Pharmacological regulation of voltage-gated calcium channels in basal forebrain neurons from behaviorally characterized young, middle and aged rats : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
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College Station, Tex. :
Texas A&M University System Health Science Center,
2008.
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| Subjects: |
| Abstract: | ABSTRACT: The aging process is often associated with cognitive decline and organ system deterioration. In an effort to understand what may predispose some patients to these age-related changes, we used an animal model of normal aging, behavioral characterization of subjects and electrophysiological methods to test the hypothesis that decline in the function of cholinergic neuron and calcium signaling underlie the cognitive changes experienced during aging. Specifically, we studied whole-cell calcium current in cholinergic neurons of the basal forebrain (BF) across aging and cognitive status. We found that high- and low- voltage activated calcium (HVA and LVA) current density did not change with age or cognitive staus. However, because elderly patients are at an increased risk for developing depressive symptoms, we investigated potential age-related changes of antidepressant effects on BF whole cell calcium currents from behaviorally characterized animals. We tested four different antidepressants and found that each drug inhibited HVA calcium currents in a concentration-dependent manner. The concentrations for half-maximal inhibition were 98.02 [micromolar]M for amitriptyline, 37.2 [micromolar]M for fluoxetine, 265.71 [micromolar]M for citalopram and 54.62 [micromolar]M for bupropion. Amitriptyline (100 [micromolar]M) was used to test calcium current inhibition across aging and cognitive status. Amitriptyline significantly inhibited more calcium current in aged (A) animals (mean [plus minus] SEM for young (Y) 47.31 [plus minus] 3.47%, 50.34 [plus minus] 5.47% in middle-aged (M) and 64.55 [plus minus] 4.36% inhibition in A animals. When the cognitive status of the animal was considered, we found that amitriptyline inhibited significantly more current in the aged unimpaired (AU) animals. Current inhibition by amitriptyline was 47.31 [plus minus] 3.47% in Y animals, 48.19 [plus minus] 6.24% in M unimpaired animals, 56.25 [plus minus] 12.27% in M impaired animals. 74.74 [plus minus] 4.90% in AU animals and 55.50 [plus minus] 5.60% in A impaired animals. Finally the functional consequences HVA inhibition was investigated by testing the effects of amitriptyline on synaptic treansmission in the BF. Amitriptyline (100 [micromolar]M) modulated neurotransmitter release by increasing the release probability at some synapses. All of our results demonstrate a remarkable plasticity of calcium signaling in the BF across aging and cognitive status. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Office of Research and Graduate Studies of The Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy August 2008." Approved as to style and content by: William H. Griffith, III, Gerald D. Frye, Farida Sohrabji, Jennifer L. Bizon, William H. Griffith, III |
| Physical Description: | xi, 181 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 126-179). |