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Research Paper|Volume 16, Issue 10|pp 8402—8416

Serine racemase expression profile in the prefrontal cortex and hippocampal subregions during aging in male and female rats

Linda Bean1, Prodip K. Bose2,3, Asha Rani4, Ashok Kumar4
  • 1Department of Anatomy, Cell Biology, and Physiology, IU School of Medicine, Indianapolis, IN 46201, USA
  • 2Brain Rehabilitation Research Center, Malcom Randall Department of Veterans Affairs Medical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL 32607, USA
  • 3Department of Anesthesiology and Department of Neurology at the College of Medicine, University of Florida, FL 32607, USA
  • 4Department of Neuroscience, The McKnight Brain Institute, University of Florida, Gainesville, FL 32607, USA
Received: December 27, 2023Accepted: April 10, 2024Published: May 17, 2024
https://doi.org/10.18632/aging.205841

Copyright: © 2024 Bean et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aging is associated with a decrease in N-methyl-D-aspartate (NMDA) receptor function, which is critical for maintaining synaptic plasticity, learning, and memory. Activation of the NMDA receptor requires binding of the neurotransmitter glutamate and also the presence of co-agonist D-serine at the glycine site. The enzymatic conversion of L-serine to D-serine is facilitated by the enzyme serine racemase (SR). Subsequently, SR plays a pivotal role in regulating NMDA receptor activity, thereby impacting synaptic plasticity and memory processes in the central nervous system. As such, age-related changes in the expression of SR could contribute to decreased NMDA receptor function. However, age-associated changes in SR expression levels in the medial and lateral prefrontal cortex (mPFC, lPFC), and in the dorsal hippocampal subfields, CA1, CA3, and dentate gyrus (DG), have not been thoroughly elucidated. Therefore, the current studies were designed to determine the SR expression profile, including protein levels and mRNA, for these regions in aged and young male and female Fischer-344 rats. Our results demonstrate a significant reduction in SR expression levels in the mPFC and all hippocampal subfields of aged rats compared to young rats. No sex differences were observed in the expression of SR. These findings suggest that the decrease in SR levels may play a role in the age-associated reduction of NMDA receptor function in brain regions crucial for cognitive function and synaptic plasticity.