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Serine Racemase Expression Profile in the Prefrontal Cortex and Hippocampal Subregions During Aging in Male and Female Rats

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Specialty Geriatrics
Date 2024 May 18
PMID 38761177
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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.

References
1.
Potier B, Turpin F, Sinet P, Rouaud E, Mothet J, Videau C . Contribution of the d-Serine-Dependent Pathway to the Cellular Mechanisms Underlying Cognitive Aging. Front Aging Neurosci. 2010; 2:1. PMC: 2874399. DOI: 10.3389/neuro.24.001.2010. View

2.
Williams S, Diaz C, Macnab L, Sullivan R, Pow D . Immunocytochemical analysis of D-serine distribution in the mammalian brain reveals novel anatomical compartmentalizations in glia and neurons. Glia. 2005; 53(4):401-11. DOI: 10.1002/glia.20300. View

3.
Kumar A, Foster T . Linking redox regulation of NMDAR synaptic function to cognitive decline during aging. J Neurosci. 2013; 33(40):15710-5. PMC: 3787496. DOI: 10.1523/JNEUROSCI.2176-13.2013. View

4.
Billard J, Rouaud E . Deficit of NMDA receptor activation in CA1 hippocampal area of aged rats is rescued by D-cycloserine. Eur J Neurosci. 2007; 25(8):2260-8. DOI: 10.1111/j.1460-9568.2007.05488.x. View

5.
Wu S, Barger S . Induction of serine racemase by inflammatory stimuli is dependent on AP-1. Ann N Y Acad Sci. 2005; 1035:133-46. DOI: 10.1196/annals.1332.009. View