Donepezil treatment restores the ability of estradiol to enhance cognitive performance in aged rats: Evidence for the cholinergic basis of the critical period hypothesis

Hormones and Behavior

Volumn 56, Issue 1, 2009, Pages 73-83

  Gibbs, R B ^a   Mauk, R ^a   Nelson, D ^a   Johnson, D A ^b  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b DUQUESNE UNIVERSITY   (United States)

Author keywords

Aging; Cholinesterase inhibitor; Critical period hypothesis; Hormone therapy; Spatial learning; Surgical menopause

Indexed keywords

CHOLINESTERASE INHIBITOR; DONEPEZIL; ESTRADIOL;

AGED; AGING; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHOLINERGIC ACTIVITY; CHOLINERGIC STIMULATION; CHOLINERGIC SYSTEM; COGNITION; CONTROLLED STUDY; DRUG MECHANISM; FEMALE; FOREBRAIN; HORMONAL REGULATION; INSTRUMENTAL CONDITIONING; LEARNING; MAZE TEST; MENTAL PERFORMANCE; NONHUMAN; OVARIECTOMY; PRIORITY JOURNAL; RAT; RESPONSE TIME; TASK PERFORMANCE;

AGING; ANIMALS; BRAIN; CHOLINE O-ACETYLTRANSFERASE; CHOLINESTERASE INHIBITORS; COGNITION; CONDITIONING, OPERANT; ESTRADIOL; ESTROGENS; FEMALE; INDANS; MAZE LEARNING; OVARIECTOMY; PIPERIDINES; RATS; RATS, SPRAGUE-DAWLEY; REACTION TIME; TIME FACTORS;

EID: 67349142096     PISSN: 0018506X     EISSN: 10956867     Source Type: Journal    
DOI: 10.1016/j.yhbeh.2009.03.003     Document Type: Article

References (107)

1. Adams M.M., Morrison J.H., and Gore A.C. N-methyl-d-aspartate receptor mRNA levels change during reproductive senescence in the hippocampus of female rats. Exp. Neurol. 170 1 (2001) 171-179
2. Altavista M.C., Rossi P., Bentivoglio A.R., Crociani P., and Albanese A. Aging is associated with a diffuse impairment of forebrain cholinergic neurons. Brain Res. 508 1 (1990) 51-59
3. Araujo D.M., Lapchak P.A., Meaney M.J., Collier B., and Quirion R. Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: relationship to presynaptic cholinergic markers and binding sites. J. Neurosci. 10 9 (1990) 3069-3078
4. Barnes C.A., Meltzer J., Houston F., Orr G., McGann K., and Wenk G.L. Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors. Neuroscience 99 1 (2000) 17-23
5. Bartus R.T. On neurodegenerative diseases, models, and treatment strategies: lessons learned and lessons forgotten a generation following the cholinergic hypothesis. Exp. Neurol. 163 2 (2000) 495-529
6. Baxter M.G., and Chiba A.A. Cognitive functions of the basal forebrain. Curr. Opin. Neurobiol. 9 2 (1999) 178-183
7. Baxter M.G., Bucci D.J., Gorman L.K., Wiley R.G., and Gallagher M. Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats. Behav. Neurosci. 109 4 (1995) 714-722
8. Bennett B.M., Reynolds J.N., Prusky G.T., Douglas R.M., Sutherland R.J., and Thatcher G.R. Cognitive deficits in rats after forebrain cholinergic depletion are reversed by a novel NO mimetic nitrate ester. Neuropsychopharmacology 32 3 (2006) 505-513
9. Bhavnani B.R. Estrogens and menopause: pharmacology of conjugated equine estrogens and their potential role in the prevention of neurodegenerative diseases such as Alzheimer's. J. Steroid Biochem. Mol. Biol. 85 2-5 (2003) 473-482
10. Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst. Rev. 1 (2006) CD005593
11. Bohacek J., Bearl A.M., and Daniel J.M. Long-term ovarian hormone deprivation alters the ability of subsequent oestradiol replacement to regulate choline acetyltransferase protein levels in the hippocampus and prefrontal cortex of middle-aged rats. J. Neuroendocrinol. 20 8 (2008) 1023-1027
12. Bradford M. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principal of protein dye binding. Anal. Biochem. 72 (1976) 248-253
13. Chappell J., McMahan R., Chiba A., and Gallagher M. A re-examination of the role of basal forebrain cholinergic neurons in spatial working memory. Neuropharmacology 37 (1998) 481-487
14. Cutuli D., Foti F., Mandolesi L., De Bartolo P., Gelfo F., Federico F., and Petrosini L. Cognitive performance of healthy young rats following chronic donepezil administration. Psychopharmacology (Berl.) 197 4 (2008) 661-673
15. Cutuli D., Foti F., Mandolesi L., De Bartolo P., Gelfo F., Federico F., and Petrosini L. Cognitive performances of cholinergically depleted rats following chronic donepezil administration. J. Alzheimers Dis. (2009). http://www.ncbi.nlm.nih.gov/pubmed/19221411?dopt=Citation http://www.ncbi.nlm.nih.gov/pubmed/19221411?dopt=Citation [Electronic publication ahead of print]
16. D'Intino G., Paradisi M., Fernandez M., Giuliani A., Aloe L., Giardino L., and Calza L. Cognitive deficit associated with cholinergic and nerve growth factor down-regulation in experimental allergic encephalomyelitis in rats. Proc. Natl. Acad. Sci. U. S. A. 102 8 (2005) 3070-3075
17. Daniel J.M. Effects of oestrogen on cognition: what have we learned from basic research?. J. Neuroendocrinol. 18 10 (2006) 787-795
18. Daniel J.M., and Dohanich G.P. Acetylcholine mediates the estrogen-induced increase in NMDA receptor binding in CA1 of the hippocampus and the associated improvement in working memory. J. Neurosci. 21 17 (2001) 6949-6956
19. Daniel J.M., Hulst J.L., and Lee C.D. Role of hippocampal M2 muscarinic receptors in the estrogen-induced enhancement of working memory. Neuroscience 132 1 (2005) 57-64
20. Daniel J.M., Hulst J.L., and Berbling J.L. Estradiol replacement enhances working memory in middle-aged rats when initiated immediately after ovariectomy but not after a long-term period of ovarian hormone deprivation. Endocrinology 147 1 (2006) 607-614
21. Davies P., and Maloney A.J.F. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 2 (1976) 1403
22. Dornan W.A., McCampbell A.R., Tinkler G.P., Hickman L.J., Bannon A.W., Decker M.W., and Gunther K.L. Comparison of site-specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG saporin. Behav. Brain Res. 82 (1996) 93-101
23. Dumas J., Hancur-Bucci C., Naylor M., Sites C., and Newhouse P. Estrogen treatment effects on anticholinergic-induced cognitive dysfunction in normal postmenopausal women. Neuropsychopharmacology 31 9 (2006) 2065-2078
24. Everitt B.J., and Robbins T.W. Central cholinergic systems and cognition. Annu. Rev. Psychol. 48 (1997) 649-684
25. Fader A.J., Hendricson A.W., and Dohanich G.P. Estrogen improves performance of reinforced t-maze alternation and prevents the amnestic effects of scopolamine administered systemically or intrahippocampally. Neurobiol. Learn. Mem. 69 3 (1998) 225-240
26. Fader A.J., Johnson P.E.M., and Dohanich G.P. Estrogen improves working but not reference memory and prevents amnestic effects of scopolamine on a radial-arm maze. Pharmacol. Biochem. Behav. 62 4 (1999) 711-717
27. Fernandez S.M., Lewis M.C., Pechenino A.S., Harburger L.L., Orr P.T., Gresack J.E., Schafe G.E., and Frick K.M. Estradiol-induced enhancement of object memory consolidation involves hippocampal extracellular signal-regulated kinase activation and membrane-bound estrogen receptors. J. Neurosci. 28 35 (2008) 8660-8667
28. Fischer W., Gage F.H., and Björklund A. Degenerative changes in forebrain cholinergic nuclei correlate with cognitive impairments in aged rats. Eur. J. Neurosci. 1 1 (1989) 34-45
29. Fischer W., Chen K.S., Gage F.H., and Bjorklund A. Progressive decline in spatial learning and integrity of forebrain cholinergic neurons in rats during aging. Neurobiol. Aging 13 1 (1992) 9-23
30. Fitz N.F., Gibbs R.B., and Johnson D.A. Selective lesion of septal cholinergic neurons in rats impairs acquisition of a delayed matching to position T-maze task by delaying the shift from a response to a place strategy. Brain Res. Bull. 77 6 (2008) 356-360
31. Frick K.M. Estrogens and age-related memory decline in rodents: what have we learned and where do we go from here?. Horm. Behav. 55 1 (2009) 2-23
32. Gabor R., Nagle R., Johnson D.A., and Gibbs R.B. Estrogen enhances potassium-stimulated acetylcholine release in the rat hippocampus. Brain Res. 962 (2003) 244-247
33. Gibbs R.B. Fluctuations in relative levels of choline acetyltransferase mRNA in different regions of the rat basal forebrain across the estrous cycle: effects of estrogen and progesterone. J. Neurosci. 16 3 (1996) 1049-1055
34. Gibbs R.B. Effects of estrogen on basal forebrain cholinergic neurons vary as a function of dose and duration of treatment. Brain Res. 757 (1997) 10-16
35. Gibbs R.B. Impairment of basal forebrain cholinergic neurons associated with aging and long-term loss of ovarian function. Exp. Neurol. 151 (1998) 289-302
36. Gibbs R.B. Estrogen replacement enhances acquisition of a spatial memory task and reduces deficits associated with hippocampal muscarinic receptor inhibition. Horm. Behav. 36 (1999) 222-233
37. Gibbs R.B. Effects of gonadal hormone replacement on measures of basal forebrain cholinergic function. Neuroscience 101 4 (2000) 931-938
38. Gibbs R.B. Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats. Neurobiol. Aging 21 (2000) 107-116
39. Gibbs R.B. Effects of aging, ovariectomy, and long-term hormone replacement on cholinergic neurons in the medial septum and nucleus basalis magnocellularis. J. Neuroendocrinol. 15 (2003) 477-485
40. Gibbs R.B. Testosterone and estradiol produce different effects on cognitive performance in male rats. Horm. Behav. 48 3 (2005) 268-277
41. Gibbs R. Preclinical data relating to estrogen's effects on cognitive performance. In: Rasgon N.L. (Ed). The effects of estrogen on brain function (2006), The Johns Hopkins University Press, Baltimore 9-45
42. Gibbs R.B. Estradiol enhances DMP acquisition via a mechanism not mediated by turning strategy but which requires intact basal forebrain cholinergic projections. Horm. Behav. 52 3 (2007) 352-359
43. NGFR and ChAT expression in the medial septum and diagonal band of Broca. Exp. Neurol. 116 (1992) 23-39
44. Gibbs R.B., and Gabor R. Estrogen and cognition: applying preclinical findings to clinical perspectives. J. Neurosci. Res. 74 (2003) 637-643
45. Gibbs R.B., and Johnson D.A. Cholinergic lesions produce task-selective effects on delayed matching to position and configural association learning related to response pattern and strategy. Neurobiol. Learn. Mem. 88 1 (2007) 19-32
46. Gibbs R.B., Wu D.-H., Hersh L., and Pfaff D.W. Effects of estrogen replacement on relative levels of ChAT, TrkA and nerve growth factor messenger RNAs in the basal forebrain and hippocampal formation of adult rats. Exp. Neurol. 129 1 (1994) 70-80
47. Gibbs R.B., Hashash A., and Johnson D.A. Effects of estrogen on potassium-evoked acetylcholine release in the hippocampus and overlying cortex of adult rats. Brain Res. 749 1 (1997) 143-146
48. Gibbs R.B., Burke A.M., and Johnson D.A. Estrogen replacement attenuates effects of scopolamine and lorazepam on memory acquisition and retention. Horm. Behav. 34 (1998) 112-125
49. Gibbs R.B., Gabor R., Cox T., and Johnson D.A. Effects of raloxifene and estradiol on hippocampal acetylcholine release and spatial learning in the rat. Psychoneuroendocrinology 29 (2004) 741-748
50. Gibson G.E., Peterson C., and Jenden D.J. Brain acetylcholine declines with senescence. Science 213 (1981) 674-676
51. Gresack J.E., Kerr K.M., and Frick K.M. Life-long environmental enrichment differentially affects the mnemonic response to estrogen in young, middle-aged, and aged female mice. Neurobiol. Learn. Mem. 88 4 (2007) 393-408
52. Haug K.H., Bogen I.L., Osmundsen H., Walaas I., and Fonnum F. Effects on cholinergic markers in rat brain and blood after short and prolonged administration of donepezil. Neurochem. Res. 30 12 (2005) 1511-1520
53. Hernandez C.M., Gearhart D.A., Parikh V., Hohnadel E.J., Davis L.W., Middlemore M.L., Warsi S.P., Waller J.L., and Terry Jr. A.V. Comparison of galantamine and donepezil for effects on nerve growth factor, cholinergic markers, and memory performance in aged rats. J. Pharmacol. Exp. Ther. 316 2 (2006) 679-694
54. Hunsaker M.R., Rogers J.L., and Kesner R.P. Behavioral characterization of a transection of dorsal CA3 subcortical efferents: comparison with scopolamine and physostigmine infusions into dorsal CA3. Neurobiol. Learn. Mem. 88 1 (2007) 127-136
55. Johnson D.A., Zambon N.J., and Gibbs R.B. Selective lesion of cholinergic neurons in the medial septum by 192 IgG-saporin impairs learning in a delayed matching to position T-maze paradigm. Brain. Res. 943 (2002) 132-141
56. Kristofiková Z., Klaschka J., Tejkalová H., and Benesová O. High-affinity choline uptake and muscarinic receptors in rat brain during aging. Arch. Gerontol. Geriatr. 15 (1992) 87-97
57. Kritzer M.F., and Kohama S.G. Ovarian hormones differentially influence immunoreactivity for dopamine beta-hydroxylase, choline acetyltransferase, and serotonin in the dorsolateral prefrontal cortex of adult rhesus monkeys. J. Comp. Neurol. 409 3 (1999) 438-451
58. Kume T., Sugimoto M., Takada Y., Yamaguchi T., Yonezawa A., Katsuki H., Sugimoto H., and Akaike A. Up-regulation of nicotinic acetylcholine receptors by central-type acetylcholinesterase inhibitors in rat cortical neurons. Eur. J. Pharmacol. 527 1-3 (2005) 77-85
59. LeBlanc A. Estrogen and Alzheimer's disease. Curr. Opin. Investig. Drugs 3 5 (2002) 768-773
60. Luine V.N. Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats. Exp. Neurol. 89 (1985) 484-490
61. Luine V.N., Jacome L.F., and Maclusky N.J. Rapid enhancement of visual and place memory by estrogens in rats. Endocrinology 144 7 (2003) 2836-2844
62. Markowska A.L., and Savonenko A.V. Effectiveness of estrogen replacement in restoration of cognitive function after long-term estrogen withdrawal in aging rats. J. Neurosci. 22 24 (2002) 10985-10995
63. Marriott L.K., and Korol D.L. Short-term estrogen treatment in ovariectomized rats augments hippocampal acetylcholine release during place learning. Neurobiol. Learn. Mem. 80 3 (2003) 315-322
64. McLay R.N., Maki P.M., and Lyketsos C.G. Nulliparity and late menopause are associated with decreased cognitive decline. J. Neuropsychiatry Clin. Neurosci. 15 2 (2003) 161-167
65. McMahan R.W., Sobel T.J., and Baxter M.G. Selective immunolesions of hippocampal cholinergic input fail to impair spatial working memory. Hippocampus 7 2 (1997) 130-136
66. Mesulam M.M., Mufson E.J., and Rogers J. Age-related shrinkage of cortically projecting cholinergic neurons: a selective effect. Ann. Neurol. 22 (1987) 31-36
67. Moore H., Stuckman S., Sarter M., and Bruno J.P. Potassium, but not atropine-stimulated cortical acetylcholine efflux, is reduced in aged rats. Neurobiol. Aging 17 4 (1996) 565-571
68. Narahashi T., Moriguchi S., Zhao X., Marszalec W., and Yeh J.Z. Mechanisms of action of cognitive enhancers on neuroreceptors. Biol. Pharm. Bull. 27 11 (2004) 1701-1706
69. O'Malley C.A., Hautamaki R.D., Kelley M., and Meyer E.M. Effects of ovariectomy and estradiol benzoate on high affinity choline uptake, ACh synthesis, and release from rat cerebral cortical synaptosomes. Brain Res. 403 (1987) 389-392
70. Packard M.G. Posttraining estrogen and memory modulation. Horm. Behav. 34 2 (1998) 126-139
71. Packard M.G., and Teather L.A. Posttraining estradiol injections enhance memory in ovariectomized rats: cholinergic blockade and synergism. Neurobiol. Learn. Mem. 68 (1997) 172-188
72. Paxinos G., and Watson C. The Rat Brain in Stereotaxic Atlas. 2nd ed. (1986), Academic Press, London
73. Perry E.K., Perry R.H., Blessed G., and Tomlinson B.E. Necropsy evidence of cholinergic deficits in senile dementia. Lancet 1 (1977) 189
74. Prickaerts J., Sik A., van der Staay F.J., de Vente J., and Blokland A. Dissociable effects of acetylcholinesterase inhibitors and phosphodiesterase type 5 inhibitors on object recognition memory: acquisition versus consolidation. Psychopharmacology (Berl.) 177 4 (2005) 381-390
75. Rapp P.R., Morrison J.H., and Roberts J.A. Cyclic estrogen replacement improves cognitive function in aged ovariectomized rhesus monkeys. J. Neurosci. 23 13 (2003) 5708-5714
76. Resnick S.M., and Henderson V.W. Hormone therapy and risk of Alzheimer disease: a critical time. JAMA 288 17 (2002) 2170-2172
77. Resnick S.M., Maki P.M., Rapp S.R., Espeland M.A., Brunner R., Coker L.H., Granek I.A., Hogan P., Ockene J.K., and Shumaker S.A. Effects of combination estrogen plus progestin hormone treatment on cognition and affect. J. Clin. Endocrinol. Metab. 91 5 (2006) 1802-1810
78. Rocca W.A., Bower J.H., Maraganore D.M., Ahlskog J.E., Grossardt B.R., de Andrade M., and Melton III L.J. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 69 11 (2007) 1074-1083
79. Rudy J.W., and Sutherland R.J. The hippocampal formation is necessary for rats to learn and remember configural discriminations. Behav. Brain Res. 34 1-2 (1989) 97-109
80. Rudy J.W., and Sutherland R.J. Configural association theory and the hippocampal formation: an appraisal and reconfiguration. Hippocampus 5 5 (1995) 375-389
81. Rylett R.J., and Schmidt B.M. Regulation of the synthesis of acetylcholine. Prog. Brain Res. 98 (1993) 161-166
82. Sarkar S.N., Huang R.Q., Logan S.M., Yi K.D., Dillon G.H., and Simpkins J.W. Estrogens directly potentiate neuronal L-type Ca2+ channels. Proc. Natl. Acad. Sci. U. S. A. 105 39 (2008) 15148-15153
83. Savonenko A.V., and Markowska A.L. The cognitive effects of ovariectomy and estrogen replacement are modulated by aging. Neuroscience 119 3 (2003) 821-830
84. Schneider L.S., Farlow M.R., Henderson V.W., and Pogoda J.M. Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer's disease. Neurology 46 6 (1996) 1580-1584
85. Sherman K.A., and Friedman E. Pre- and post-synaptic cholinergic dysfunction in aged rodent brain regions: new findings and an interpretative review. Int. J. Dev. Neurosci. 8 6 (1990) 689-708
86. Sherman K.A., Kuster J.E., Dean R.L., Bartus R.T., and Friedman E. Presynaptic cholinergic mechanisms in brain of aged rats with memory impairments. Neurobiol. Aging 2 (1981) 99-104
87. Sherwin B.B. The critical period hypothesis: can it explain discrepancies in the oestrogen-cognition literature?. J. Neuroendocrinol. 19 2 (2007) 77-81
88. Sherwin B.B., and Henry J.F. Brain aging modulates the neuroprotective effects of estrogen on selective aspects of cognition in women: a critical review. Front. Neuroendocrinol. 29 1 (2008) 88-113
89. Shumaker S.A., Legault C., Kuller L., Rapp S.R., Thal L., Lane D.S., Fillit H., Stefanick M.L., Hendrix S.L., Lewis C.E., Masaki K., and Coker L.H. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 291 24 (2004) 2947-2958
90. Sims N.R., Bowen D.M., Allen S.J., Smith C.C., Neary D., Thomas D.J., and Davison A.N. Presynaptic cholinergic dysfunction in patients with dementia. J. Neurochem. 40 2 (1983) 503-509
91. Singh M., Meyer E.M., Millard W.J., and Simpkins J.W. Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague-Dawley rats. Brain Res. 644 (1994) 305-312
92. Smith S.S., and Woolley C.S. Cellular and molecular effects of steroid hormones on CNS excitability. Clevel. Clin. J. Med. 71 Suppl. 2 (2004) S4-10
93. Solntseva E.I., Bukanova J.V., Marchenko E., and Skrebitsky V.G. Donepezil is a strong antagonist of voltage-gated calcium and potassium channels in molluscan neurons. Comp. Biochem. Physiol., C. Toxicol. Pharmacol. 144 4 (2007) 319-326
94. Spencer J.L., Waters E.M., Romeo R.D., Wood G.E., Milner T.A., and McEwen B.S. Uncovering the mechanisms of estrogen effects on hippocampal function. Front. Neuroendocrinol. 29 2 (2007) 219-237
95. Stroessner-Johnson H.M., Rapp P.R., and Amaral D.G. Cholinergic cell loss and hypertrophy in the medial septal nucleus of the behaviorally characterized aged Rhesus monkey. J. Neurosci. 12 5 (1992) 1936-1944
96. Sugimoto H., Ogura H., Arai Y., Limura Y., and Yamanishi Y. Research and development of donepezil hydrochloride, a new type of acetylcholinesterase inhibitor. Jpn. J. Pharmacol. 89 1 (2002) 7-20
97. Suzuki S., Brown C.M., and Wise P.M. Mechanisms of neuroprotection by estrogen. Endocrine 29 2 (2006) 209-215
98. Takahata K., Minami A., Kusumoto H., Shimazu S., and Yoneda F. Effects of selegiline alone or with donepezil on memory impairment in rats. Eur. J. Pharmacol. 518 2-3 (2005) 140-144
99. Takei N., Nihonmatsu I., and Kawamura H. Age-related decline of acetylcholinesterase release evoked by depolarizing stimulation. Neurosci. Lett. 101 (1989) 182-186
100. Talboom J.S., Williams B.J., Baxley E.R., West S.G., and Bimonte-Nelson H.A. Higher levels of estradiol replacement correlate with better spatial memory in surgically menopausal young and middle-aged rats. Neurobiol. Learn. Mem. 90 1 (2008) 155-163
101. Taylor L., and Griffith W.H. Age-related decline in cholinergic synaptic transmission in hippocampus. Neurobiol. Aging 14 (1993) 509-515
102. Tinkler G.P., Tobin J.R., and Voytko M.L. Effects of two years of estrogen loss or replacement on nucleus basalis cholinergic neurons and cholinergic fibers to the dorsolateral prefrontal and inferior parietal cortex of monkeys. J. Comp. Neurol. 469 4 (2004) 507-521
103. Whitehouse P.J., Price D.L., Struble R.G., Clark A.W., Coyle J.T., and DeLong M.R. Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science 215 (1982) 1237-1239
104. Woolley C.S. Acute effects of estrogen on neuronal physiology. Annu. Rev. Pharmacol. Toxicol. 47 (2007) 657-680
105. Wu D., and Hersh L.B. Choline acetyltransferase: celebrating its fiftieth year. J. Neurochem. 62 5 (1994) 1653-1663
106. Wu C.F., Bertorelli R., Sacconi M., Pepeu G., and Consolo S. Decrease of brain acetylcholine release in aging freely-moving rats detected by microdialysis. Neurobiol. Aging 9 (1988) 357-361
107. Yu B., and Hu G.Y. Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons. Eur. J. Pharmacol. 508 1-3 (2005) 15-21