Age-related LTCC and NMDAR expression in the hippocampus and olfactory cortex in rats

Maziar, Aida (2022) Age-related LTCC and NMDAR expression in the hippocampus and olfactory cortex in rats. Masters thesis, Memorial University of Newfoundland.

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Abstract

Neuronal calcium is a critical mediator for learning and memory. However, with age, calcium dysregulation leads to cognitive decline. L-type calcium channels (LTCCs) and N-methyl-D-aspartate receptors (NMDARs) mediate Ca2+ influx in neurons. We hypothesized that there are age-related changes of calcium channel expression in the piriform cortex (PC) and hippocampus, two areas that are crucial for olfactory and spatial learning ability respectively. We measured synaptic and extrasynaptic levels of LTCCs (Cav1.2) and NMDAR subunits (GluN1, GluN2A, and GluN2B) in neonatal, adult, and aging rats using Western blot. PSD-95 colocalizing and non-colocalizing Cav1.2 expression were compared between adult and aging brains using immunohistochemistry and confocal microscopy, and we further investigated somatic and dendritic expression of both Cav1.2 and Cav1.3 subunits. The expression of hippocampal synaptic, but not extrasynaptic, NMDARs was higher in adult and aging groups compared to neonates. However, GluN2A/2B ratios and synaptic:extrasynaptic ratios of NMDAR subunits were similar across age groups. In contrast, in the PC, GluN2A/2B and synaptic:extrasynaptic ratios were higher in adult PC compared to neonates. In hippocampal CA1 and PC, the soma:dendritic ratio of Cav1.2 expression increased with aging, but the soma:dendritic ratio of Cav1.3 expression decreased. Extrasynaptic Cav1.2 non- PSD95 colocalizing expression was also found to have higher expression in the aging PC compared to adult. Our data suggest that PC and hippocampus are different in age-related channel expression. PC maturation is accompanied by a switch from GluN2B to GluN2A subunits. Higher somatic Cav1.2, but not Cav1.3 expression in CA1 and higher extrasynaptic Cav1.2 in the PC may correlate with aging-associated disruption of calcium homeostasis and cognitive decline.

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