title: How does prolonged caloric restriction ameliorate age-related impairment of long-term potentiation in the hippocampus?
abstract: Prolonged dietary restriction has been reported to suppress age-induced phenomena. In order to investigate how prolonged caloric restriction reduces age-related deterioration of hippocampal synaptic transmission, we compared the levels of major hippocampal polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid between 4- and 26-month-old rats. The Ca(2+) responses upon perfusion of NMDA or 30 mM K(+) between 4- and 26-month-old rats with prolonged dietary restriction were also compared using the fluorescent probe Fura-2. A decrease in membrane arachidonic acid is thought to be a major causal factor in the age-related impairment of long-term potentiation. Long-term caloric restriction seems to increase arachidonic acid levels regardless of age. However, there is no significant difference of hippocampal arachidonic acid levels between in freely feeding 4- and 26-month-old rats. Similar results were obtained from the measurement of hippocampal docosahexaenoic acid levels. Under caloric restriction, the 500 microM N-methyl-D-aspartate-induced Ca(2+) response was greatly reduced by aging, while the 30 mM K(+)-induced Ca(2+) response was not affected. In our preliminary data, the amplitude of the population spike after tetanic stimulation did not differ between 4- and 26-month-old rats under caloric restriction, while 50 microM of 2-amino-5-phosphonovaleric acid, a N-methyl-D-aspartate antagonist, markedly inhibited a potentiation of the population spike in 4-month-old rats, but with negligible inhibition in 26-month-old rats. From these results, an age-related impairment of hippocampal excitatory synaptic transmission may not be solely due to the reduction of membrane arachidonic acid. Caloric restriction might prevent age-related reduction in hippocampal synaptic transmission by enhancing non-N-methyl-D-aspartate mechanisms.
authors.affiliation: Laboratory of Molecular and Cellular Neurogenetics, LTA Medical Corporation, Fukuoka 810-0064, Japan. mokada@med.osaka-cu.ac.jp
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Okada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Amamoto
authors.forename: Ryuji
authors.initials: R
authors.lastname: Urae
authors.forename: Susumu
authors.initials: S
authors.lastname: Ando
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yazawa
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D031204:Caloric Restriction; D004281:Docosahexaenoic Acids / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005508:Food Deprivation / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005231:Fatty Acids, Unsaturated; D008563:Membrane Lipids; D016194:Receptors, N-Methyl-D-Aspartate; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D016202:N-Methylaspartate; C056639:2-amino-5-phosphopentanoic acid; D015763:2-Amino-5-phosphonovalerate; D014633:Valine; D002118:Calcium