Recent evidence indicates that estrogen treatment in ovariectomized rats enhances performance on memory tasks. Similarly, human observations suggest a beneficial effect of estrogen treatment on cognitive function in Alzheimer's disease. However, those cellular targets of gonadal hormones that are directly involved in memory processes are ill defined. The only solid observations are that systemic hormonal manipulations result in changes in the density of spines and alterations in the intensity of immunostaining for NMDA receptor of hippocampal CAl pyramidal cells. However, hippocampal principal neurons themselves do not, only a small population of interneurons contains nuclear estrogen receptor. On the other hand, neurons in subcortical areas, including the medial septum diagonal band of Broca (MSDB), supramammillary area (SUM), and median raphe (MR) contain nuclear estrogen receptors, and these structures are associated with the generation/regulation of hippocampal theta activity and long term potentiation. Furthermore, hippocampal theta activity, which is greatly influenced by the changing levels of circulating estrogen, in conjunction with long-term potentiation is believed to be involved in memory processes. Therefore, the hypothesis that estrogen, in addition to influencing the hippocampus directly, regulates mnemonic processes by affecting these subcortical areas will be tested by experiments designed to examine the effects of intra-MR, -MSDB, and -SUM administration of estrogen in ovariectomized rats on: 1) changes in dendritic spine density of hippocampal CAl pyramidal cells; 2) mRNA and peptide levels of ionotropic glutamate receptors in the hippocampus; 3) hippocampal theta activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH060858-01A2
Application #
6331626
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (01))
Program Officer
Anderson, Kathleen C
Project Start
2001-04-06
Project End
2005-03-31
Budget Start
2001-04-06
Budget End
2002-03-31
Support Year
1
Fiscal Year
2001
Total Cost
$316,284
Indirect Cost
Name
Yale University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
MacLusky, Neil J; Thomas, Gladis; Leranth, Csaba (2017) Low dietary soy isoflavonoids increase hippocampal spine synapse density in ovariectomized rats. Brain Res 1657:361-367
Leranth, Csaba; Szigeti-Buck, Klara; Maclusky, Neil J et al. (2008) Bisphenol A prevents the synaptogenic response to testosterone in the brain of adult male rats. Endocrinology 149:988-94
Hajszan, Tibor; MacLusky, Neil J; Leranth, Csaba (2008) Role of androgens and the androgen receptor in remodeling of spine synapses in limbic brain areas. Horm Behav 53:638-46
Hajszan, Tibor; Milner, Teresa A; Leranth, Csaba (2007) Sex steroids and the dentate gyrus. Prog Brain Res 163:399-415
Leranth, Csaba; Hajszan, Tibor (2007) Extrinsic afferent systems to the dentate gyrus. Prog Brain Res 163:63-84
Hajszan, Tibor; MacLusky, Neil J; Johansen, Jamie A et al. (2007) Effects of androgens and estradiol on spine synapse formation in the prefrontal cortex of normal and testicular feminization mutant male rats. Endocrinology 148:1963-7
MacLusky, Neil J; Hajszan, Tibor; Johansen, Jamie A et al. (2006) Androgen effects on hippocampal CA1 spine synapse numbers are retained in Tfm male rats with defective androgen receptors. Endocrinology 147:2392-8
MacLusky, N J; Hajszan, T; Prange-Kiel, J et al. (2006) Androgen modulation of hippocampal synaptic plasticity. Neuroscience 138:957-65
MacLusky, Neil J; Luine, Victoria N; Hajszan, Tibor et al. (2005) The 17alpha and 17beta isomers of estradiol both induce rapid spine synapse formation in the CA1 hippocampal subfield of ovariectomized female rats. Endocrinology 146:287-93
MacLusky, Neil J; Hajszan, Tibor; Leranth, Csaba (2005) The environmental estrogen bisphenol a inhibits estradiol-induced hippocampal synaptogenesis. Environ Health Perspect 113:675-9

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