NEUROTOXICITY OF A NON‐METABOLIZABLE AMINO ACID, 1‐AMINOCYCLOPENTANE‐1‐CARBOXYLIC ACID: ANTAGONISM BY AMINO ACIDS IN CULTURES OF CEREBELLUM

Abstract

Abstract— The non‐metabolizable amino acid 1‐aminocyclopentane‐1‐carboxylic acid (ACPC) induced degeneration of myelinated axons but spared nerve cell bodies in well myelinated organotypic cultures of cerebellum. The ACPC concentrations used were comparable to those which induce axonal degeneration in vivo. Developing unmyelinated cultures were more sensitive to ACPC than mature cultures and newly myelinating axons appeared to be particularly affected. Supplementing the medium with amino acids, but not with vitamins, prevented toxicity at the lower concentrations of ACPC and afforded considerable protection against the highest concentrations. The protective effect of amino acids could not be accounted for by inhibition of intracellular ACPC transport. These results are considered in terms of other evidence indicating defective protein metabolism in ACPC‐treated mice.