Front Neuroendocrinol 27(4): 404-414

Estrogen-BDNF Interactions: Implications for Neurodegenerative Diseases

Department of Human Anatomy and Medical Neurobiology, TAMU Health Science Center, College Station, TX 77843-1114

Correspondence to Farida Sohrabji, 228 Reynolds Medical Building, Department of Neuroscience and Experimental Therapeutics, TAMU Health Science Center, College Station TX 77843-1114, Phone: 979-845-4072, Fax: 979-845-0790, Email: ude.umat@ijbarhos-f

Publisher's Disclaimer

Abstract

Since its’ discovery over 20 years ago, BDNF has been shown to play a key role in neuronal survival, in promoting neuronal regeneration following injury, regulating transmitter systems and attenuating neural-immune responses. Estrogen’s actions in the young and mature brain, and its role in neurodegenerative diseases in many cases overlaps with those observed for BDNF. Reduced estrogen and BDNF are observed in patients with Parkinson’s disease and Alzheimer’s disease, while high estrogen levels are a risk factor for development of multiple sclerosis. Estrogen receptors, which transduce the actions of estrogen, colocalize to cells that express BDNF and its receptor trkB, and estrogen further regulates the expression of this neurotrophin system. This review describes the distribution of BDNF and trkB expressing cells in the forebrain, and the roles of estrogen and the BDNF/trkB neurotrophin system in Parkinson’s disease, Alzheimer’s disease and multiple sclerosis.

Abstract

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Footnotes

References

1. Alderson R, Alterman A, Barde Y-A, Lindsay RBrain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture. Neuron. 1990;5:297–306.[PubMed][Google Scholar]
2. Allen A, McCarson KEstrogen increases nociception-evoked brain-derived neurotrophic factor gene expression in the female rat. Neuroendocrinol. 2005;81:193–199.[PubMed][Google Scholar]
3. Altar C, Cai N, Bliven T, Juhasz M, Conner J, Acheson A, Lindsay R, Wiegand SAnterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature. 1997;389:856–860.[PubMed][Google Scholar]
4. Bansil S, Lee H, Jindal S, Holtz C, Cook SCorrelation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis. Acta Neurol. Scand. 1999;99:91–94.[PubMed][Google Scholar]
5. Barde Y-A, Edgar D, Thoenen HPurification of a new neurotrophic factor from mammalian brain. EMBO J. 1982;1:549–553.[Google Scholar]
6. Batchelor P, Liberatore G, Wong J, Porritt M, Frerichs F, Donnan G, Howells DActivated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J. Neurosci. 1999;19:1708–1716.[Google Scholar]
7. Bayas A, Hummel V, Kallmann B, Karch C, Toyka K, Rieckmann PHuman cerebral endothelial cells are a potential source for bioactive BDNF. Cytokine. 2002;19:55–58.[PubMed][Google Scholar]
8. Becker JDirect effect of 17 beta-estradiol on striatum: sex differences in dopamine release. Synapse. 1990;5:157–164.[PubMed][Google Scholar]
9. Bedard P, Langelier P, Villeneuve AOestrogens and extrapyramidal system. Lancet. 1977;2:1367–1368.[PubMed][Google Scholar]
10. Bergman E, Fundin B, Ulfhake BEffects of aging and axotomy on the expression of neurotrophin receptors in primary sensory neurons. J. Comp. Neurol. 1999;410:368–386.[PubMed][Google Scholar]
11. Bimonte-Nelson H, Nelson M, Granholm A-CProgesterone counteracts estrogen-induced increases in neurotrophins in the aged female rat brain. Neuroreport. 2004;15:2659–2663.[PubMed][Google Scholar]
12. Bishop J, Simpkins JEstradiol enhances brain glucose uptake in ovariectomized rats. Brain Res. Bull. 1995;36:315–320.[PubMed][Google Scholar]
13. Blurton-Jones M, Kuan P, Tuszynski MAnatomical evidence for transsynaptic influences of estrogen on brain-derived neurotrophic factor expression. J. Comp. Neurol. 2004;468:347–360.[PubMed][Google Scholar]
14. Caleo M, Medini P, von Bartheld C, Maffei LProvision of brain-derived neurotrophic factor via anterograde transport from the eye preserves the physiological responses of axotomized geniculate neurons. J. Neurosci. 2003;23:287–296.[Google Scholar]
15. Callier S, Morissette M, Grandbois M, Di Paolo TStereospecific prevention by 17β-estradiol of MPTP-induced dopamine depletion in mice. Synapse. 2000;37:245–251.[PubMed][Google Scholar]
16. Cavus I, Duman RInfluence of estradiol, stress, and 5-HT2A agonist treatment on brain-derived neurotrophic factor expression in female rats. Biol. Psychiatry. 2003;54:59–69.[PubMed][Google Scholar]
17. Chi O, Liu X, Weiss H. Horm. Metab. Res. 2002;34:530–534.[PubMed]
18. Chi O, Barsoum S, Wen Y, Liu X, Weiss H17beta-estradiol prevents blood-brain barrier disruption induced by VEGF. Horm. Metab. Res. 2004;36:272–276.[PubMed][Google Scholar]
19. Chi O, Hunter C, Liu X, Weiss HEffects of VEGF and nitric oxide synthase inhibition on blood-brain barrier disruption in the ischemic and non-ischemic cerebral cortex. Neurol. Res. 2005;27:864–868.[PubMed][Google Scholar]
20. Collier T, Ling Z, Carvey P, Fletcher-Turner A, Yurek D, Sladek J, Jr, Kordower JStriatal trophic factor activity in aging monkeys with unilateral MPTP-induced parkinsonism. Exp. Neurol. 2005;191:S60–S67.[PubMed][Google Scholar]
21. Condorelli D, Salin T, Dell’ A, Mudo G, Corsaro M, Timmusk T, Metsis M, Belluardo NNeurotrophins and their trk receptors in cultured cells of the glial lineage and in white matter of the central nervous system. J. Mol. Neurosci. 1995;6:237–248.[PubMed][Google Scholar]
22. Connor B, Young D, Yan Q, Faull R, Synek B, Dragunow MBrain-derived neurotrophic factor is reduced in Alzheimer’s disease. Mol. Brain Res. 1997;49:71–81.[PubMed][Google Scholar]
23. Croll S, Ip N, Lindsay R, Wiegand SExpression of BDNF and trkB as a function of age and cognitive performance. Brain Res. 1998;812:200–208.[PubMed][Google Scholar]
24. Currie L, Harrison M, Trugman J, Bennett J, Wooten FPostmenopausal estrogen use affects risk for Parkinson disease. Arch. Neurol. 2004;61:886–888.[PubMed][Google Scholar]
25. Curtis R, Adryan K, Stark J, Park J, Compton D, Weskamp G, Huber L, Chao M, Jaenisch R, Lee KDifferential role of the low affinity neurotrophin receptor (p75) in retrograde axonal transport of the neurotrophins. Neuron. 1995;14:1201–1211.[PubMed][Google Scholar]
26. Davies A, Thoenen H, Barde Y-AThe response of chick sensory neurons to brain-derived neurotrophic factor. J. Neurosci. 1986;6:1897–1904.[Google Scholar]
27. DiStefano P, Friedman B, Radziejewski C, Alexander C, Boland P, Schick C, Lindsay R, Wiegand SThe neurotrophins BDNF, NT-3, and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons. Neuron. 1992;8:983–993.[PubMed][Google Scholar]
28. Dluzen D, McDermott J, Liu BEstrogen as a neuroprotectant against MPTP-Induced neurotoxicity in C57/B1 mice. Neurotoxicol. Teratol. 1996;18:603–606.[PubMed][Google Scholar]
29. Dluzen D, McDermott JDevelopmental and genetic influences upon gender differences in methamphetamine-induced nigrostriatal dopaminergic neurotoxicity. Ann. NY Acad. Sci. 2004;1025:205–220.[PubMed][Google Scholar]
30. Donovan M, Miranda R, Kraemer R, McCaffrey T, Tessarollo L, Mahadeo D, Sharif S, Kaplan D, Tsoulfas P, Parada L. Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regulation of expression in response to injury. Am. J. Pathol. 1995;147:309–324.
31. Dougherty KD, Dreyfus CF, Black IBBrain-derived neurotrophic factor in astrocytes, oligodendrocytes, and microglia/macrophages after spinal cord injury. Neurobiol. Dis. 2000;7:574–585.[PubMed][Google Scholar]
32. Dreyfus C, Dai X, Lercher L, Racey B, Friedman W, Black IExpression of neurotrophins in the adult spinal cord in vivo. J. Neurosci. Res. 1999;56:1–7.[PubMed][Google Scholar]
33. Espeland M, Rapp S, Shumaker S, Brunner R, Manson J, Sherwin B, Hsia J, Margolis K, Hogan P, Wallace R, Dailey M, Freeman R, Hays JConjugated equine estrogens and global cognitive function in postmenopausal women. JAMA. 2004;291:2959–2968.[PubMed][Google Scholar]
34. Ferrer I, Marin X, Rey M, Ribalta T, Goutan E, Blanco R, Tolosa E, Marti E. BDNF and full-length truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies. J. Neuropath. Exp. Neurol. 1999;58:729–739.[PubMed]
35. Fuller PThe steroid receptor superfamily: mechanisms of diversity. FASEB J. 1991;5:3092–3099.[PubMed][Google Scholar]
36. Gammal E, Zuk AEffect of ethinyl estradiol on endothelial permeability to 125I-labeled albumin in female rats. Exp. Mol. Pathol. 1980;32:91–101.[PubMed][Google Scholar]
37. Gibbs RLevels of trkA and BDNF mRNA, but not NGF mRNA, fluctuate across the estrous cycle and increase in response to acute hormone replacement. Brain Res. 1998;787:259–268.[PubMed][Google Scholar]
38. Gibbs RTreatment with estrogen and progesterone affects relative levels of brain-derived neurotrophic factor mRNA and protein in different regions of the adult rat brain. Brain Res. 1999;844:20–27.[PubMed][Google Scholar]
39. Gielen A, Khademi M, Muhallab S, Olsson T, Piehl FIncreased brain-derived neurotrophic factor expression in white blood cells of relapsing-remitting multiple sclerosis patients. Scand. J. Immunol. 2003;57:493–497.[PubMed][Google Scholar]
40. Giladi N, Honigman S, Mizuta E, Kuno SHormones and Parkinson’s disease. Neurol. 1995;45:1028–1029.[PubMed][Google Scholar]
41. Gooney M, Messaoudi E, Maher F, Bramham C, Lynch MBDNF-induced LTP in dentate gyrus is impaired with age: analysis of changes in cell signaling events. Neurobiol. Aging. 2004;25:1323–1331.[PubMed][Google Scholar]
42. Grandbois M, Morissette M, Callier S, Di Paolo TOvarian steroids and raloxifene prevent MPTP-induced dopamine depletion in mice. Neuroreport. 2000;11:343–346.[PubMed][Google Scholar]
43. Gravel C, Gotz R, Lorrain A, Sendtner MAdenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons. Nature Med. 1997;3:765–770.[PubMed][Google Scholar]
44. Hartikka J, Hefti FDevelopment of septal cholinergic neurons in culture: plating density and glial cells modulate effects of NGF on survival, fiber growth, and expression of transmitter-specific enzymes. J. Neurosci. 1988;8:2967–2985.[Google Scholar]
45. Helfert R, Sommer T, Meeks J, Hofstetter P, Hughes LAge-related synaptic changes in the central nucleus of the inferior colliculus of Fischer-344 rats. J. Comp. Neurol. 1999;406:285–298.[PubMed][Google Scholar]
46. Hock C, Heese K, Hulette C, Rosenberg C, Otten URegion-specific neurotrophin imbalances in Alzheimer disease. Arch. Neurol. 2000;57:846–851.[PubMed][Google Scholar]
47. Hofer M, Barde Y-ABrain-derived neurotrophic factor prevents neuronal death in vivo. Nature. 1988;331:261–262.[PubMed][Google Scholar]
48. Hofer M, Pagliusi S, Hohn A, Leibrock J, Barde Y-ARegional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J. 1990;9:2459–2464.[Google Scholar]
49. Hoffman G, Le W, Murphy A, Koski CDivergent effects of ovarian steroids on neuronal survival during experimental allergic encephalitis in Lewis rats. Exp. Neurol. 2001;171:272–282.[PubMed][Google Scholar]
50. Holsinger R, Schnarr J, Henry P, Castelo V, Fahnestock MQuantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: decreased levels in Alzheimer’s disease. Mol. Brain Res. 2000;76:347–354.[PubMed][Google Scholar]
51. Hyman C, Hofer M, Barde Y-A, Juhasz M, Yancopoulos G, Squinto S, Lindsay RBDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature. 1991;350:230–232.[PubMed][Google Scholar]
52. Hyman C, Juhasz M, Jackson C, Wright P, Ip N, Lindsay ROverlapping and distinct actions of the neurotrophins BDNF, NT-3, and NT-4/5 on cultured dopaminergic and GABAergic neurons of the ventral mesencephalon. J. Neurosci. 1994;14:335–347.[Google Scholar]
53. Ignar-Trowbridge D, Nelson K, Bidwell M, Curtis S, Washburn T, McLachlan J, Korach KCoupling of dual signaling pathways: epidermal growth factor action involves the estrogen receptor. Proc. Natl. Acad. Sci. USA. 1992;89:4658–4662.[Google Scholar]
54. Imamura K, Hishikawa N, Ono K, Suzuki H, Sawada M, Nagatsu T, Yoshida M, Hashizume YCytokine production of activated microglia and decrease in neurotrophic factors of neurons in the hippocampus of Lewy body disease brains. Acta Neuropathol. 2005;109:141–150.[PubMed][Google Scholar]
55. Ivanova T, Kuppers E, Engele J, Cordian BEstrogen stimulates brain-derived neurotrophic factor expression in embryonic mouse midbrain neruons through a membrane-mediated and calcium-dependent mechanism. J. Neurosci. Res. 2001;66:221–230.[PubMed][Google Scholar]
56. Jansson L, Olsson T, Holmdahl REstrogen induces a potent suppression of experimental autoimmune encephalomyelitis and collagen-induced arthritis in mice. J. Neuroimmunol. 1994;53:203–207.[PubMed][Google Scholar]
57. Jezierski M, Sohrabji FRegion- and peptide-specific regulation of the neurotrophins by estrogen. Mol. Brain Res. 2000;85:77–84.[PubMed][Google Scholar]
58. Jezierski M, Sohrabji FNeurotrophin expression in the reproductively senescent forebrain is refractory to estrogen stimulation. Neurobiol. Aging. 2001;22:309–319.[PubMed][Google Scholar]
59. Jezierski M, Sohrabji FEstrogen enhances retrograde transport of brain-derived neurotrophic factor in the rodent forebrain. Endocrinol. 2003;144:5022–5029.[PubMed][Google Scholar]
60. Johnson H, Hokfelt T, Ulfhake BExpression of _p75, trkB and trkC in nonmanipulated and axotomized motoneurons of aged rats. Mol. Brain Res. 1999;69:21–34.[PubMed][Google Scholar]
61. Johnson J, Barde Y-A, Schwab M, Thoenen HBrain-derived neurotrophic factor supports the survival of cultured rat retinal ganglion cells. J. Neurosci. 1986;6:3031–3038.[Google Scholar]
62. Kenny P, File S, Rattray MAcute nicotine decreases, and chronic nicotine increases the expression of brain-derived neurotrophic factor mRNA in rat hippocampus. Brain Res. Mol. Brain Res. 2000;85[PubMed][Google Scholar]
63. Kerschensteiner M, Gallmeier E, Behrens L, Leal V, Misgeld T, Klinkert W, Kolbeck R, Hoppe E, Oropeza-Wekerle R-L, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld RActivated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: A neuroprotective role of inflammation? J. Exp. Med. 1999;189:865–870.[Google Scholar]
64. Knusel B, Winslow J, Rosenthal A, Burton L, Seid D, Nikolics K, Hefti FPromotion of central cholinergic and dopaminergic neuron differentiation by brain-derived neurotrophic factor but not neurotrophin 3. Proc. Natl. Acad. Sci. USA. 1991;88:961–965.[Google Scholar]
65. Knusel B, Beck K, Winslow J, Rosenthal A, Burton L, Widmer H, Nikolics K, Hefti FBrain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain. J. Neurosci. 1992;12:4391–4402.[Google Scholar]
66. Krizsan-Agbas D, Pedchenko T, Hasan W, Smith POestrogen regulates sympathetic neurite outgrowth by modulating brain derived neurotrophic factor synthesis and release by the rodent uterus. Eur. J. Neurosci. 2003;18:2760–2768.[PubMed][Google Scholar]
67. Lapchak P, Araujo D, Beck K, Finch C, Johnson S, Hefti FBDNF and trkB mRNA expression in the hippocampal formation of aging rats. Neurobiol. Aging. 1993;14:121–126.[PubMed][Google Scholar]
68. Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde Y-AMolecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989;341:149–152.[PubMed][Google Scholar]
69. Leranth C, Roth R, Elsworth J, Naftolin F, Horvath T, Redmond D., Jr Estrogen is essential for maintaining nigrostriatal dopamine neurons in primates: implications for Parkinson’s disease and memory. J. Neurosci. 2000;20:8604–8609.
70. Levesque D, Di Paolo TModulation by estradiol and progesterone of the GTP effect on striatal D-2 dopamine receptors. Biochem. Pharmacol. 1993;45:723–733.[PubMed][Google Scholar]
71. Lindsay R, Thoenen H, Barde Y-APlacode and neural crest-derived sensory neurons are responsive at early developmental stages to brain-derived neurotrophic factor. Dev. Biol. 1985;112:319–328.[PubMed][Google Scholar]
72. Lindsay RNerve growth factors (NGF, BDNF) enhance axonal regeneration but are not required for survival of adult sensory neurons. J. Neurosci. 1988;8:2394–2405.[Google Scholar]
73. Liu H, Buenafe A, Matejuk A, Ito A, Zamora A, Dwyer J, Vandenbark A, Offner HEstrogen inhibition of EAE involves effects on dendritic cell function. J. Neurosci. Res. 2002;70:238–248.[PubMed][Google Scholar]
74. Liu Y, Fowler C, Young L, Yan Q, Insel T, Wang ZExpression and estrogen regulation of brain-derived neurotrophic factor gene and protein in the forebrain of female prairie voles. J. Comp. Neurol. 2001;433:499–514.[PubMed][Google Scholar]
75. Maier S, West JDrinking patterns and alcohol-related birth defects. Alcohol Res. Health. 2001;25:168–174.[Google Scholar]
76. Malkovska I, Kernie S, Parada LDifferential expression of the four untranslated BDNF exons in the adult mouse brain. J. Neurosci. Res. 2006;83:211–221.[PubMed][Google Scholar]
77. Masana Y, Wanaka A, Kato H, Asai T, Tohyama MLocalization of trkB mRNA in postnatal brain development. J. Neurosci. Res. 1993;35:468–479.[PubMed][Google Scholar]
78. Matejuk A, Hopke C, Vandenbark A, Hurn P, Offner HMiddle-age male mice have increased severity of experimental autoimmune encephalomyelitis and are unresponsive to testosterone therapy. J. Immunol. 2005;174:2387–2395.[PubMed][Google Scholar]
79. Merlio J-P, Ernfors P, Jaber M, Persson HMolecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system. Neurosci. 1992;51:513–532.[PubMed][Google Scholar]
80. Michalski B, Fahnestock MPro-brain derived neurotrophic factor is decreased in parietal cortex in Alzheimer’s disease. Mol. Brain Res. 2003;111:148–154.[PubMed][Google Scholar]
81. Miller D, Ali S, O’Callaghan J, Laws SThe impact of gender and estrogen on striatal dopaminergic neurotoxicity. Ann. NY Acad. Sci. 1998;844:153–165.[PubMed][Google Scholar]
82. Miranda R, Sohrabji F, Toran-Allerand CNeuronal colocalization of mRNAs for neurotrophins and their receptors in the developing central nervous system suggests a potential for autocrine interactions. Proc. Natl. Acad. Sci. USA. 1993;90:6439–6443.[Google Scholar]
83. Miwa T, Furukawa S, Nakajima K, Furukawa Y, Kohsaka SLipopolysaccharide enhances synthesis of brain-derived neurotrophic factor in cultured rat microglia. J. Neurosci. Res. 1997;50:1023–1029.[PubMed][Google Scholar]
84. Mogi M, Togari A, Kondo T, Mizuno Y, Komure O, Kuno S, Ichinose H, Nagatsu TBrain-derived neurotrophic factor and nerve-growth factor concentrations are decreased in the substantia nigra in Parkinson’s disease. Neurosci. Lett. 1999;270:45–48.[PubMed][Google Scholar]
85. Morse J, Wiegand S, Anderson K, You Y, Cai N, Carnahan J, Miller J, DiStefano P, Altar C, Lindsay RBrain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection. J. Neurosci. 1993;13:4146–4156.[Google Scholar]
86. Mulnard R, Cotman C, Kawas C, van Dyck C, Sano M, Doody R, Koss E, Pfeiffer E, Jin S, Gamst A, Grundman M, Thomas R, Thal LEstrogen replacement therapy for treatment of mild to moderate Alzheimer disease. JAMA. 2000;283:1007–1015.[PubMed][Google Scholar]
87. Murray K, Gall C, Jones E, Isackson PDifferential regulation of brain-derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase messenger RNA expression in Alzheimer’s disease. Neurosci. 1994;60:37–48.[PubMed][Google Scholar]
88. Nakahashi T, Fujimura H, Altar C, Li J, Kambayashi J.-i., Tandon N, Sun BVascular endothelial cells synthesize and secrete brain-derived neurotrophic factor. FEBS. 2000;470:113–117.[PubMed][Google Scholar]
89. Narisawa-Saito M, Wakabayashi K, Takahashi H, Nawa HRegional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer’s disease. Neuroreport. 1996;7:2925–2928.[PubMed][Google Scholar]
90. Nausieda P, Koller W, Weiner W, Klawans HChorea induced by oral contraceptives. Neurol. 1979;29:1605–1609.[PubMed][Google Scholar]
91. Neumann H, Misgeld T, Matsumuro K, Wekerle HNeurotrophins inhibit major histocompatibility class II inducibility of microglia: involvement of the p75 neurotrophin receptor. Proc. Natl. Acad. Sci. USA. 1998;95:5779–5784.[Google Scholar]
92. Paganini-Hill A, Henderson VEstrogen replacement therapy and risk of Alzheimer disease. Arch. Intern. Med. 1996;156:2213–2217.[PubMed][Google Scholar]
93. Palaszynski K, Liu H, Loo K, Voskuhl REstriol treatment ameliorates disease in males with experimental autoimmune encephalomyelitis: implications for multiple sclerosis. J. Neuroimmunol. 2004;149:84–89.[PubMed][Google Scholar]
94. Parain K, Murer M, Yan Q, Faucheux B, Aid Y, Hirsch E, Raisman-Vozari RReduced expression of brain-derived neurotrophic factor protein in Parkinson’s disease substantia nigra. Neuroreport. 1999;10:557–561.[PubMed][Google Scholar]
95. Pasqualini C, Olivier V, Guibert B, Frain O, Leviel VAcute stimulatory effect of estradiol on striatal dopamine synthesis. J. Neurochem. 1995;65:1651–1657.[PubMed][Google Scholar]
96. Pettersson A, Ciumas C, Chirsky V, Link H, Huang Y-M, Xiao B-GDendritic cells exposed to estrogen in vitro exhibit therapeutic effects in ongoing experimental allergic encephalomyelitis. J. Neuroimmunol. 2004;156:58–65.[PubMed][Google Scholar]
97. Phillips H, Hains J, Laramee G, Rosenthal A, Winslow JWidespread expression of BDNF but not NT-3 by target areas of basal forebrain cholinergic neurons. Science. 1990;250:290–294.[PubMed][Google Scholar]
98. Phillips H, Hains J, Armanini M, Laramee G, Johnson S, Winslow JBDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron. 1991;7:695–702.[PubMed][Google Scholar]
99. Pozzilli C, Falaschi P, Mainero C, Martocchia A, D’Urso R, Proietta A, Frontoni M, Bastianello S, Filippi MMRI in multiple sclerosis during the menstrual cycles; relationship with sex hormone patterns. Neurol. 1999;53:622–624.[PubMed][Google Scholar]
100. Purcell W, Westgate C, Atterwill CRat brain mast cells: an in vitro paradigm for assessing the toxic effects of neurotropic therapeutics. Neurotoxicol. 1996;17:845–850.[PubMed][Google Scholar]
101. Quinn N, Marsden CMenstrual-related fluctuations in Parkinson’s disease. Mov. Disord. 1986;1:85–87.[PubMed][Google Scholar]
102. Rasika S, Alvarez-Buylla A, Nottebohm FBDNF mediates the effects of testosterone on the survival of new neurons in an adult brain. Neuron. 1999;22:53–62.[PubMed][Google Scholar]
103. Raub T, Kuentzel S, Sawada GPermeability of bovine brain microvessel endothelial cells in vitro: barrier tightening by a factor released from astroglioma cells. Exp. Cell. Res. 1992;199:330–340.[PubMed][Google Scholar]
104. Reid A, Teasdale G, McCulloch JHormonal influence on water permeability across the blood-brain barrier. Clin. Exp. Neurol. 1983;19:50–53.[PubMed][Google Scholar]
105. Riley C, Cope T, Buck CCNS neurotrophins are biologically active and expressed by multiple cell types. J. Mol. Histol. 2004;35:771–783.[PubMed][Google Scholar]
106. Roy E, Buyer D, Licari VEstradiol in the striatum: effects on behavior and dopamine receptors but no evidence for membrane steroid receptors. Brain Res. Bull. 1990;25:221–227.[PubMed][Google Scholar]
107. Salehi A, Verhaagen J, Dijkhuizen P, Swaab DCo-localization of high-affinity neurotrophin receptors in nucleus basalis of Meynert neurons and their differential reduction in Alzheimer’s disease. Neurosci. 1996;75:373–387.[PubMed][Google Scholar]
108. Sandyk REstrogens and the pathophysiology of Parkinson’s disease. Intern. J. Neurosci. 1989;45:119–122.[PubMed][Google Scholar]
109. Sato T, Wilson T, Hughes L, Konrad H, Nakayama M, Helfert RAge-related changes in levels of tyrosine kinase B receptor and fibroblast growth factor receptor 2 in the rat inferior colliculus: implications for neural senescence. Neurosci. 2001;103:695–702.[PubMed][Google Scholar]
110. Secor V, Secor W, Gutekunst C, Brown MMast cells are essential for early onset and severe disease in a murine model of multiple sclerosis. J. Exp. Med. 2000;191:813–822.[Google Scholar]
111. Sendtner M, Holtmann B, Kolbeck R, Thoenen H, Barde YBrain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature. 1992;360:757–759.[PubMed][Google Scholar]
112. Sherwin BEstrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Psychoneuroendo. 1988;13:345–357.[PubMed][Google Scholar]
113. Shi J, Zhang Y, Simpkins JEffects of 17beta-estradiol on glucose transporter 1 expression and endothelial cell survival following focal ischemia in the rats. Exp. Brain Res. 1997;117:200–206.[PubMed][Google Scholar]
114. Shumaker S, Legault C, Rapp S, Thal L, Wallace R, Ockene J, Hendrix S, Jones B, III, Assaf A, Jackson R, Kotchen J, Wassertheil-Smoller S, Wactawski-Wende J. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The women’s health initiatitive memory study: a randomized controlled trial. JAMA. 2003;289:2651–2662.[PubMed]
115. Singh M, Meyer E, Simpkins JThe 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. Endocrinol. 1995;136:2320–2324.[PubMed][Google Scholar]
116. Singh M, Setalo G, Guan X, Warren M, Toran-Allerand CEstrogen-induced activation of mitogen-activated protein kinase in cerebral cortical explants: convergence of estrogen and neurotrophin signaling pathways. J. Neurosci. 1999;19:1179–1188.[Google Scholar]
117. Sohrabji F, Miranda R, Toran-Allerand CIdentification of a putative estrogen response element in the gene coding for BDNF. Proc. Natl. Acad. Sci. USA. 1995;92:11110–11114.[Google Scholar]
118. Solum D, Handa REstrogen regulates the development of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus. J. Neurosci. 2002;22:2650–2659.[Google Scholar]
119. Stadelmann C, Kerschensteiner M, Misgeld T, Bruck W, Hohlfeld R, Lassmann HBDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain. 2002;125:75–85.[PubMed][Google Scholar]
120. Stoeckel K, Thoenen HRetrograde axonal transport of nerve growth factor: specificity and biological importance. Brain Res. 1975;85:337–341.[PubMed][Google Scholar]
121. Strijks E, Kremer J, Horstink MEffects of female sex steroids on Parkinson’s disease in postmenopausal women. Clin. Neuropharm. 1999;22:93–97.[PubMed][Google Scholar]
122. Sun M, Alkon DDifferential gender-related vulnerability to depression induction and converging antidepressant responses in rats. J. Pharmacol. Exp. Ther. 2006;316:926–932.[PubMed][Google Scholar]
123. Takao T, Flint N, Lee L, Ying X, Merrill J, Chandross K17beta-estradiol protects oligodendrocytes from cytotoxicity induced cell death. J. Neurochem. 2004;89:660–673.[PubMed][Google Scholar]
124. Takayama N, Ueda HMorphine-induced chemotaxis and brain-derived neurotrophic factor expression in microglia. J. Neurosci. 2005;25:430–435.[Google Scholar]
125. Tang M-X, Jacobs D, Stern Y, Marder K, Schofield P, Gurland B, Andrews H, Mayeux REffect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet. 1996;348:429–432.[PubMed][Google Scholar]
126. Thanos S, Bahr M, Barde Y-A, Vanselow JSurvival and axonal elongation of adult rat retinal ganglion cells In vitro effects of lesioned sciatic nerve and brain derived neurotrophic factor. Eur. J. Neurosci. 1989;1:19–26.[PubMed][Google Scholar]
127. Theoharides T, Dimitriadou V, Letourneau R, Rozniecki J, Vliagoftis H, Boucher WSynergistic action of estradiol and myelin basic protein on mast cell secretion and brain myelin changes resembling early stages of demyelination. Neurosci. 1993;57:861–871.[PubMed][Google Scholar]
128. Thorogood M, Hannaford PThe influence of oral contraceptives on the risk of multiple sclerosis. Br. J. Obstet. Gynaecol. 1998;105:1296–1299.[PubMed][Google Scholar]
129. Vanderboom R, Sheffield LEstrogen enhances epidermal growth factor-induced DNA synthesis in mammary epithelial cells. J. Cell. Physiol. 1993;156:367–372.[PubMed][Google Scholar]
130. Viant M, Millam J, Delany M, Fry DRegulation of brain-derived neurotrophic factor messenger RNA levels in avian hypothalamic slice cultures. Neurosci. 2000;99:373–380.[PubMed][Google Scholar]
131. Wang Q, Zheng JcAMP-mediated regulation of neurotrophin-induced collapse of nerve growth cones. J. Neurosci. 1998;18[Google Scholar]
132. Watson F, Heerssen H, Moheban D, Lin M, Sauvageot C, Bhattacharyya A, Pomeroy S, Segal RRapid nuclear responses to target-derived neurotrophins require retrograde transport of ligand-receptor complex. J. Neurosci. 1999;19:7889–7900.[Google Scholar]
133. West A, Chen W, Dalva M, Dolmetsch R, Kornhauser J, Shaywitz A, Takasu M, Tao X, Greenberg MCalcium regulation of neuronal gene expression. Proc. Natl. Acad. Sci. USA. 2001;98[Google Scholar]
134. Wetmore C, Ernfors P, Persson H, Olson LLocalization of brain-derived neurotrophic factor mRNA to neurons in the brain by in situ hybridization. Exp. Neurol. 1990;109:141–152.[PubMed][Google Scholar]
135. Wetmore C, Cao Y, Pettersson R, Olson LBrain-derived neurotrophic factor: subcellular compartmentalization and interneuronal transfer as visualized with anti-peptide antibodies. Proc. Natl. Acad. Sci. USA. 1991;88:9843–9847.[Google Scholar]
136. Wolburg H, Neuhaus J, Kniesel U, Krauss B, Schmid E, Ocalan M, Farrell C, Risau W. Modulation of tight junction structure in blood-brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes. J. Cell. Sci. 1994;107:1347–1357.[PubMed]
137. Wong V, Arriaga R, Ip N, Lindsay RThe neurotrophins BDNF, NT-3, and NT-4/5, but not NGF, up-regulate the cholinergic phenotype of developing motor neurons. Eur. J. Neurosci. 1993;5:466–474.[PubMed][Google Scholar]
138. Wu H, Friedman W, Dreyfus CDifferential regulation of neurotrophin expression in basal forebrain astroctyes by neuronal signals. J. Neurosci. 2004;76:76–85.[PubMed][Google Scholar]
139. Xu X, Guenard V, Kleitman N, Aebischer P, Bunge MA combination of BDNF and NT-3 promotes supraspinal axonal regeneration into schwann cell grafts in adult rat thoracic spinal cord. Exp. Neurol. 1995;134:261–272.[PubMed][Google Scholar]
140. Yamamoto H, Gurney MHuman platelets contain brain-derived neurotrophic factor. J. Neurosci. 1990;10:3469–3478.[Google Scholar]
141. Yan Q, Elliott J, Snider WBrain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature. 1992;360:753–755.[PubMed][Google Scholar]
142. Yan Q, Zheng S, Yan SPrenatal cocaine exposure decreases brain-derived neurotrophic factor proteins in the rat brain. Brain Res. 2004;1009:228–233.[PubMed][Google Scholar]
143. Ye J-H, Houle JTreatment of the chronically injured spinal cord with neurotrophic factors can promote axonal regeneration from supraspinal neurons. Exp. Neurol. 1997;143:70–81.[PubMed][Google Scholar]
144. Yu I, Lee S, Lee Y, Son HDifferential effects of corticosterone and dexamethasone on hippocampal neurogenesis in vitro. Biochem. Biophys. Res. Comm. 2004;317:484–490.[PubMed][Google Scholar]
145. Yu L, Liao PEstrogen and progesterone distinctively modulate methamphetamine-induced dopamine and serotonin depletions in C57BL/J6 mice. J. Neural Transm. 2000;107:1139–1147.[PubMed][Google Scholar]
146. Zandi P, Carlson M, Plassman B, Welsh-Bohmer K, Mayer L, Steffens D, Breitner JHormone replacement therapy and incidence of Alzheimer disease in older women. JAMA. 2002;288:2123–2129.[PubMed][Google Scholar]
147. Zhou J, Zhang H, Cohen R, Pandey SEffects of estrogen treatment on expression of brain-derived neurotrophic factor and cAMP response element-binding protein expression and phosphorylation in rat amygdaloid and hippocampal structures. Neuroendocrinol. 2005;81:294–310.[Google Scholar]
148. Ziylan Y, Lefauconnier J, Bernard G, Bourre JBlood-brain barrier permeability: regional alterations after acute and chronic administration of ethinyl estradiol. Neurosci. Lett. 1990;118:181–184.[PubMed][Google Scholar]