CNS Drugs

, Volume 16, Issue 6, pp 361–372

Morphological Brain Changes in Depression

Can Antidepressants Reverse Them?
Current Opinion

Abstract

Structural neuroimaging and postmortem histopathological studies of the brain have revealed morphological changes in cortical and subcortical regions in individuals diagnosed with depression. Moreover, these regions are known to be functionally altered in mood disorders. This indicates that the morphological changes might be directly involved in the pathophysiology of depression, and implies that antidepressants may be able to regulate or reverse the detected structural abnormalities.

Work with animal models has shown that antidepressants are capable of inducing structural alterations in dendrites and axons and changes in the numbers of neural cells. However, there have been no studies in the human brain that have directly addressed whether antidepressant treatment can reverse or regulate the depression-related structural changes. Nevertheless, experience with lithium in bipolar disorder and antipsychotics in schizophrenia suggests that treatment with psychotropic drugs can result in structural changes that are consistent with reversion towards normal values.

Clearly, ascertaining the role of the reversal of structural changes in the therapeutic actions of antidepressants will require further longitudinal studies and careful comparisons between those patients with mood disorder who are treated with antidepressants and those who are not.

References

  1. 1.
    Charney DS. Monoamine dysfunction and the pathophysiology and treatment of depression. J Clin Psychiatry 1998; 59Suppl. 14: 11–4PubMedGoogle Scholar
  2. 2.
    Wong ML, Licinio J. Research and treatment approaches to depression. Nat Rev Neurosci 2001; 2(5): 343–51PubMedCrossRefGoogle Scholar
  3. 3.
    Siever LJ, Davis KL. Overview: toward a dysregulation hypothesis of depression. Am J Psychiatry 1985; 142(9): 1017–31PubMedGoogle Scholar
  4. 4.
    Drevets WC. Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Prog Brain Res 2000; 126: 413–31PubMedCrossRefGoogle Scholar
  5. 5.
    Drevets WC. Neuroimaging studies of mood disorders: implications for a neural model of major depression. Biol Psychiatry 2000; 48(8): 813–29PubMedCrossRefGoogle Scholar
  6. 6.
    Rajkowska G. Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry 2000; 48(8): 766–77PubMedCrossRefGoogle Scholar
  7. 7.
    Cotter DR, Pariante CM, Rajkowska G. Glial pathology and major psychiatric disorders. In: Agam G, Everall IP, Belmaker RH, editors. The postmortem brain in psychiatric research. Boston (MA): Kluwer Academic Publishers, 2002: 49–73Google Scholar
  8. 8.
    Manji HK, Drevets WC, Charney DS. The cellular neurobiology of depression. Nat Med 2001; 7(5): 541–7PubMedCrossRefGoogle Scholar
  9. 9.
    Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry 1997; 54: 597–606PubMedCrossRefGoogle Scholar
  10. 10.
    Duman RS, Malberg J, Thome J. Neural plasticity to stress and antidepressant treatment. Biol Psychiatry 1999; 46(9): 1181–91PubMedCrossRefGoogle Scholar
  11. 11.
    Manji HK, Moore GJ, Rajkowska G, et al. Neuroplasticity and cellular resilience in mood disorders. Mol Psychiatry 2000; 5(6): 578–93PubMedCrossRefGoogle Scholar
  12. 12.
    Swerdlow NR, Amalric M, Koob GF. Nucleus accumbens opiatedopamine interactions and locomotor activation in the rat: evidence for a pre-synaptic locus. Pharmacol Biochem Behav 1987; 26(4): 765–9PubMedCrossRefGoogle Scholar
  13. 13.
    Djuric VJ, Dunn E, Overstreet DH, et al. Antidepressant effect of ingested nicotine in female rats of Flinders resistant and sensitive lines. Physiol Behav 1999; 67(4): 533–7PubMedCrossRefGoogle Scholar
  14. 14.
    Nowak G, Ordway GA, Paul IA. Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims. Brain Res 1995; 675(1–2): 157–64PubMedCrossRefGoogle Scholar
  15. 15.
    Bouron A, Chatton JY. Acute application of the tricyclic anti-depressant desipramine presynaptically stimulates the exocytosis of glutamate in the hippocampus. Neuroscience 1999; 90(3): 729–36PubMedCrossRefGoogle Scholar
  16. 16.
    Videbech P. PET measurements of brain glucose metabolism and blood flow in major depressive disorder: a critical review. Acta Psychiatr Scand 2000; 101(1): 11–20PubMedCrossRefGoogle Scholar
  17. 17.
    Stoll AL, Renshaw PF, Yurgelun-Todd DA, et al. Neuroimaging in bipolar disorder: what have we learned? Biol Psychiatry 2000; 48(6): 505–17PubMedCrossRefGoogle Scholar
  18. 18.
    Strakowski SM, DelBello MP, Adler C, et al. Neuroimaging in bipolar disorder. Bipolar Disord 2000; 2 (3 Pt 1): 148–64PubMedCrossRefGoogle Scholar
  19. 19.
    George MS, Ketter TA, Post RM. SPECT and PET imaging in mood disorders. J Clin Psychiatry 1993; 54: 6–13PubMedGoogle Scholar
  20. 20.
    Ketter TA, George MS, Kimbrell TA, et al. Functional brain imaging, limbic function, and affective disorders. Neuroscientist 1996; 2: 55–65Google Scholar
  21. 21.
    Drevets WC, Kishore MG, Krishnan RKR. Neuroimaging studies of mood disorders. In: Charney DS, Nestler EJ, Bunney BS, editors. Neurobiology of mental illness. New York: Oxford University Press, 1999: 394–418Google Scholar
  22. 22.
    Soares J, Mann J. The anatomy of mood disorders — review of structural neuroimaging studies. Biol Psychiatry 1997;41(1): 86–106PubMedCrossRefGoogle Scholar
  23. 23.
    Sheline Y, Wang P, Gado M, et al. Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci U S A 1996; 93(9): 3908–13PubMedCrossRefGoogle Scholar
  24. 24.
    Sheline YI, Gado MH, Price JL. Amygdala core nuclei volumes are decreased in recurrent major depression. Neuroreport 1998; 9(9): 2023–8PubMedCrossRefGoogle Scholar
  25. 25.
    Sheline YI, Sanghavi M, Mintun MA, et al. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 1999; 19(12): 5034–43PubMedGoogle Scholar
  26. 26.
    Rajkowska G, Miguel-Hidalgo JJ, Wei J, et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 1999; 45(9): 1085–98PubMedCrossRefGoogle Scholar
  27. 27.
    Rajkowska G, Halaris A, Selemon L. Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol Psychiatry 2001; 49: 741–52PubMedCrossRefGoogle Scholar
  28. 28.
    Auer DP, Putz B, Kraft E, et al. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 2000; 47: 305–13PubMedCrossRefGoogle Scholar
  29. 29.
    Winsberg ME, Sachs N, Tate DL, et al. Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder. Biol Psychiatry 2000; 47: 475–81PubMedCrossRefGoogle Scholar
  30. 30.
    Miguel-Hidalgo JJ, Baucom C, Dilley G, et al. GFAP-immuno-reactivity in the prefrontal cortex distinguishes young from old adults in major depressive disorder. Biol Psychiatry 2000; 48: 860–72CrossRefGoogle Scholar
  31. 31.
    Miguel-Hidalgo JJ, Konick L, Overholser JC, et al. Glial pathology in dorsolateral prefrontal cortex (dlPFC) in alcohol dependence with and without depressive symptoms [abstract]. Soc Neurosci Abstr 2001; 27: 572.10Google Scholar
  32. 32.
    Öngür D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci U S A 1998; 95(22): 13290–5PubMedCrossRefGoogle Scholar
  33. 33.
    Cotter D, Mackay D, Landau S, et al. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry 2001; 58(6): 545–53PubMedCrossRefGoogle Scholar
  34. 34.
    Thase ME, Frank E, Kupfer DJ. Biological processes in major depression. In: Beckham EE, Leber WR, editors. Handbook of depression: treatment, assessment and research. Home-wood (IL): Dorsey, 1985: 816–913Google Scholar
  35. 35.
    Finley PR. Selective serotonin reuptake inhibitors: pharmacologic profiles and potential therapeutic distinctions. Ann Pharmacotherapy 1994; 28(12): 1359–69Google Scholar
  36. 36.
    Gorman JM, Sullivan G. Noradrenergic approaches to antide-pressant therapy. J Clin Psychiatry 2000; 61 Suppl. 1: 13–6Google Scholar
  37. 37.
    Owens MJ, Morgan WN, Plott SJ, et al. Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther 1997; 283(3): 1305–22PubMedGoogle Scholar
  38. 38.
    Moller HJ. Are all antidepressants the same? J Clin Psychiatry 2000; 61Suppl. 6: 24–8PubMedGoogle Scholar
  39. 39.
    Kramer MS, Cutler N, Feighner J, et al. Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 1998; 281(5383): 1640–5PubMedCrossRefGoogle Scholar
  40. 40.
    Norrholm SD, Ouimet CC. Chronic fluoxetine administration to juvenile rats prevents age-associated dendritic spine proliferation in hippocampus. Brain Res 2000; 883(2): 205–15PubMedCrossRefGoogle Scholar
  41. 41.
    Norrholm SD, Ouimet CC. Altered dendritic spine density in animal models of depression and in response to antidepressant treatment. Synapse 2001; 42(3): 151–63PubMedCrossRefGoogle Scholar
  42. 42.
    Benes FM, Vincent SL. Changes in dendritic spine morphology in response to increased availability of monoamines in rat medial prefrontal cortex. Synapse 1991; 9(3): 235–7PubMedCrossRefGoogle Scholar
  43. 43.
    Wilde MI, Benfield P. Tianeptine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depression and coexisting anxiety and depression. Drugs 1995; 49(3): 411–39Google Scholar
  44. 44.
    Magarinos AM, Deslandes A, McEwen BS. Effects of antidepressants and benzodiazepine treatments on the dendritic structure of CA3 pyramidal neurons after chronic stress. Eur J Pharmacol 1999; 371(2–3): 113–22PubMedCrossRefGoogle Scholar
  45. 45.
    McEwen BS, Conrad CD, Kuroda Y, et al. Prevention of stress-induced morphological and cognitive consequences. Eur Neuropsychopharmacol 1997; 7Suppl. 3: S323–8PubMedCrossRefGoogle Scholar
  46. 46.
    Czeh B, Michaelis T, Watanabe T, et al. Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci U S A 2001; 98(22): 12796–801PubMedCrossRefGoogle Scholar
  47. 47.
    Kuroda Y, McEwen BS. Effect of chronic restraint stress and tianeptine on growth factors, growth-associated protein-43 and microtubule-associated protein 2 mRNA expression in the rat hippocampus. Brain Res Mol Brain Res 1998; 59(1): 35–9PubMedCrossRefGoogle Scholar
  48. 48.
    Duman RS, Malberg J, Nakagawa S, et al. Neuronal plasticity and survival in mood disorders. Biol Psychiatry 2000; 48(8): 732–9PubMedCrossRefGoogle Scholar
  49. 49.
    Shankaranarayana Rao BS, Lakshmana MK, Meti BL, et al. Chronic (−) deprenyl administration alters dendritic morphology of layer III pyramidal neurons in the prefrontal cortex of adult Bonnett monkeys. Brain Res 1999; 821(1): 218–23PubMedCrossRefGoogle Scholar
  50. 50.
    Lakshmana MK, Rao BS, Dhingra NK, et al. Chronic (−) deprenyl administration increases dendritic arborization in CA3 neurons of hippocampus and AChE activity in specific regions of the primate brain. Brain Res 1998; 796(1–2): 38–44PubMedCrossRefGoogle Scholar
  51. 51.
    Tatton WG, Wadia JS, Ju WY, et al. (−)-Deprenyl reduces neuronal apoptosis and facilitates neuronal outgrowth by altering protein synthesis without inhibiting monoamine oxidase. J Neural Transm Suppl 1996; 48: 45–59PubMedGoogle Scholar
  52. 52.
    Koutsilieri E, O’Callaghan JF, Chen TS, et al. Selegiline enhances survival and neurite outgrowth of MPP (+)-treated dopaminergic neurons. Eur J Pharmacol 1994; 269(3): R3–4PubMedCrossRefGoogle Scholar
  53. 53.
    Wong KL, Chuang TY, Bruch RC, et al. Amitriptyline inhibits neurite outgrowth in chick cerebral neurons: a possible mechanism. J Neurobiol 1993; 24(4): 474–87PubMedCrossRefGoogle Scholar
  54. 54.
    Smialowska M, Bal Klara A, Smialowski A. Chronic imipramine diminishes the nuclear size of neurons in the locus coeruleus and cingular cortex but not in the hippocampus of the rat brain. Neuroscience 1988; 26(3): 803–7PubMedCrossRefGoogle Scholar
  55. 55.
    Kitayama I, Yaga T, Kayahara T, et al. Long-term stress degenerates, but imipramine regenerates, noradrenergic axons in the rat cerebral cortex. Biol Psychiatry 1997; 42(8): 687–96PubMedCrossRefGoogle Scholar
  56. 56.
    Nakamura S. Antidepressants induce regeneration of catechol-aminergic axon terminals in the rat cerebral cortex. Neurosci Letters 1990; 111(1–2): 64–8CrossRefGoogle Scholar
  57. 57.
    Nakamura S. Axonal sprouting of noradrenergic locus coeruleus neurons following repeated stress and antidepressant treatment. Prog Brain Res 1991; 88: 587–98PubMedCrossRefGoogle Scholar
  58. 58.
    Bastos EF, Marcelino JL, Amaral AR, et al. Fluoxetine-induced plasticity in the rodent visual system. Brain Res 1999; 824(1): 28–35PubMedCrossRefGoogle Scholar
  59. 59.
    Bal-Klara A, Bird MM. The effects of various antidepressant drugs on the fine-structure of neurons of the cingulate cortex in culture. Neuroscience 1990; 37(3): 685–92PubMedCrossRefGoogle Scholar
  60. 60.
    Naudon L, Leroux-Nicollet I, El Yacoubi M, et al. The density of Nissl stained cells and the size of some cerebral regions are decreased in a genetic animal model of depression [abstract]. Soc Neurosci Abstr 2001; 27: 974Google Scholar
  61. 61.
    Rosoklija G, Toomayan G, Ellis SP, et al. Structural abnormalities of subicular dendrites in subjects with schizophrenia and mood disorders: preliminary findings. Arch Gen Psychiatry 2000; 57(4): 349–56PubMedCrossRefGoogle Scholar
  62. 62.
    Jorgensen OS, Riederer P. Increased synaptic markers in hippocampus of depressed patients. J Neural Transm 1985; 64(1): 55–66PubMedCrossRefGoogle Scholar
  63. 63.
    Vawter MP, Freed WJ, Kleinman JE. Neuropathology of bipolar disorder. Biol Psychiatry 2000; 48(6): 486–504PubMedCrossRefGoogle Scholar
  64. 64.
    Mayberg HS. Depression. In: Mazziotta JC, Toga AW, Frackowiak RSJ, editors. Brain mapping: the disorders. San Diego (CA): Academic Press, 2000: 485–507CrossRefGoogle Scholar
  65. 65.
    Mayberg HS, Brannan SK, Tekell JL, et al. Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 2000; 48(8): 830–43PubMedCrossRefGoogle Scholar
  66. 66.
    Brody AL, Saxena S, Silverman DH, et al. Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine. Psychiatry Res 1999; 91(3): 127–39PubMedCrossRefGoogle Scholar
  67. 67.
    Brody AL, Saxena S, Stoessel P, et al. Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings. Arch Gen Psychiatry 2001; 58(7): 631–40PubMedCrossRefGoogle Scholar
  68. 68.
    Brody AL, Saxena S, Mandelkern MA, et al. Brain metabolic changes associated with symptom factor improvement in major depressive disorder. Biol Psychiatry 2001; 50(3): 171–8PubMedCrossRefGoogle Scholar
  69. 69.
    Ogura A, Morinobu S, Kawakatsu S, et al. Changes in regional brain activity in major depression after successful treatment with antidepressant drugs. Acta Psychiatr Scand 1998; 98(1): 54–9PubMedCrossRefGoogle Scholar
  70. 70.
    Young RC, Kalayam B, Nambudiri DE, et al. Brain morphology and response to nortriptyline in geriatric depression. Am J Geriatr Psychiatry 1999; 7(2): 147–50PubMedGoogle Scholar
  71. 71.
    Vakili K, Pillay SS, Lafer B, et al. Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biol Psychiatry 2000; 47(12): 1087–90PubMedCrossRefGoogle Scholar
  72. 72.
    Mervaala E, Fohr J, Kononen M, et al. Quantitative MRI of the hippocampus and amygdala in severe depression. Psychol Med 2000; 30(1): 117–25PubMedCrossRefGoogle Scholar
  73. 73.
    Moore GJ, Bebchuk JM, Wilds IB, et al. Lithium-induced increase in human brain grey matter. Lancet 2000; 356(9237): 1241–2PubMedCrossRefGoogle Scholar
  74. 74.
    Moore GJ, Rajarethinam RP, Cortese BM, et al. Regionally specific increases in human brain gray matter with chronic lithium treatment [abstract]. Soc Neurosci Abstr 2001; 27: 111.8Google Scholar
  75. 75.
    Drevets W, Price J, Simpson JR J, et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997; 386(6627): 824–7PubMedCrossRefGoogle Scholar
  76. 76.
    Moore GJ, Bebchuk JM, Hasanat K, et al. Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2′s neurotrophic effects? Biol Psychiatry 2000; 48(1): 1–8PubMedCrossRefGoogle Scholar
  77. 77.
    Sharma R, Venkatasubramanian PN, Barany M, et al. Proton magnetic resonance spectroscopy of the brain in schizophrenic and affective patients. Schizophr Res 1992; 8(1): 43–9Google Scholar
  78. 78.
    Henn FA, Braus DF. Structural neuroimaging in schizophrenia. An integrative view of neuromorphology. Eur Arch Psychiatry Clin Neurosci 1999; 249Suppl. 4: 48–56PubMedCrossRefGoogle Scholar
  79. 79.
    Scheepers FE, Gispen-de Wied CC, Hulshoff Pol HE, et al. Effect of clozapine on caudate nucleus volume in relation to symptoms of schizophrenia. Am J Psychiatry 2001; 158(4): 644–6PubMedCrossRefGoogle Scholar
  80. 80.
    Frazier JA, Giedd JN, Kaysen D, et al. Childhood-onset schizophrenia: brain MRI rescan after 2 years of clozapine maintenance treatment. Am J Psychiatry 1996; 153(4): 564–6PubMedGoogle Scholar
  81. 81.
    Scheepers FE, de Wied CC, Hulshoff Pol HE, et al. The effect of clozapine on caudate nucleus volume in schizophrenic patients previously treated with typical antipsychotics. Neuro-psychopharmacology 2001; 24(1): 47–54CrossRefGoogle Scholar
  82. 82.
    Lee H, Tarazi FI, Chakos M, et al. Effects of chronic treatment with typical and atypical antipsychotic drugs on the rat striatum. Life Sci 1999; 64(18): 1595–602PubMedCrossRefGoogle Scholar
  83. 83.
    Chakos MH, Lieberman JA, Bilder RM, et al. Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. Am J Psychiatry 1994; 151(10): 1430–6PubMedGoogle Scholar
  84. 84.
    Keshavan MS, Rosenberg D, Sweeney JA, et al. Decreased caudate volume in neuroleptic-naive psychotic patients. Am J Psychiatry 1998; 155(6): 774–8PubMedGoogle Scholar
  85. 85.
    Shihabuddin L, Buchsbaum MS, Hazlett EA, et al. Dorsal striatal size, shape, and metabolic rate in never-medicated and previously medicated schizophrenics performing a verbal learning task. Arch Gen Psychiatry 1998; 55(3): 235–43PubMedCrossRefGoogle Scholar
  86. 86.
    Selemon LD, Lidow MS, Goldman-Rakic PS. Increased volume and glial density in primate prefrontal cortex associated with chronic antipsychotic drug exposure. Biol Psychiatry 1999; 46(2): 161–72PubMedCrossRefGoogle Scholar
  87. 87.
    Starkman MN, Giordani B, Gebarski SS, et al. Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing’s disease. Biol Psychiatry 1999; 46(12): 1595–602PubMedCrossRefGoogle Scholar
  88. 88.
    Kelly WF, Kelly MJ, Faragher B. A prospective study of psychiatric and psychological aspects of Cushing’s syndrome. Clin Endocrinol (Oxf) 1996; 45(6): 715–20CrossRefGoogle Scholar
  89. 89.
    Zeiger MA, Fraker DL, Pass HI, et al. Effective reversibility of the signs and symptoms of hypercortisolism by bilateral ad-renalectomy. Surgery 1993; 114(6): 1138–43PubMedGoogle Scholar
  90. 90.
    Starkman MN, Schteingart DE, Schork MA. Cushing’s syndrome after treatment: changes in cortisol and ACTH levels, and amelioration of the depressive syndrome. Psychiatry Res 1986; 19(3): 177–88PubMedCrossRefGoogle Scholar
  91. 91.
    Starkman MN, Gebarski SS, Berent S, et al. Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing’s syndrome. Biol Psychiatry 1992; 32(9): 756–65PubMedCrossRefGoogle Scholar
  92. 92.
    Siuciak JA, Lewis DR, Wiegand SJ, et al. Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). Pharmacol Biochem Behav 1997; 56(1): 131–7PubMedCrossRefGoogle Scholar
  93. 93.
    Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 1995; 15(11): 7539–47PubMedGoogle Scholar
  94. 94.
    Nibuya M, Nestler EJ, Duman RS. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 1996; 16(7): 2365–72PubMedGoogle Scholar
  95. 95.
    Malberg JE, Eisch AJ, Nestler EJ, et al. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20(24): 9104–10PubMedGoogle Scholar
  96. 96.
    Malberg JE, Shirayama YS, Duman RS. The effect of antidepressant treatment and learned helplessness training on hippocampal neurogenesis in the adult rat [abstract]. Soc Neurosci Abstr 2001; 27: 974.6Google Scholar
  97. 97.
    Shimada A, Mason CA, Morrison ME. TrkB signaling modulates spine density and morphology independent of dendrite structure in cultured neonatal Purkinje cells. J Neurosci 1998; 18(21): 8559–70PubMedGoogle Scholar
  98. 98.
    Horch HW, Kruttgen A, Portbury SD, et al. Destabilization of cortical dendrites and spines by BDNF. Neuron 1999; 23(2): 353–64PubMedCrossRefGoogle Scholar
  99. 99.
    McAllister AK, Katz LC, Lo DC. Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic growth. Neuron 1997; 18(5): 767–78PubMedCrossRefGoogle Scholar
  100. 100.
    Kishino A, Ishige Y, Tatsuno T, et al. BDNF prevents and reverses adult rat motor neuron degeneration and induces axonal outgrowth. Exp Neurol 1997; 144(2): 273–86PubMedCrossRefGoogle Scholar
  101. 101.
    Lom B, Cohen-Cory S. Brain-derived neurotrophic factor differentially regulates retinal ganglion cell dendritic and axonal arborization in vivo. J Neurosci 1999; 19(22): 9928–38PubMedGoogle Scholar
  102. 102.
    Mamounas LA, Blue ME, Siuciak JA, et al. Brain-derived neurotrophic factor promotes the survival and sprouting of sero-tonergic axons in rat brain. J Neurosci 1995; 15(12): 7929–39PubMedGoogle Scholar
  103. 103.
    Kempermann G, Kuhn HG, Gage FH. Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc Natl Acad Sci U S A 1997; 94(19): 10409–14PubMedCrossRefGoogle Scholar
  104. 104.
    Markakis EA, Gage FH. Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles. J Comp Neurol 1999; 406(4): 449–60PubMedCrossRefGoogle Scholar
  105. 105.
    Kato T, Yokouchi K, Fukushima N, et al. Continual replacement of newly-generated olfactory neurons in adult rats. Neurosci Lett 2001; 307(1): 17–20PubMedCrossRefGoogle Scholar
  106. 106.
    Corotto FS, Henegar JA, Maruniak JA. Neurogenesis persists in the subependymal layer of the adult mouse brain. Neurosci Lett 1993; 149(2): 111–4PubMedCrossRefGoogle Scholar
  107. 107.
    Kornack DR, Rakic P. The generation, migration, and differentiation of olfactory neurons in the adult primate brain. Proc Natl Acad Sci U S A 2001; 98(8): 4752–7PubMedCrossRefGoogle Scholar
  108. 108.
    Kornack DR, Rakic P. Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci U S A 1999; 96(10): 5768–73PubMedCrossRefGoogle Scholar
  109. 109.
    Gould E, Reeves AJ, Fallah M, et al. Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci U S A 1999; 96(9): 5263–7PubMedCrossRefGoogle Scholar
  110. 110.
    Fuchs E, Flugge G. Stress, glucocorticoids and structural plasticity of the hippocampus. Neurosci Biobehav Rev 1998; 23(2): 295–300PubMedCrossRefGoogle Scholar
  111. 111.
    Cameron HA, Gould E. Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience 1994; 61(2): 203–9PubMedCrossRefGoogle Scholar
  112. 112.
    Duman RS, Nakagawa S, Malberg J. Regulation of adult neurogenesis by antidepressant treatment. Neuropsychopharmacology 2001; 25(6): 836–44PubMedCrossRefGoogle Scholar
  113. 113.
    Gould E, Reeves AJ, Graziano MS, et al. Neurogenesis in the neocortex of adult primates. Science 1999; 286(5439): 548–52PubMedCrossRefGoogle Scholar
  114. 114.
    Kornack DR, Rakic P. Cell proliferation without neurogenesis in adult primate neocortex. Science 2001; 294(5549): 2127–30PubMedCrossRefGoogle Scholar
  115. 115.
    Rakic P. Specification of cerebral cortical areas. Science 1988; 241: 170–6PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • José Javier Miguel-Hidalgo
    • 1
  • Grazyna Rajkowska
    • 1
  1. 1.Department of Psychiatry and Human BehaviorUniversity of Mississippi Medical CenterJacksonUSA

Personalised recommendations