A critical role for the glial-derived neuromodulator D-serine in the age-related deficits of cellular mechanisms of learning and memory.
Age-associated deficits in learning and memory are closely correlated with impairments of synaptic plasticity. Analysis of N-methyl-D-aspartate receptor (NMDAr)-dependent long-term potentiation (LTP) in CA1 hippocampal slices indicates that the glial-derived neuromodulator D-serine is required for the induction of synaptic plasticity. During aging, the content of D-serine and the expression of its synthesizing enzyme serine racemase are significantly decreased in the hippocampus. Impaired LTP and NMDAr-mediated synaptic potentials in old rats are rescued by exogenous D-serine. These results highlight the critical role of glial cells and presumably astrocytes, through the availability of D-serine, in the deficits of synaptic mechanisms of learning and memory that occur in the course of aging.
Mothet
J P
JP
Neurobiologie de la Croissance et de la Sénescence, UMR 549 INSERM, Faculté de Médecine, Université Paris-Descartes, 2 ter rue d'Alésia, 75014 Paris, France.
Rouaud
E
E
Sinet
P-M
PM
Potier
B
B
Jouvenceau
A
A
Dutar
P
P
Videau
C
C
Epelbaum
J
J
Billard
J-M
JM
D000375:Aging / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008568:Memory / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012694:Serine / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine