Deafferentation enhances neurogenesis in the young and middle aged hippocampus but not in the aged hippocampus

Hippocampus

Volumn 21, Issue 6, 2011, Pages 631-646

  Shetty, Ashok K ^a,b   Hattiangady, Bharathi ^a,b   Rao, Muddanna S ^a,b   Shuai, Bing ^a,b  

^a DURHAM VA MEDICAL CENTER   (United States)

^b DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

5' bromodeoxyuridine; Adult neurogenesis; Aging; Dentate neurogenesis; DG; Doublecortin; Kainic acid; Neural stem cells; Rat; Stem cell differentiation; Stem cell proliferation

Indexed keywords

BROXURIDINE; KAINIC ACID;

AGE DISTRIBUTION; ANIMAL CELL; ARTICLE; BRAIN CORTEX; CONTROLLED STUDY; DEAFFERENTATION; DENTATE GYRUS; GRANULE CELL; HIPPOCAMPUS; HUMAN; HUMAN TISSUE; MALE; NERVE CELL DIFFERENTIATION; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NEURAL STEM CELL; NONHUMAN; PRIORITY JOURNAL; PYRAMIDAL NERVE CELL; RAT;

AGE FACTORS; AGING; ANIMALS; BROMODEOXYURIDINE; CELL COUNT; CELL DIFFERENTIATION; CELL PROLIFERATION; DENTATE GYRUS; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; KAINIC ACID; MALE; MICROTUBULE-ASSOCIATED PROTEINS; MODELS, ANIMAL; NEURAL STEM CELLS; NEUROGENESIS; NEURONS; NEUROPEPTIDES; RATS; RATS, INBRED F344;

EID: 79956362857     PISSN: 10509631     EISSN: 10981063     Source Type: Journal    
DOI: 10.1002/hipo.20776     Document Type: Article

References (108)

1. Aimone JB, Wiles J, Gage FH. 2006. Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci 9: 723-727.
2. Aizawa K, Ageyama N, Terao K, Hisatsune T. 2009. Primate-specific alterations in neural stem/progenitor cells in the aged hippocampus. Neurobiol Aging. Feb 5 [Epub].
3. Anderton BH, Callahan L, Coleman P, Davies P, Flood D, Jicha GA, Ohm T, Weaver C. 1998. Dendritic changes in Alzheimer's disease and factors that may underlie these changes. Prog Neurobiol 55: 595-609.
4. Bachstetter AD, Pabon MM, Cole MJ, Hudson CE, Sanberg PR, Willing AE Bickford PC, Gemma C. 2008. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain. BMC Neurosci 9: 22.
5. Bengzon J, Kokaia Z, Elmer E, Nanobashvili A, Kokaia M, Lindvall O. 1997. Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures. Proc Natl Acad Sci USA 94: 10432-10437.
6. Bizon JL, Gallagher M. 2003. Production of new cells in the rat dentate gyrus over the lifespan: Relation to cognitive decline. Eur J Neurosci 18: 215-219.
7. Bizon JL, Lee HJ, Gallagher M. 2004. Neurogenesis in a rat model of age-related cognitive decline. Aging Cell 3: 227-234.
8. Brazel CY, Limke TL, Osborne JK, Miura T, Cai J, Pevny L, Rao MS. 2005. Sox2 expression defines a heterogeneous population of neurosphere-forming cells in the adult murine brain. Aging Cell 4: 197-207.
9. Bruel-Jungerman E, Laroche S, Rampon C. 2005. New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment. Eur J Neurosci 21: 513-521.
10. Bruns JJr, Hauser WA. 2003. The epidemiology of traumatic brain injury: A review. Epilepsia 44( Suppl 10): 2-10.
11. Buckwalter MS, Yamane M, Coleman BS, Ormerod BK, Chin JT, Palmer T, Wyss-Coray T. 2006. Chronically increased transforming growth factor-beta1 strongly inhibits hippocampal neurogenesis in aged mice. Am J Pathol 169: 154-164.
12. Cameron HA, McKay RD. 1999. Restoring production of hippocampal neurons in old age. Nat Neurosci 2: 894-897.
13. Cameron HA, Woolley CS, McEwen BS, Gould E. 1993. Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neurosci 56: 337-344.
14. Cheng Q, Di Liberto V, Caniglia G, Mudò G. 2008. Time-course of GDNFand its receptor expression after brain injury in the rat. Neurosci Lett 439: 24-29.
15. Cotman CW, Scheff SW. 1979. Compensatory synapse growth in aged animals after neuronal death. Mech Ageing Dev 9: 103-117.
16. Crutcher KA. 2002. Aging and neuronal plasticity: Lessons from a model. Auton Neurosci 96: 25-32.
17. Darsalia V, Heldmann U, Lindvall O, Kokaia Z. 2005. Stroke-induced neurogenesis in aged brain. Stroke 36: 1790-1795.
18. Drapeau E, Abrous ND. 2008. Stem cell review series: Role of neurogenesis in age-related memory disorders. Aging Cell 7: 569-589.
19. Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza PV, Abrous DN. 2003. Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proc Natl Acad Sci USA 100: 14385-14390.
20. Drapeau E, Montaron MF, Aguerre S, Abrous DN. 2007. Learning-induced survival of new neurons depends on the cognitive status of aged rats. J Neurosci 27: 6037-6044.
21. Driscoll I, Hong NS, Craig LA, Sutherland LA, McDonald RJ. 2008. Enhanced cell death and learning deficits after a mini-stroke in aged hippocampus. Neurobiol Aging 29: 1847-1858.
22. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH. 1998. Neurogenesis in the adult human hippocampus. Nat Med 4: 1313-1317.
23. Ferrell RB, Tanev KS. 2002. Traumatic brain injury in older adults. Curr Psychiatry Rep 4: 354-362.
24. Fontana X, Nacher J, Soriano E, del Rio JA. 2006. Cell proliferation in the adult hippocampal formation of rodents and its modulation by entorhinal and fimbria-fornix afferents. Cereb Cortex 16: 301-312.
25. Forster E, Naumann T, Deller T, Straube A, Nitsch R, Frotscher M. 1997. Cholinergic sprouting in the rat fascia dentata after entorhinal lesion is not linked to early changes in neurotrophin messenger RNA expression. Neuroscience 80: 731-739.
26. Gemma C, Bachstetter AD, Cole MJ, Fister M, Hudson C, Bickford PC. 2007. Blockade of caspase-1 increases neurogenesis in the aged hippocampus. Eur J Neurosci 26: 2795-2803.
27. Gong C, Wang TW, Huang HS, Parent JM. 2007. Reelin regulates neuronal progenitor migration in intact and epileptic hippocampus. J Neurosci 27: 1803-1811.
28. Gould E, McEwen BS, Tanapat P, Galea LA, Fuchs E. 1997. Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 17: 2492-2498.
29. Gould E, Reeves AJ, Fallah M, Tanapat P, Gross CG, Fuchs E. 1999a. Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci USA 96: 5263-5267.
30. Gould E, Tanapat P, Hastings NB, Shors TJ. 1999b. Neurogenesis in adulthood: A possible role in learning. Trends Cogn Sci 3: 186-192.
31. Gray WP, Sundstrom LE. 1998. Kainic acid increases the proliferation of granule cell progenitors in the dentate gyrus of the adult rat. Brain Res 790: 52-59.
32. Hagihara H, Hara M, Tsunekawa K, Nakagawa Y, Sawada M, Nakano K. 2005. Tonic-clonic seizures induce division of neuronal progenitor cells with concomitant changes in expression of neurotrophic factors in the brain of pilocarpine-treated mice. Brain Res 39: 258-266.
33. Hattiangady B, Shetty AK. 2004. Subcutaneous administration of fibroblast growth factor-2 (FGF-2) enhances dentate neurogenesis in the injured aged hippocampus. Soc Neurosci (Abstr 31.12).
34. Hattiangady B, Shetty AK. 2007. Subcutaneous administration of BDNF dramatically enhances dentate neurogenesis in the injured aged hippocampus. Soc Neurosci (Abstr 562.12).
35. Hattiangady B, Shetty AK. 2008. Aging does not alter the number or phenotype of putative stem/progenitor cells in the neurogenic region of the hippocampus. Neurobiol Aging 29: 129-147.
36. Hattiangady B, Rao MS, Shetty AK. 2004. Chronic temporal lobe epilepsy is associated with severely declined dentate neurogenesis in the adult hippocampus. Neurobiol Dis 17: 473-490.
37. Hattiangady B, Rao MS, Shetty AK. 2008. Plasticity of hippocampal stem/progenitor cells to enhance neurogenesis in response to kainate-induced injury is lost by middle age. Aging Cell 7: 207-224.
38. Ihrie RA, Alvarez-Buylla A. 2008. Cells in the astroglial lineage are neural stem cells. Cell Tissue Res 331: 179-191.
39. Imayoshi I, Sakamoto M, Ohtsuka T, Takao K, Miyakawa T, Yamaguchi M, Mori K, Ikeda T, Itohara S, Kageyama R. 2008. Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat Neurosci 11: 1153-1161.
40. Jessberger S, Gage FH. 2008. Stem-cell-associated structural and functional plasticity in the aging hippocampus. Psychol Aging 23: 684-691.
41. Jessberger S, Zhao C, Toni N, Clemenson GDJr, Li Y, Gage FH. 2007. Seizure-associated, aberrant neurogenesis in adult rats characterized with retrovirus-mediated cell labeling. J Neurosci 27: 9400-9407.
42. Jessberger S, Clark RE, Broadbent NJ, Clemenson GDJr, Consiglio A, Lie DC, Squire LR, Gage FH. 2009. Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. Learn Mem 16: 147-154.
43. Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP, Greenberg DA. 2001. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci USA 98: 4710-4715.
44. Jin K, Sun Y, Xie L, Batteur S, Mao XO, Smelick C, Logvinova A and Greenberg DA. 2003. Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell 2: 175-183.
45. Jin K, Minami M, Xie L, Sun Y, Mao XO, Wang Y, Simon RP, Greenberg DA. 2004. Ischemia-induced neurogenesis is preserved but reduced in the aged rodent brain. Aging Cell 3: 373-377.
46. Kee N, Teixeira CM, Wang AH, Frankland PW. 2007. Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat Neurosci 10: 355-362.
47. Kempermann G, Gast D, Gage FH. 2002. Neuroplasticity in old age: Sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Ann Neurol 52: 135-143.
48. Kempermann G, Gast D, Kronenberg G, Yamaguchi M, Gage FH. 2003. Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development 130: 391-399.
49. Kempermann G, Jessberger S, Steiner B, Kronenberg G. 2004. Milestones of neuronal development in the adult hippocampus. Trends Neurosci 27: 447-452.
50. Kleindienst A, McGinn MJ, Harvey HB, Colello RJ, Hamm RJ, Bullock MR. 2005. Enhanced hippocampal neurogenesis by intraventricular S100B infusion is associated with improved cognitive recovery after traumatic brain injury. J Neurotrauma 22: 645-655.
51. Kornack DR, Rakic P. 1999. Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci USA 96: 5768-5773.
52. Kuhn HG, Dickinson-Anson H, Gage FH. 1996. Neurogenesis in the dentate gyrus of the adult rat: Age-related decrease of neuronal progenitor proliferation. J Neurosci 16: 2027-2033.
53. Leuner B, Gould E, Shors TJ. 2006. Is there a link between adult neurogenesis and learning? Hippocampus 16: 216-224.
54. Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Sonntag WE, Riddle DR. 2001. Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 107: 603-613.
55. Liu J, Solway K, Messing RO, Sharp FR. 1998. Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci 18: 7768-7778.
56. Lowenstein DH, Seren MS, Longo FM. 1993. Prolonged increases in neurotrophic activity associated with kainate-induced hippocampal synaptic reorganization. Neuroscience 56: 597-604.
57. Mattiesen WR, Tauber SC, Gerber J, Bunkowski S, Bruck W, Nau R. 2009. Increased neurogenesis after hypoxic-ischemic encephalopathy in humans is age-related. Acta Neuropathol 117: 525-535.
58. Monje ML, Toda H, Palmer TD. 2003. Inflammatory blockade restores adult hippocampal neurogenesis. Science 302: 1760-1765.
59. Nadler JV, Perry BW, Gentry C, Cotman CW. 1980a. Degeneration of hippocampal CA3 pyramidal cells induced by intraventricular kainic acid. J Comp Neurol 192: 333-359.
60. Nadler JV, Perry BW, Gentry C, Cotman CW. 1980b. Loss and reacquisition of hippocampal synapses after selective destruction of CA3-CA4 afferents with kainic acid. Brain Res 191: 387-403.
61. Nagahara AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM, Wang L, Blesch A, Kim A, Conner JM, Rockenstein E, Chao MV, Koo EH, Geschwind D, Masliah E, Chiba AA, Tuszynski MH. 2009. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nat Med 15: 331-337.
62. Nakagawa E, Aimi Y, Yasuhara O, Tooyama I, Shimada M, McGeer PL, Kimura H. 2000. Enhancement of progenitor cell division in the dentate gyrus triggered by initial limbic seizures in rat models of epilepsy. Epilepsia 41: 10-18.
63. Naumann T, Deller T, Bender R, Frotscher M. 1997. 192 IgG-saporin-induced loss of cholinergic neurons in the septum abolishes cholinergic sprouting after unilateral entorhinal lesion in the rat. Eur J Neurosci 9: 1304-1313.
64. Needels DL, Nieto-Sampedro M, Cotman CW. 1986. Induction of a neurite-promoting factor in rat brain following injury or deafferentation. Neuroscience 18: 517-526.
65. Olariu A, Cleaver KM, Cameron HA. 2007. Decreased neurogenesis in aged rats results from loss of granule cell precursors without lengthening of the cell cycle. J Comp Neurol 501: 659-667.
66. Parent JM. 2003. Injury-induced neurogenesis in the adult mammalian brain. Neuroscientist 9: 261-272.
67. Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH. 1997. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci 17: 3727-3738.
68. Rai K, Hattiangady B, Shetty AK. 2007. Enhanced production and dendritic growth of new dentate granule cells in the middle-aged and aged hippocampus following intracerebroventricular FGF-2 infusions. Eur J Neurosci 26: 1765-1779.
69. Ramirez JJ. 2001. The role of axonal sprouting in functional reorganization after CNS injury: Lessons from the hippocampal formation. Restor Neurol Neurosci 19: 237-262.
70. Ransmayr G, Cervera P, Hirsch E, Ruberg M, Hersh LB, Duyckaerts C, Hauw JJ, Delumeau C, Agid Y. 1989. Choline acetyltransferase-like immunoreactivity in the hippocampal formation of control subjects and patients with Alzheimer's disease. Neuroscience 32: 701-714.
71. Rao MS, Shetty AK. 2004. Efficacy of doublecortin as a marker to analyse the absolute number and dendritic growth of newly generated neurons in the adult dentate gyrus. Eur J Neurosci 19: 234-246.
72. Rao MS, Hattiangady B, Abdel-Rahman A, Stanley DP, Shetty AK. 2005. Newly born cells in the ageing dentate gyrus display normal migration, survival and neuronal fate choice but endure retarded early maturation. Eur J Neurosci 21: 464-476.
73. Rao MS, Hattiangady B, Shetty AK. 2006a. The window and mechanisms of major age-related decline in the production of new neurons within the dentate gyrus of the hippocampus. Aging Cell 5: 545-558.
74. Rao MS, Hattiangady B, Shetty AK. 2006b. Fetal hippocampal CA3 cell grafts enriched with FGF-2 and BDNF exhibit robust long-term survival and integration and suppress aberrant mossy fiber sprouting in the injured middle-aged hippocampus. Neurobiol Dis 21: 276-290.
75. Rao MS, Hattiangady B, Shetty AK. 2008. Status epilepticus during old age is not associated with enhanced hippocampal neurogenesis. Hippocampus 18: 931-944.
76. Rossner S. 1997. Cholinergic immunolesions by 192IgG-saporin-Useful tool to simulate pathogenic aspects of Alzheimer's disease. Int J Dev Neurosci 15: 835-850.
77. Sairanen M, Lucas G, Ernfors P, Castren M, Castren E. 2005. Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci 25: 1089-1094.
78. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R. 2003. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301: 805-809.
79. Scharfman HE, Gray WP. 2007. Relevance of seizure-induced neurogenesis in animal models of epilepsy to the etiology of temporal lobe epilepsy. Epilepsia 48( Suppl 2): 33-41.
80. Schauwecker PE, Cheng HW, Serquinia RM, Mori N, McNeill TH. 1995. Lesion-induced sprouting of commissural/associational axons and induction of GAP-43 mRNA in hilar and CA3 pyramidal neurons in the hippocampus are diminished in aged rats. J Neurosci 15: 2462-2470.
81. Scheff S. 2003. Reactive synaptogenesis in aging and Alzheimer's disease: Lessons learned in the Cotman laboratory. Neurochem Res 28: 1625-1630.
82. Seri B, Garcia-Verdugo JM, McEwen BS, Alvarez-Buylla A. 2001. Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21: 7153-7160.
83. Shay JW, Wright WE. 2000. Hayflick, his limit, and cellular ageing. Nat Rev Mol Cell Biol 1: 72-76.
84. Shetty AK, Hattiangady B. 2007. Prospects of stem cell therapy for temporal lobe epilepsy. Stem Cells 25: 2396-2407.
85. Shetty AK, Turner DA. 1999a. Aging impairs axonal sprouting response of dentate granule cells following target loss and partial deafferentation. J Comp Neurol 414: 238-254.
86. Shetty AK, Turner DA. 1999b. Vulnerability of the dentate gyrus to aging and intracerebroventricular administration of kainic acid. Exp Neurol 158: 491-503.
87. Shetty AK, Turner DA. 2000. Fetal hippocampal grafts containing CA3 cells restore host hippocampal glutamate decarboxylase-positive interneuron numbers in a rat model of temporal lobe epilepsy. J Neurosci 20: 8788-8801.
88. Shetty AK, Turner DA. 2001. Glutamic acid decarboxylase-67-positive hippocampal interneurons undergo a permanent reduction in number following kainic acid-induced degeneration of ca3 pyramidal neurons. Exp Neurol 169: 276-297.
89. Shetty AK, Zaman V, Shetty GA. 2003. Hippocampal neurotrophin levels in a kainate model of temporal lobe epilepsy: A lack of correlation between brain-derived neurotrophic factor content and progression of aberrant dentate mossy fiber sprouting. J Neurochem 87: 147-159.
90. Shetty AK, Rao MS, Hattiangady B, Zaman V, Shetty GA. 2004. Hippocampal neurotrophin levels after injury: Relationship to the age of the hippocampus at the time of injury. J Neurosci Res 78: 520-532.
91. Shetty AK, Zaman V, Hattiangady B. 2005. Repair of the injured adult hippocampus through graft-mediated modulation of the plasticity of the dentate gyrus in a rat model of temporal lobe epilepsy. J Neurosci 25: 8391-8401.
92. Shetty AK, Rao MS, Hattiangady B. 2008. Behavior of hippocampal NSCs after grafting into the injured aged hippocampus. J Neurosci Res 86: 3062-3074.
93. Shetty AK, Hattiangady B, Rao MS. 2009. Vulnerability of hippocampal GABA-ergic interneurons to kainate induced excitotoxic injury during old age. J Cell Mol Med 13: 2408-2423.
94. Shors TJ, Townsend DA, Zhao M, Kozorovitskiy Y, Gould E. 2002. Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus 12: 578-584.
95. Sivilia S, Giuliani A, Del Vecchio G, Giardino L, Calza L. 2008. Age-dependent impairment of hippocampal neurogenesis in chronic cerebral hypopefusion. Neuropathol Appl Neuorbiol 34: 52-61.
96. Siwak-Tapp CT, Head E, Muggenburg BA, Milgram NW, Cotman CW. 2007. Neurogenesis decreases with age in the canine hippocampus and correlates with cognitive function. Neurobiol Learn Mem 88: 249-259.
97. Sun D, McGinn MJ, Zhou Z, Harvey HB, Bullock MR, Colello RJ. 2007. Anatomical integration of newly generated dentate granule neurons following traumatic brain injury in adult rats and its association to cognitive recovery. Exp Neurol 204: 264-272.
98. Sun Y, Jin K, Xie L, Childs J, Mao XO, Logvinova A, Greenberg DA. 2003. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest 111: 1843-1851.
99. Sun Y, Jin K, Childs JT, Xie L, Mao XO, Greenberg DA. 2006. Vascular endothelial growth factor-B (VEGFB) stimulates neurogenesis: Evidence from knockout mice and growth factor administration. Dev Biol 289: 329-335.
100. Toni N, Teng EM, Bushong EA, Aimone JB, Zhao C, Consiglio A, van Praag H, Martone ME, Ellisman MH, Gage FH. 2007. Synapse formation on neurons born in the adult hippocampus. Nat Neurosci 10: 727-734.
101. Toni N, Laplagne DA, Zhao C, Lombardi G, Ribak CE, Gage FH, Schinder AF. 2008. Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci 11: 901-907.
102. Tuszynski MH, Thal L, Pay M, Salmon DP, Hoi-Sang U, Bakay R, Patel P, Blesch A, Vahlsing HL, Ho G, Tong G, Potkin SG, Fallon J, Hansen L, Mufson EJ, Kordower JH, Gall C, Conner J. 2005. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med 11: 551-555.
103. van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH. 2002. Functional neurogenesis in the adult hippocampus. Nature 415: 1030-1034.
104. van Praag H, Shubert T, Zhao C, Gage FH. 2005. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25: 8680-8685.
105. Wang WY, Dong JH, Liu X, Wang Y, Ying GX, Ni ZM, Zhou CF. 2005. Vascular endothelial growth factor and its receptor Flk-1 are expressed in the hippocampus following entorhinal deafferentation. Neuroscience 134: 1167-1178.
106. Woods AG, Guthrie KM, Kurlawalla MA, Gall CM. 1998. Deafferentation-induced increases in hippocampal insulin-like growth factor-1 messenger RNA expression are severely attenuated in middle aged and aged rats. Neuroscience 83: 663-668.
107. Zaman V, Shetty AK. 2002. Combined neurotrophic supplementation and caspase inhibition enhances survival of fetal hippocampal CA3 cell grafts in lesioned CA3 region of the aging hippocampus. Neuroscience 109: 537-553.
108. Zaman V, Shetty AK. 2003. Fetal hippocampal CA3 cell grafts enriched with fibroblast growth factor-2 exhibit enhanced neuronal integration into the lesioned aging rat hippocampus in a kainate model of temporal lobe epilepsy. Hippocampus 13: 618-632.