Glutamate presynaptic vesicular transporter and postsynaptic receptor levels correlate with spatial memory status in aging rat models

Abstract

In humans, memory capacities are generally affected with aging, even without any reported neurologic disorders. The mechanisms behind cognitive decline are not well understood. We studied here whether postsynaptic glutamate receptor and presynaptic vesicular glutamate transporters (VGLUTs) levels may change in the course of aging and be related to cognitive abilities using various age-impaired (AI) or age-unimpaired rat strains. Twenty-four-month-old Long-Evans (LE) rats with intact spatial memory maintained postsynaptic ionotropic glutamate receptor levels in the hippocampal-adjacent cortex similar to those of young animals. In contrast, AI rats showed significantly reduced expression of ionotropic glutamate receptor GluR2, NR2A and NR2B subunits. In AI LE rats, VGLUT1 and VGLUT2 levels were increased and negatively correlated with receptor levels as shown by principal component analysis and correlation matrices. We also investigated whether glutamatergic receptors and VGLUT levels were altered in the obesity-resistant LOU/C/Jall (LOU) rat strain which is characterized by intact memory despite aging. No difference was observed between 24-month-old LOU rats and their young counterparts. Taken together, the unaltered spatial memory performance of 24-month-old age-unimpaired LE and LOU rats suggests that intact coordination of the presynaptic and postsynaptic hippocampal-adjacent cortex glutamatergic networks may be important for successful cognitive aging. Accordingly, altered expression of presynaptic and postsynaptic glutamatergic components, such as in AI LE rats, could be considered a marker of age-related cognitive deficits.

Sex Differences in Psychiatric Disease: A Focus on the Glutamate System

“…Although there were no sex differences in the total glutamate concentrations, the authors report a significant interaction between age and brain region in the ratio of glutamine/glutamate, which may reflect differences in glutamatergic transmission between neurons and glial cells (Duarte et al, 2014 ). Decreased levels of GluA1, GluN2A, and GluN2B glutamate receptor subunit levels over the course of aging (6 mo vs. 24 mos) have been correlated with poorer cognitive performance in male rats, but these studies have not been done in females (Ménard et al, 2015 ).…”

A complement–microglial axis drives synapse loss during virus-induced memory impairment

“…3a). Altered expression of the presynaptic glutamatergic vesicular transporter, VGlut1 (also known as Slc17a7), in the hippocampus has been linked to cognitive impairment in rodents 22 . Evidence of hippocampal glutamatergic synapse loss was detectable at 25 dpi and WNV-NS5-E218A-recovered mice with poor spatial learning exhibited fewer VGlut1-positive synaptic puncta than WNV-NS5-E218A-infected good learners, which were fewer than in mock-infected controls (Fig.…”

FK506-Binding Protein 12.6/1b, a Negative Regulator of [Ca2+], Rescues Memory and Restores Genomic Regulation in the Hippocampus of Aging Rats

“…An interesting question not addressed here is whether animals already performing at a high baseline, including young animals and the small percentage of aged animals that are unimpaired ( Bäckman et al, 1996 ; Gallagher and Rapp, 1997 ; Tombaugh et al, 2002 ; Rowe et al, 2003 , 2007 ; Curlik et al, 2014 ; Ménard et al, 2015 ), show improved memory with FKBP1b . It will be important in future studies to determine whether unimpaired animals are resistant or sensitive to the actions of FKBP1b on memory.…”