beta-Amyloid peptide fragment 25-35 potentiates the calcium-dependent release of excitatory amino acids from depolarized hippocampal slices.
beta-Amyloid protein (beta AP) has been frequently associated with the neuropathology of Alzheimer's disease (AD), although the mechanisms by which it can induce neurodegeneration are still unknown. Some studies in hippocampal cultured neurons suggest that beta AP, particularly its fragment 25-35, may induce neural growth or render neurons more vulnerable to excitotoxic insults by a mechanism involving intracellular Ca2+ dyshomeostasis. We have studied the effect of fragment 25-35 on the release of endogenous amino acids from hippocampal slices of young adult (3-3.5-month-old) and aged (23-25-month-old) rats, under basal, K(+)-depolarization, and post-depolarization conditions, in the presence and absence of Ca2+. In both young and aged tissue, the basal release of amino acids was not affected by the peptide. By contrast, 1-hr preincubation of slices from young animals with 10 microM 25-35 fragment resulted in a 140% increase of glutamate and aspartate release stimulated by K+ depolarization, compared with the control-stimulated release. These effects were strictly dependent on external Ca2+. Neither the K(+)-stimulated release of gamma-amino butyric acid (GABA) nor the release of glycine, glutamine, taurine, or alanine, which was not stimulated by high K+, were affected. Substance P and a scrambled sequence of the 25-35 fragment were without any effect per se, but substance P blocked the stimulatory effect of fragment 25-35 on glutamate and aspartate release. In slices from aged rats the basal release of glutamate was significantly higher (260%) than that in young tissue, and the K(+)-induced release of both aspartate and glutamate was also higher.(ABSTRACT TRUNCATED AT 250 WORDS)
D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018846:Excitatory Amino Acids; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium