How does prolonged caloric restriction ameliorate age-related impairment of long-term potentiation in the hippocampus?

Mitsuko Okada, Hiroshi Nakanishi, Toshiaki Amamoto, Ryuji Urae, Susumu Ando, Kazuyoshi Yazawa, Michihiro Fujiwara

研究成果: ジャーナルへの寄稿学術誌査読

21 被引用数 (Scopus)


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 Ca2+ 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 μM N-methyl-D-aspartate-induced Ca2+ response was greatly reduced by aging, while the 30 mM K+-induced Ca2+ 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 μM 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.

ジャーナルMolecular Brain Research
出版ステータス出版済み - 3月 17 2003

!!!All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞および分子神経科学


「How does prolonged caloric restriction ameliorate age-related impairment of long-term potentiation in the hippocampus?」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。