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Age‐related changes in NMDA‐induced [ 3 H]acetylcholine release from brain slices of senescene‐accelerated mouse
Author(s) -
Zhao XueHui,
Kitamura Yoshihisa,
Nomura Yasuyuki
Publication year - 1992
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/0736-5748(92)90040-7
Subject(s) - nmda receptor , acetylcholine , phencyclidine , glutamate receptor , chemistry , choline , endocrinology , medicine , cholinergic , pharmacology , biology , biochemistry , receptor
From the brain slices of normal mice (ddY strain, subcloned from dd strain in National Institute of Health in Japan), N‐methyl‐ d ‐aspartic acid (NMDA) at 0.01~1 mM evoked [ 3 H]acetylcholine (ACh) release in a concentration dependent manner. [ 3 H]ACh release evoked by 1 mM NMDA was significantly inhibited by 2‐amino‐5‐phosphonovaleric acid (APV), phencyclidine (PCP) and 5‐methyl‐10,11‐dihydroxy‐5H‐dibenzo[a,d]cyclo‐hepten‐5,10‐imine maleate (MK‐801). The effects of NMDA were not seen in the Ca 2+ free medium and were inhibited by physiological concentration (0.83 mM) of Mg 2+ . NMDA seems to cause ACh release from nerve terminals through the receptorion channel mediated mechanism in the mouse brain. Based upon these results, we determined the activity of a high K + ‐ or NMDA‐evoked [ 3 H] ACh release using prone/8 strain of senescence‐accelerated mouse (SAM‐P/8) (a murine model of accelerated aging and memory dysfunction) and SAM‐resistance/1 strain (SAM‐R/1) (normal aging mice as the control) and these release activities were compared between both strains and during aging. [ 3 H]ACh release evoked by 30 mM KCl was significantly lower than that of age‐matched SAM‐R/1 at 9 and 12 months. NMDA evoked the [ 3 H]ACh release at 2, 6, 10 and 14 months in R/1 mice. In SAM‐P/8 mice the activity of NMDA‐evoked release was seen at 2 months, but markedly decreased afterwards. Nonsignificant difference was observed on the uptake of [ 3 H]choline and on the spontaneous release of [ 3 H]ACh between SAM‐P/8 and SAM‐R/1 strains, and during aging. These results suggest: (1) NMDA receptor‐ion channels are involved in the ACh release from nerve terminals in the CNS; (2) the NMDA‐evoked ACh release is decreased after 6 months in SAM‐P/8 mice but not in SAM‐R/1 mice; and (3) the high K + ‐evoked ACh release is decreased at an earlier age in SAM‐P/8 than it is in SAM‐R/1. These results suggest that the NMDA‐ and cholinergic‐system in the CNS seems to be deficient in SAM‐P/8 and that this deterioration may be a possible cause for their dysfunction of learning and memory.