA, Mufson EJ, Weingartner JA, Skau KA, Crutcher KA (1995) Nerve growth factor in Alzheimer's disease: increased levels throughout the brain coupled with declines in nucleus basalis. J Neurosci 15: 6213-6221
143. Sendera TJ, Ma SY, Jaffar S, Kozlowski PB, Kordower JH, Mawal Y, Saragovi HU, Mufson EJ (2000) Reduction in TrkA immunoreactive neurons is not associated with an overexpression of galaninergic fibers within the nucleus basalis in Down's syndrome. J Neurochem 74: 1185-1196
144. Sheline YI (2000) 3D MRI studies of neuroanatomic changes in unipolar major depression: the role of stress and medical comorbidity. Biol Psych 48: 791-800
145. Shelton DL, Reichardt LF (1986) Studies on the expression of the nerve growth factor (NGF) gene in the central nervous system: level and regional distribution of NGF mRNA suggest that NGF functions as a trophic factor for several distinct populations of neurons. Proc Natl Acad Sci USA 83: 2714-2718
146. Sheridan JF, Stark JL, Avitsur R, Padgett DA (2000) Social disruption, immunity, and susceptibility to viral infection. Role of glucocorticoid insensitivity and NGF. Ann NY Acad Sci 917: 894-905
147. Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M (2003) Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 54: 70-75
148. Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS (2002) Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 22: 3251-3261
149. Siegel GJ, Chauhan NB (2000) Neurotrophic factors in Alzheimer's and Parkinson's disease brain. Brain Res Rev 33: 199-227
150. Singh M, Meyer EM, Simpkins JW (1995) The effect of ovariectomy and estradiol replacement on brain-derived neurotrophic factor messenger ribonucleic acid expression in cortical and hippocampal brain regions of female Sprague-Dawley rats. Endocrinology 136: 2320-2324
151. Siuciak JA, Lewis DR, Wiegand SJ, Lindsay RM (1997) Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacol Biochem Behav 56: 131-137
152. Smith MA (1996) Hippocampal vulnerability to stress and aging: possible role of neurotrophic factors. Behav Brain Res 78: 25-36
153. Smith MA, Makino S, Kvetnansky R, Post RM (1995) Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and NT-3 mRNA in the hippocampus. J Neurosci 15: 1768-1777
154. Soontornniyomkij V, Wang G, Pittman CA, Wiley CA, Achim CL (1998) Expression of brain-derived neurotrophic factor protein in activated microglia of human immunodeficiency virus type 1 encephalitis. Neuropathol Appl Neurobiol 24: 453-460
155. Sortino MA, Canonico PL (1997) Neurotrophic factors, neuroprotection and hypothalamic function. Aging (Milano) 9: 75-76
156. Taglialatela G, Angelucci L, Scaccianoce S, Foreman PJ, Perez-Polo JR (1991) Nerve growth factor modulates the activation of the hypothalamo- pituitary-adrenocortical axis during the stress response. Endocrinology 129: 2212-2218
157. Takahashi M, Shirakawa O, Toyooka K, Kitamura N, Hashimoto T, Maeda K, Koizumi S, Wakabayashi K, Takahashi H, Someya T, Nawa H (2000) Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients. Mol Psychiatry 5: 293-300
158. Tanaka Y, Ujike H, Fujiwara Y, Takeda T, Takehisa Y, Kodama M, Otsuki S, Kuroda S (1998) Schizophrenic psychoses and the CNTF null mutation. Neuroreport 9: 981-983
159. Terry AV Jr, Hill WD, Parikh V, Waller JL, Evans DR, Mahadik SP (2003) Differential effects of haloperidol, risperidone, and clozapine exposure on cholinergic markers and spatial learning performance in rats. Neuropsychopharmacology 28: 300-309
160. Thoenen H (1995) Neurotrophins and neuronal plasticity. Science 270: 593-598
161. Thoenen H (2001) Treatment of degenerative disorders of the nervous system: from helpless descriptive categorization to rational therapeutic approaches. In: Ingoglia NA, Murray N (eds) Axonal regeneration in the central nervous system. M Dekker, New York, pp 675-697
162. Thoenen H, Barde YA, Davies AM, Johnson JE (1987a) Neurotrophic factors and neuronal death. Ciba Found Symp 126: 82-95
163. Thoenen H, Bandtlow C, Heumann R (1987b) The physiological function of nerve growth factor in the central nervous system: comparison with the periphery. Rev Physiol Biochem Pharmacol 109: 145-178
164. Thome J, Durany N, Palomo A, Foley P, Harsányi A, Baumer A, Hashimoto E, Cruz-Sánchez FF, Riederer P (1997) Variants in neurotrophic factor genes (CNTF, NT3) and schizophrenic psychoses: no associations in a Spanish population. Psychiatry Res 71: 1-5
165. Thome J, Foley P, Riederer P (1998) Neurotrophic factors and the maldevelopmental hypothesis of schizophrenic psychoses. J Neural Transm 105: 85-100
166. Thome J, Sakai N, Shin KH, Steffen C, Zhang YJ, Impey S, Storm D, Duman RS (2000) cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. J Neurosci 20: 4030-4036
167. Toyooka K, Asama K, Watanabe Y, Muratake T, Takahashi M, Someya T, Nawa H (2002) Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients. Psychiatry Res 110: 249-257
168. Tuszynski MH, Sang H, Yoshida K, Gage FH (1991) Recombinant human nerve growth factor infusion prevents cholinergic neuronal degeneration in the adult primate brain. Ann Neurol 30: 625-636
169. Ueyama T, Kawai Y, Nemoto K, Sekimoto M, Tone S, Senba E (1997) Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain. Neurosci Res 28: 103-110
170. Vaidya VA, Marek GJ, Aghajanian GK, Duman RS (1997) 5-HT2A receptor-mediated regulation of brain-derived neurotrophic factor mRNA in the hippocampus and the neocortex. J Neurosci 17: 2785-2795
171. Vaidya VA, Siuciak JA, Duman RS (1999) Hippocampal mossy fiber sprouting induced by chronic electroconvulsive seizures. Neuroscience 89: 157-166
172. Van der Zee CEEM, Lourenssen S, Stanisz J, Diamond J (1995) NGF deprivation of adult rat brain results in cholinergic hypofunction and selective impairments in spatial learning. Eur J Neurosci 7: 160-168
173. Virgos C, Martorell L, Valero J, Figuera L, Civeira F, Joven J, Labad A, Vilella E (2001) Association study of schizophrenia with polymorphisms at six candidate genes. Schizophr Res 49: 65-71
174. von Richthofen S, Lang UE, Hellweg R (2003) Effects of different kinds of acute stress on nerve growth factor content in rat brain. Brain Res 987: 207-213
175. Wassink TH, Nelson JJ, Crowe RR, Andreasen NC (1999) Heritability of BDNF alleles and their effect on brain morphology in schizophrenia. Am J Med Genet 88: 724-728
176. Weickert CS, Hyde TM, Lipska BK, Herman MM, Weinberger DR, Kleinman JE (2003) Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia. Mol Psychiatry 8: 592-610
177. Weinberger DR (1999) Cell biology of the hippocampal formation in schizophrenia. Biol Psychiatry 45: 395-402
178. Winkler J, Thal LJ, Gage FH, Fisher LJ (1998) Cholinergic strategies for Alzheimer's disease. J Mol Med 76: 555-567
179. Yamada K, Mizuno M, Nabeshima T (2002) Role for brain-derived neurotrophic factor in learning and memory. Life Sci 70: 735-740
180. Yamamoto H, Gurney ME (1990) Human platelets contain brain-derived neurotrophic factor. J Neurosci 10: 3469-3478