Reduced serine racemase expression contributes to age-related deficits in hippocampal cognitive function

F.R. Turpin, B. Potier, J.R. Dulong, P.-M. Sinet, J. Alliot, S.H.R. Oliet, P. Dutar, J. Epelbaum, J.-P. Mothet, J.-M. Billard
Neurobiology of Aging. 2011-08-01; 32(8): 1495-1504
DOI: 10.1016/j.neurobiolaging.2009.09.001

PubMed
Lire sur PubMed



1. Neurobiol Aging. 2011 Aug;32(8):1495-504. doi:
10.1016/j.neurobiolaging.2009.09.001. Epub 2009 Oct 2.

Reduced serine racemase expression contributes to age-related deficits in
hippocampal cognitive function.

Turpin FR(1), Potier B, Dulong JR, Sinet PM, Alliot J, Oliet SH, Dutar P,
Epelbaum J, Mothet JP, Billard JM.

Author information:
(1)Centre de Psychiatrie et Neurosciences, INSERM, UMR 894, Université Paris
Descartes, Faculté de Médecine René Descartes, Paris, F-75014, France.

To gain insight into the contribution of d-serine to impaired cognitive aging, we
compared the metabolic pathway and content of the amino acid as well as
d-serine-dependent synaptic transmission and plasticity in the hippocampus of
young and old rats of the Wistar and Lou/C/Jall strains. Wistar rats display
cognitive impairments with aging that are not found in the latter strain, which
is therefore considered a model of healthy aging. Both mRNA and protein levels of
serine racemase, the d-serine synthesizing enzyme, were decreased in the
hippocampus but not in the cerebral cortex or cerebellum of aged Wistar rats,
whereas the expression of d-amino acid oxidase, which degrades the amino acid,
was not affected. Consequently, hippocampal levels of endogenous d-serine were
significantly lower. In contrast, serine racemase expression and d-serine levels
were not altered in the hippocampus of aged Lou/C/Jall rats. Ex vivo
electrophysiological recordings in hippocampal slices showed a marked reduction
in N-methyl-d-aspartate-receptor (NMDA-R)-mediated synaptic potentials and
theta-burst-induced long-term potentiation (LTP) in the CA1 area of aged Wistar
rats, which were restored by exogenous d-serine. In contrast, NMDA-R activation,
LTP induction and responses to d-serine were not altered in aged Lou/C/Jall rats.
These results further strengthen the notion that the serine racemase-dependent
pathway is a prime target of hippocampus-dependent cognitive deficits with aging.
Understanding the processes that specifically affect serine racemase during aging
could thus provide key insights into the treatment of memory deficits in the
elderly.

Copyright © 2009. Published by Elsevier Inc.

DOI: 10.1016/j.neurobiolaging.2009.09.001
PMID: 19800712 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus