Age-related effects of the neuromodulator D-serine on neurotransmission and synaptic potentiation in the CA1 hippocampal area of the rat.
The effects of the co-agonist of the N-methyl-D-aspartate receptor (NMDAr) D-serine on glutamatergic neurotransmission and synaptic potentiation were studied in the CA1 hippocampal field of young (3-5 months old) and aged (25-27 months old) Sprague-Dawley rats using ex vivo extracellular electrophysiological recording techniques. Exogenous d-serine depressed fast neurotransmission mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate subtype of glutamate receptors in young but not in aged rats by acting on inhibitory glycinergic interneurons. In contrast, D-serine dose-dependently enhanced NMDAr-mediated synaptic responses in both groups of animals, but with a larger magnitude in aged rats, thus preventing the age-related decrease in NMDAr activation. D-serine also increased the magnitude of long-term potentiation in aged but not in young rats. Finally, D-serine levels were dramatically reduced in hippocampal tissues of aged rats. Taken together, these results indicate a weaker activation of the NMDAr glycine modulatory site by endogenous D-serine in aged animals, which accounts for a reduced NMDAr contribution to synaptic plasticity in ageing.
Junjaud
G
G
Neurobiologie de la Croissance et de la Sénescence, INSERM, Faculté de Médecine, Université Paris-Descartes, Paris, France.
Rouaud
E
E
Turpin
F
F
Mothet
J-P
JP
Billard
J-M
JM
D000375:Aging / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018698:Glutamic Acid / Q000502:physiology; D005998:Glycine / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009415:Nerve Net / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism; D012694:Serine / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D018698:Glutamic Acid; D005998:Glycine; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine