Estrogen replacement therapy in elderly women has been reported to diminish the risk of developing Alzheimer's disease (AD) and to improve response to anti-cholinesterase therapy in women already diagnosed with AD. Further, recent evidence indicates that estrogen may modulate the expression of neuronal growth factors and their receptors in the brain. These findings suggest that neuronal plasticity in the brain may be modulated in part by estrogen-linked mechanisms. To investigate this possibility, our laboratory has explored interactions of estrogen-responsive neurons with growth factors and their receptors. We have found extensive co-expression of estrogen and neurotrophin systems in both cortical regions and forebrain projections to cortical regions in the brains of rodents and primates. Studies in this proposal will examine the effects of neuronal injury and estrogen loss on neural plasticity to test the hypothesis that estrogens modulate neural plasticity to test the hypothesis that estrogens modulate neural plasticity through interactions with neurotrophic factor systems in the brain. Mechanisms of such interactions will be elucidated. This work will build upon techniques and methods that are will-established in the PI's lab and that have led to useful insights into the nature of neurotrophin biology in the rodent and primate brains.
The specific aims will be addressed:
Aim 1 : Do neuronal populations in the primate and rodent brains co-express estrogen receptors and neurotrophins or their receptors, reflecting co- modulation of these systems? Aim 2: What effects do natural fluctuations in estrogen levels exert on cortical synapse density and on expression of NGF, BDNF and neurotrophin receptors in the brain? Aims 3 and 4: What effect does estrogen loss exert on synapse density in cortical target regions, and on expression of neurotrophins and their receptors, in the brains of adult and aged rats (Aim 3) and in the brains of adult primates (Aim 4)? Aim 5: Do estrogens and growth factors act synergistically to enhance neural plasticity? These studies will provide insights regarding estrogen effects on going, cognition, and neurotrophic factors, leading to potential novel therapeutic approaches to AD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
3P50AG005131-16S3
Application #
6395446
Study Section
Project Start
1999-08-15
Project End
2000-03-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
16
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Hadjichrysanthou, Christoforos; McRae-McKee, Kevin; Evans, Stephanie et al. (2018) Potential Factors Associated with Cognitive Improvement of Individuals Diagnosed with Mild Cognitive Impairment or Dementia in Longitudinal Studies. J Alzheimers Dis 66:587-600
Chen, Xu-Qiao; Fang, Fang; Florio, Jazmin B et al. (2018) T-complex protein 1-ring complex enhances retrograde axonal transport by modulating tau phosphorylation. Traffic 19:840-853
Hanfelt, John J; Peng, Limin; Goldstein, Felicia C et al. (2018) Latent classes of mild cognitive impairment are associated with clinical outcomes and neuropathology: Analysis of data from the National Alzheimer's Coordinating Center. Neurobiol Dis 117:62-71
Zhou, Zilu; Wang, Weixin; Wang, Li-San et al. (2018) Integrative DNA copy number detection and genotyping from sequencing and array-based platforms. Bioinformatics 34:2349-2355
Burke, Shanna L; Hu, Tianyan; Fava, Nicole M et al. (2018) Sex differences in the development of mild cognitive impairment and probable Alzheimer's disease as predicted by hippocampal volume or white matter hyperintensities. J Women Aging :1-25
Wang, Qi; Guo, Lei; Thompson, Paul M et al. (2018) The Added Value of Diffusion-Weighted MRI-Derived Structural Connectome in Evaluating Mild Cognitive Impairment: A Multi-Cohort Validation1. J Alzheimers Dis 64:149-169
Sundermann, Erin E; Tran, My; Maki, Pauline M et al. (2018) Sex differences in the association between apolipoprotein E ?4 allele and Alzheimer's disease markers. Alzheimers Dement (Amst) 10:438-447
Besser, Lilah; Kukull, Walter; Knopman, David S et al. (2018) Version 3 of the National Alzheimer's Coordinating Center's Uniform Data Set. Alzheimer Dis Assoc Disord 32:351-358
Graves, Lisa V; Van Etten, Emily J; Holden, Heather M et al. (2018) Refining CVLT-II recognition discriminability indices to enhance the characterization of recognition memory changes in healthy aging. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 25:767-782
Edmonds, Emily C; Weigand, Alexandra J; Thomas, Kelsey R et al. (2018) Increasing Inaccuracy of Self-Reported Subjective Cognitive Complaints Over 24 Months in Empirically Derived Subtypes of Mild Cognitive Impairment. J Int Neuropsychol Soc 24:842-853

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