Role of estrogen receptor α and β in preserving hippocampal function during aging

Journal of Neuroscience

Volumn 33, Issue 6, 2013, Pages 2671-2683

  Han, Xiaoxia ^a   Aenlle, Kristina K ^b   Bean, Linda A ^a   Rani, Asha ^a   Semple Rowland, Susan L ^a   Kumar, Ashok ^a   Foster, Thomas C ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ESTRADIOL; ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA;

AGE; AGING; ANIMAL EXPERIMENT; ARTICLE; BEHAVIOR; CONTROLLED STUDY; FEMALE; GENE EXPRESSION; GENETIC TRANSCRIPTION; HIPPOCAMPUS; KNOCKOUT MOUSE; LEARNING; MAZE TEST; MEMORY; MOUSE; NONHUMAN; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TASK PERFORMANCE; TISSUE MICROARRAY; TRAINING; UTERUS WEIGHT;

AGING; ANIMALS; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; FEMALE; HIPPOCAMPUS; MAZE LEARNING; MICE; MICE, KNOCKOUT;

EID: 84873314741     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.4937-12.2013     Document Type: Article

References (91)

1. Adams MM, Fink SE, Shah RA, Janssen WG, Hayashi S, Milner TA, McEwen BS, Morrison JH (2002) Estrogen and aging affect the subcellular distribution of estrogen receptor-_ in the hippocampus of female rats. J Neurosci 22:3608-3614. Medline
2. Aenlle KK, Foster TC (2010) Aging alters the expression of genes for neuroprotection and synaptic function following acute estradiol treatment. Hippocampus 20:1047-1060. CrossRef Medline
3. Aenlle KK, Kumar A, Cui L, Jackson TC, Foster TC (2009) Estrogen effects on cognition and hippocampal transcription in middle-aged mice. Neurobiol Aging 30:932-945. CrossRef Medline
4. Akama KT, McEwen BS (2003) Estrogen stimulates postsynaptic density-95 rapid protein synthesis via the Akt/protein kinase B pathway. J Neurosci 23:2333-2339. Medline
5. Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J, Nilsson S (1998) Differential response of estrogen receptor α and estrogen receptor β to partial estrogen agonists/antagonists. Mol Pharmacol 54:105-112. Medline
6. Bimonte-Nelson HA, Francis KR, Umphlet CD, Granholm AC (2006) Progesterone reverses the spatial memory enhancements initiated by tonic and cyclic oestrogen therapy in middle-aged ovariectomized female rats. Eur J Neurosci 24:229-242. CrossRef Medline
7. Blalock EM, Chen KC, Sharrow K, Herman JP, Porter NM, Foster TC, Landfield PW (2003) Gene microarrays in hippocampal aging: statistical profiling identifies novel processes correlated with cognitive impairment. J Neurosci 23:3807-3819. Medline
8. Bohacek J, Daniel JM (2009) The ability of oestradiol administration to regulate protein levels of oestrogen receptor α in the hippocampus and prefrontal cortex of middle-aged rats is altered following long-term ovarian hormone deprivation. J Neuroendocrinol 21:640-647. CrossRef Medline
9. Choi JM, Romeo RD, Brake WG, Bethea CL, Rosenwaks Z, McEwen BS (2003) Estradiol increases pre- and post-synaptic proteins in the CA1 region of the hippocampus in female rhesus macaques (Macaca mulatta). Endocrinology 144:4734-4738. CrossRef Medline
10. Corbo RM, Gambina G, Ruggeri M, Scacchi R (2006) Association of estrogen receptor α (ESR1) PvuII and XbaI polymorphisms with sporadic Alzheimer's disease and their effect on apolipoprotein E concentrations. Dement Geriatr Cogn Disord 22:67-72. CrossRef Medline
11. Daniel JM, Hulst JL, Berbling JL (2006) 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 147:607-614. CrossRef Medline
12. Dubal DB, Rau SW, Shughrue PJ, Zhu H, Yu J, Cashion AB, Suzuki S, Gerhold LM, Bottner MB, Dubal SB, Merchanthaler I, Kindy MS, Wise PM (2006) Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERβ in estradiol-mediated protection against delayed cell death. Endocrinology 147:3076-3084. CrossRef Medline
13. Enmark E, Gustafsson JA (1999) Oestrogen receptors: an overview. J Intern Med 246:133-138. CrossRef Medline
14. Fan X, Gabbi C, Kim HJ, Cheng G, Andersson LC, Warner M, Gustafsson JA (2010) Gonadotropin-positive pituitary tumors accompanied by ovarian tumors in aging female ER α/β mice. Proc Natl Acad Sci U S A 107:6453-6458. CrossRef Medline
15. Foster TC (2005) Interaction of rapid signal transduction cascades and gene expression in mediating estrogen effects on memory over the life span. Front Neuroendocrinol 26:51-64. CrossRef Medline
16. Foster TC (2012) Role of estrogen receptor α and β expression and signaling on cognitive function during aging. Hippocampus 22:656-669. CrossRef Medline
17. Foster TC, Sharrow KM, Kumar A, Masse J (2003) Interaction of age and chronic estradiol replacement on memory and markers of brain aging. Neurobiol Aging 24:839-852. CrossRef Medline
18. Foster TC, Rani A, Kumar A, Cui L, Semple-Rowland SL (2008) Viral vector-mediated delivery of estrogen receptor- to the hippocampus improves spatial learning in estrogen receptor knock-out mice. Mol Ther 16:1587-1593. CrossRef Medline
19. Frick KM, Fernandez SM, Bulinski SC (2002) Estrogen replacement improves spatial reference memory and increases hippocampal synaptophysin in aged female mice. Neuroscience 115:547-558. CrossRef Medline
20. Fugger HN, Cunningham SG, Rissman EF, Foster TC (1998) Sex differences in the activational effect of ERβ on spatial learning. Horm Behav 34:163-170. CrossRef Medline
21. Fugger HN, Foster TC, Gustafsson J, Rissman EF (2000) Novel effects of estradiol and estrogen receptor α and β on cognitive function. Brain Res 883:258-264. CrossRef Medline
22. Garcia-Segura LM, Sanz A, Mendez P (2006) Cross-talk between IGF-I and estradiol in the brain: focus on neuroprotection. Neuroendocrinology 84:275-279. CrossRef Medline
23. Gibbs RB (2000) Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats. Neurobiol Aging 21:107-116. CrossRef Medline
24. Gonzales KL, Tetel MJ, Wagner CK (2008) Estrogen receptor (ER) α modulates ERβ responses to estrogens in the developing rat ventromedial nucleus of the hypothalamus. Endocrinology 149:4615-4621. CrossRef Medline
25. Gordon MN, Osterburg HH, May PC, Finch CE (1986) Effective oral administration of 17 α-estradiol to female C57BL/6J mice through the drinking water. Biol Reprod 35:1088-1095. CrossRef Medline
26. Gottfried-Blackmore A, Croft G, McEwen BS, Bulloch K (2007) Transcriptional activity of estrogen receptors ERα and ERβ in the EtC. 1 cerebellar granule cell line. Brain Res 1186:41-47. CrossRef Medline
27. Gould E, Woolley CS, Frankfurt M, McEwen BS (1990) Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci 10:1286-1291.Medline
28. Gresack JE, Frick KM (2006) Effects of continuous and intermittent estrogen treatments on memory in aging female mice. Brain Res 1115:135-147. CrossRef Medline
29. Hall JM, McDonnell DP (1999) The estrogen receptor αisoform (ERα) of the human estrogen receptor modulates ER α transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology 140:5566-5578. CrossRef Medline
30. Hammer RE, Idzerda RL, Brinster RL, McKnight GS (1986) Estrogen regulation of the avian transferrin gene in transgenic mice. Mol Cell Biol 6:1010-1014. CrossRef Medline
31. Harrington WR, Sheng S, Barnett DH, Petz LN, Katzenellenbogen JA, Katzenellenbogen BS (2003) Activities of estrogen receptor and α-selective ligands at diverse estrogen responsive gene sites mediating transactivation or transrepression. Mol Cell Endocrinol 206:13-22.CrossRef Medline
32. Hong-Goka BC, Chang FL (2004) Estrogen receptors α and βin choroids plexus epithelial cells in Alzheimer's disease. Neurosci Lett 360:113-116.CrossRef Medline
33. Iivonen S, Heikkinen T, Puoliväli J, Helisalmi S, Hiltunen M, Soininen H, Tanila H (2006) Effects of estradiol on spatial learning, hippocampal cytochrome P450 19, and estrogen α and β mRNA levels in ovariectomized female mice. Neuroscience 137:1143-1152. CrossRef Medline
34. Ishunina TA, Fischer DF, Swaab DF (2007) Estrogen receptor α and its splice variants in the hippocampus in aging and Alzheimer's disease. Neurobiol Aging 28:1670-1681. CrossRef Medline
35. Jelks KB, Wylie R, Floyd CL, McAllister AK, Wise P (2007) Estradiol targets synaptic proteins to induce glutamatergic synapse formation in cultured hippocampal neurons: critical role of estrogen receptor-α. J Neurosci 27:6903-6913. CrossRef Medline
36. Ji Y, Urakami K, Wada-Isoe K, Adachi Y, Nakashima K (2000) Estrogen receptor gene polymorphisms in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia. Dement Geriatr Cogn Disord 11:119-122. CrossRef Medline
37. Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu X, Li M, Sousa AM, Pletikos M, Meyer KA, Sedmak G, Guennel T, Shin Y, Johnson MB, Krsnik Z, Mayer S, Fertuzinhos S, Umlauf S, Lisgo SN, Vortmeyer A, Weinberger DR, et al. (2011) Spatio-temporal transcriptome of the human brain. Nature 478: 483-489. CrossRef Medline
38. Karmakar S, Foster EA, Smith CL (2009) Estradiol downregulation of the tumor suppressor gene BTG2 requires estrogen receptor-β and the REA corepressor. Int J Cancer 124:1841-1851. CrossRef Medline
39. Katzenellenbogen BS, Korach KS (1997) A new actor in the estrogen receptor drama: enter ER-β. Endocrinology 138:861-862. CrossRef Medline
40. Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, Sar M, Korach KS, Gustafsson JA, Smithies O (1998) Generation and reproductive phenotypes of mice lacking estrogen receptor α. Proc Natl Acad Sci U S A 95:15677-15682. CrossRef Medline
41. Kretz O, Fester L, Wehrenberg U, Zhou L, Brauckmann S, Zhao S, Prange-Kiel J, Naumann T, Jarry H, Frotscher M, Rune GM (2004) Hippocampal synapses depend on hippocampal estrogen synthesis. J Neurosci 24: 5913-5921. CrossRef Medline
42. Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology 138:863-870. CrossRef Medline
43. Lee WH, Kumar A, Rani A, Herrera J, Xu J, Someya S, Foster TC (2012) Influence of viral vector-mediated delivery of superoxide dismutase and catalase to the hippocampus on spatial learning and memory during aging. Antioxid Redox Signal 16:339-350. CrossRef Medline
44. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ, Chen L, Chen L, Chen TM, Chin MC, Chong J, Crook BE, Czaplinska A, Dang CN, Datta S, Dee NR, et al. (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445:168-176. CrossRef Medline
45. Li J, Wong L (2001) Emerging patterns and gene expression data. Genome Inform 12:3-13. Medline
46. Li C, Brake WG, Romeo RD, Dunlop JC, Gordon M, Buzescu R, Magarinos AM, Allen PB, Greengard P, Luine V, McEwen BS (2004) Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice. Proc Natl Acad SciU S A 101:2185-2190. CrossRef Medline
47. Lin Y, Bloodgood BL, Hauser JL, Lapan AD, Koon AC, Kim TK, Hu LS, Malik AN, Greenberg ME (2008) Activity-dependent regulation of inhibitory synapse development by Npas4. Nature 455:1198-1204. CrossRef Medline
48. Lindberg MK, Weihua Z, Andersson N, Movérare S, Gao H, Vidal O, Erlandsson M, Windahl S, Andersson G, Lubahn DB, Carlsten H, Dahlman-Wright K, Gustafsson JA, Ohlsson C (2002) Estrogen receptor specificity for the effects of estrogen in ovariectomized mice. J Endocrinol 174:167-178. CrossRef Medline
49. Lindberg MK, Moverare S, Skrtic S, Gao H, Dahlman-Wright K, Gustafsson JA, Ohlsson C (2003) Estrogen receptor (ER)-β reduces ERα-regulated gene transcription, supporting a "ying yang" relationship between ER β and ERv in mice. Mol Endocrinol (Baltimore) 17:203-208. CrossRef Medline
50. Liu F, Day M, Muniz LC, Bitran D, Arias R, Revilla-Sanchez R, Grauer S, Zhang G, Kelley C, Pulito V, Sung A, Mervis RF, Navarra R, Hirst WD, Reinhart PH, Marquis KL, Moss SJ, Pangalos MN, Brandon NJ (2008) Activation of estrogen receptor-β regulates hippocampal synaptic plasticity and improves memory. Nat Neurosci 11:334-343. CrossRef Medline
51. Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O (1993) Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci U S A 90:11162-11166. CrossRef Medline
52. Markham JA, Pych JC, Juraska JM (2002) Ovarian hormone replacement to aged ovariectomized female rats benefits acquisition of the Morris water maze. Horm Behav 42:284-293. CrossRef Medline
53. Markowska AL, Savonenko AV (2002) Effectiveness of estrogen replacement in restoration of cognitive function after long-term estrogen withdrawal in aging rats. J Neurosci 22:10985-10995. Medline
54. Mehra RD, Sharma K, Nyakas C, Vij U (2005) Estrogen receptor α and β immunoreactive neurons in normal adult and aged female rat hippocampus: a qualitative and quantitative study. Brain Res 1056:22-35. CrossRef Medline
55. Nilsen J, Diaz Brinton R (2003) Mechanism of estrogen-mediated neuroprotection: regulation of mitochondrial calcium and Bcl-2 expression. Proc Natl Acad Sci U S A 100:2842-2847. CrossRef Medline
56. Nilsson S, Mäkelä S, Treuter E, Tujague M, Thomsen J, Andersson G, Enmark E, Pettersson K, Warner M, Gustafsson JA (2001) Mechanisms of estrogen action. Physiol Rev 81:1535-1565. Medline
57. Noppens RR, Kofler J, Hurn PD, Traystman RJ (2005) Dose-dependent neuroprotection by 17α-estradiol after cardiac arrest and cardiopulmonary resuscitation. Crit Care Med 33:1595-1602. CrossRef Medline
58. O'Lone R, Knorr K, Jaffe IZ, Schaffer ME, Martini PG, Karas RH, Bienkowska J, Mendelsohn ME, Hansen U (2007) Estrogen receptors α and βmediate distinct pathways of vascular gene expression, including genes involved in mitochondrial electron transport and generation of reactive oxygen species. Mol Endocrinol (Baltimore) 21:1281-1296. CrossRefMedline
59. Olsen L, Rasmussen HB, Hansen T, Bagger YZ, Tanko ́ LB, Qin G, Christiansen C, Werge T (2006) Estrogen receptor α and risk for cognitive impairment in postmenopausal women. Psychiatr Genet 16:85-88.CrossRef Medline
60. Paruthiyil S, Cvoro A, Tagliaferri M, Cohen I, Shtivelman E, Leitman DC (2011) Estrogen receptor β causes a G2 cell cycle arrest by inhibiting CDK1 activity through the regulation of cyclin B1, GADD45A, and BTG2. Breast Cancer Res Treat. 129:777-784. CrossRef Medline
61. Pettersson K, Delaunay F, Gustafsson JA (2000) Estrogen receptor β acts as a dominant regulator of estrogen signaling. Oncogene 19:4970-4978. CrossRef Medline
62. Prange-Kiel J, Wehrenberg U, Jarry H, Rune GM (2003) Para/autocrine regulation of estrogen receptors in hippocampal neurons. Hippocampus 13:226-234. CrossRef Medline
63. Priest CA, Eckersell CB, Micevych PE (1995) Estrogen regulates preproenkephalin-A mRNA levels in the rat ventromedial nucleus: temporal and cellular aspects. Brain Res Mol Brain Res 28:251-262. CrossRef Medline
64. Quintela T, Gonçalves I, Baltazar G, Alves CH, Saraiva MJ, Santos CR (2009) 17α-Estradiol induces transthyretin expression in murine choroid plexus via an oestrogen receptor dependent pathway. Cell Mol Neurobiol 29: 475-483. CrossRef Medline
65. Rissman EF, Heck AL, Leonard JE, Shupnik MA, Gustafsson JA (2002) Disruption of estrogen receptor β gene impairs spatial learning in female mice. Proc Natl Acad Sci U S A 99:3996-4001. CrossRef Medline
66. Rune GM, Frotscher M (2005) Neurosteroid synthesis in the hippocampus: role in synaptic plasticity. Neuroscience 136:833-842. CrossRef Medline
67. Semple-Rowland SL, Eccles KS, Humberstone EJ (2007) Targeted expression of two proteins in neural retina using self-inactivating, insulated lentiviral vectors carrying two internal independent promoters. Mol Vis 13:2001-2011.Medline
68. Sharma PK, Thakur MK (2006) Expression of estrogen receptor (ER) α and β in mouse cerebral cortex: effect of age, sex and gonadal steroids. Neurobiol Aging 27:880-887. CrossRef Medline
69. Sherwin BB (2006) Estrogen and cognitive aging in women. Neuroscience 138:1021-1026. CrossRef Medline
70. Shim GJ, Wang L, Andersson S, Nagy N, Kis LL, Zhang Q, Mäkelä S, Warner M, Gustafsson JA (2003) Disruption of the estrogen receptor β gene in mice causes myeloproliferative disease resembling chronic myeloid leukemia with lymphoid blast crisis. Proc Natl Acad Sci U S A 100:6694-6699. CrossRef Medline
71. Sohrabji F, Miranda RC, Toran-Allerand CD (1994) Estrogen differentially regulates estrogen and nerve growth factor receptor mRNAs in adult sensory neurons. J Neurosci 14:459-471. Medline
72. Sohrabji F, Miranda RC, Toran-Allerand CD (1995) Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor. Proc Natl Acad Sci U S A 92:11110-11114. CrossRef Medline
73. Talboom JS, Williams BJ, Baxley ER, West SG, Bimonte-Nelson HA (2008) Higher levels of estradiol replacement correlate with better spatial memory in surgically menopausal young and middle-aged rats. Neurobiol Learn Mem 90:155-163. CrossRef Medline
74. Tang YP, Haslam SZ, Conrad SE, Sisk CL (2004) Estrogen increases brain expression of the mRNA encoding transthyretin, an amyloid β scavenger protein. J Alzheimers Dis 6; 443-449. Medline
75. Thakur MK, Sharma PK (2007) Transcription of estrogen receptor α and β in mouse cerebral cortex: effect of age, sex, 17 β-estradiol and testosterone. Neurochem Int 50:314-321. CrossRef Medline
76. Tohgi H, Utsugisawa K, Yamagata M, Yoshimura M (1995) Effects of age on messenger RNA expression of glucocorticoid, thyroid hormone, androgen, and estrogen receptors in postmortem human hippocampus. Brain Res 700:245-253. CrossRef Medline
77. Too CK, Giles A, Wilkinson M (1999) Estrogen stimulates expression of adenine nucleotide translocator ANT1 messenger RNA in female rat hearts. Mol Cell Endocrinol 150:161-167. CrossRef Medline
78. Tremblay GB, Tremblay A, Copeland NG, Gilbert DJ, Jenkins NA, Labrie F, Giguere V (1997) Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor α. Mol Endocrinol (Baltimore) 11:353-365. CrossRef Medline
79. Walf AA, Koonce CJ, Frye CA (2008) Estradiol or diarylpropionitrile administration to wild type, but not estrogen receptor α knockout, mice enhances performance in the object recognition and object placement tasks. Neurobiol Learn Mem 89:513-521. CrossRef Medline
80. Walf AA, Koonce C, Manley K, Frye CA (2009) Proestrous compared with diestrous wild-type, but not estrogen receptor α knockout, mice have better performance in the spontaneous alternation and object recognition tasks and reduced anxiety-like behavior in the elevated plus and mirror maze. Behav Brain Res 196:254-260. CrossRef Medline
81. Wang L, Andersson S, Warner M, Gustafsson JA (2001) Morphological abnormalities in the brains of estrogen receptor β knockout mice. Proc Natl Acad Sci U S A 98:2792-2796. CrossRef Medline
82. Williams C, Edvardsson K, Lewandowski SA, Strom A, Gustafsson JA (2008) A genome-wide study of the repressive effects of estrogen receptor β on estrogen receptor α signaling in breast cancer cells. Oncogene 27:1019-1032. CrossRef Medline
83. _/_ mice are partially protected against age-related trabecular bone loss. J Bone Miner Res 16:1388-1398. CrossRef Medline
84. Woo JM, Park SJ, Kang HI, Kim BG, Shim SB, Jee SW, Lee SH, Sin JS, Bae CJ, Jang MK, Cho C, Hwang DY, Kim CK (2010) Characterization of changes in global gene expression in the brain of neuron-specific enolase/human Tau23 transgenic mice in response to overexpression of Tau protein. Int J Mol Med 25:667-675. CrossRef Medline
85. Woolley CS, McEwen BS (1992) Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J Neurosci 12:2549-2554.Medline
86. Woolley CS, McEwen BS (1993) Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol 336:293-306. CrossRef Medline
87. Woolley CS, Gould E, Frankfurt M, McEwen BS (1990) Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J Neurosci 10:4035-4039. Medline
88. Xu X, Zhang Z (2006) Effects of estradiol benzoate on learning-memory behavior and synaptic structure in ovariectomized mice. Life Sci 79:1553-1560. CrossRef Medline
89. Yaffe K, Lindquist K, Sen S, Cauley J, Ferrell R, Penninx B, Harris T, Li R, Cummings SR (2009) Estrogen receptor genotype and risk of cognitive impairment in elders: findings from the Health ABC study. Neurobiol Aging 30:607-614. CrossRef Medline
90. Yang SH, Sarkar SN, Liu R, Perez EJ, Wang X, Wen Y, Yan LJ, Simpkins JW (2009) Estrogen receptor β as a mitochondrial vulnerability factor. J Biol Chem 284:9540-9548. CrossRef Medline
91. Zeier Z, Kumar A, Bodhinathan K, Feller JA, Foster TC, Bloom DC (2009) Fragile X mental retardation protein replacement restores hippocampal synaptic function in a mouse model of fragile X syndrome. Gene Ther 16:1122-1129. CrossRef Medline