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Reduced serine racemase expression contributes to age-related deficits in hippocampal cognitive function
- Source :
- Neurobiology of Aging, Neurobiology of Aging, Elsevier, 2011, 32 (8), pp.1495-1504. ⟨10.1016/j.neurobiolaging.2009.09.001⟩, Neurobiology of Aging, 2011, 32 (8), pp.1495-1504. ⟨10.1016/j.neurobiolaging.2009.09.001⟩
- Publication Year :
- 2011
- Publisher :
- HAL CCSD, 2011.
-
Abstract
- 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. © 2009 Published by Elsevier Inc.
- Subjects :
- Male
Senescence
Aging
medicine.medical_specialty
Racemases and Epimerases
Hippocampus
Hippocampal formation
Biology
Gene Expression Regulation, Enzymologic
Serine
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Animals
Rats, Wistar
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
Memory Disorders
0303 health sciences
General Neuroscience
Long-term potentiation
Rats
Endocrinology
Serine racemase
Synaptic plasticity
NMDA receptor
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Neurology (clinical)
Geriatrics and Gerontology
Cognition Disorders
Neuroscience
030217 neurology & neurosurgery
Signal Transduction
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 01974580
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Aging, Neurobiology of Aging, Elsevier, 2011, 32 (8), pp.1495-1504. ⟨10.1016/j.neurobiolaging.2009.09.001⟩, Neurobiology of Aging, 2011, 32 (8), pp.1495-1504. ⟨10.1016/j.neurobiolaging.2009.09.001⟩
- Accession number :
- edsair.doi.dedup.....03af935f7c01850f93d79ed149355b0c