Glutamate receptor plasticity in the hippocampus: Implications for age-related memory and learning deficits.
Item
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Title
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Glutamate receptor plasticity in the hippocampus: Implications for age-related memory and learning deficits.
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Identifier
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AAI9720091
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identifier
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9720091
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Creator
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Gazzaley, Adam H.
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Contributor
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Adviser: John H. Morrison
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Date
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1997
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience | Biology, Cell
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Abstract
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Memory and learning deficits that negatively impact on quality of life are a common occurrence in our aged population. The studies described in this thesis were designed to further our understanding of cellular and molecular alterations occurring in conditions that are associated with age-related memory and learning deficits. Based on the established importance of glutamate receptors and the hippocampus in memory and learning processes, we first investigated potential differences in glutamate receptor immunofluorescence within the hippocampus of juvenile, adult, and aged macaque monkeys. Second, to explore the influence of fluctuations in estrogen levels, comparable to those that occur during menopause, on NMDARs, we compared both NMDAR1 immunofluorescence and mRNA in situ hybridization intensity within different hippocampal regions between ovariectomized rats and ovariectomized rats treated with estradiol and progesterone. Third, to investigate the effects of altering a key afferent input on NMDARs, which we hypothesize occurs to some degree during aging, we evaluated NMDAR1 immunofluorescence and mRNA in situ hybridization intensity in rat dentate gyrus following synaptic reorganization induced by unilateral transection of the perforant path input from the entorhinal cortex. The results of these studies reveal that glutamate receptor plasticity is associated with all three conditions. In the first study, we demonstrated a circuit-specific decrease in NMDAR1 immunofluorescence within the dendrites of the dentate gyrus. The second study revealed that estrogen serves to maintain NMDAR1 immunofluorescence intensity levels within both the dentate gyrus and the CA1 field of the hippocampus, possibly via post-transcriptional regulation of the NMDAR1 subunit protein. Lastly, the third study demonstrated that both NMDAR1 protein and mRNA levels are modifiable by changes in afferent input, and additionally demonstrated that NMDAR1 mRNA is one of a limited population of mRNAs that is transported into dendrites. In conclusion, the data presented in this thesis suggest that alterations in the distribution of NMDAR1 protein, which may have been precipitated by fluctuations in estrogen levels and an alteration in afferent input, occurs in the hippocampus during aging and may be associated with age-related memory and learning impairment.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
