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

Neurobiol Aging. 2015 Mar;36(3):1471-82. doi: 10.1016/j.neurobiolaging.2014.11.013. Epub 2014 Nov 26.


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.

Keywords: AMPA; Aging; Glutamate receptors; NMDA; Spatial memory; VGLUT; mGluR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / psychology*
  • Animals
  • Biomarkers / metabolism
  • Cerebral Cortex / metabolism
  • Cognition Disorders / diagnosis
  • Female
  • Gene Expression / genetics*
  • Hippocampus / metabolism
  • Male
  • Models, Animal
  • Rats, Inbred Strains
  • Rats, Long-Evans
  • Receptors, AMPA / genetics*
  • Receptors, AMPA / metabolism*
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Spatial Memory / physiology*
  • Vesicular Glutamate Transport Protein 1 / genetics*
  • Vesicular Glutamate Transport Protein 1 / metabolism*
  • Vesicular Glutamate Transport Protein 2 / genetics*
  • Vesicular Glutamate Transport Protein 2 / metabolism*


  • Biomarkers
  • NR2A NMDA receptor
  • NR2B NMDA receptor
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Slc17a6 protein, rat
  • Slc17a7 protein, rat
  • Vesicular Glutamate Transport Protein 1
  • Vesicular Glutamate Transport Protein 2
  • glutamate receptor ionotropic, AMPA 2