Abstract— The non-metabolizable amino acid, 1-aminocyclopentane-l-carboxylic acid (ACPC), when administered to mice, induces primary degeneration of axons in the cerebellum, rostral spinal cord and peripheral nerves. One to 4 weeks after a single intraperitoneal injection of ACPC (0.5–2 mg/g body wt) in adult mice, the fresh and dry weights of brain, cerebellum and spinal cord were reduced compared with those of normal and pair-fed controls. The protein content of all CNS regions, but particularly that of the cerebellum and cervical spinal cord, was lowered in ACPC-treated mice relative to that of normal controls. Sciatic nerve protein was also decreased in mice following 2 mg/g of ACPC. Pair-fed controls exhibited protein deficits in the cerebellum and cervical spinal cord but to a significantly smaller degree. In ACPC-treated mice, the sulfatide content of spinal cord and peripheral nerve was reduced but that of brain was normal. Sphingomyelin levels in these three regions increased except in the brains of mice given 0.5 mg/g of ACPC where the levels fell.

The protein and sulfatide deficits were greatest in the regions which are known to exhibit the highest proportion of degenerating nerve fibers. The correlation of ACPC treatment with protein and sulfatide loss is consistent with the reported disruptive effects of ACPC on protein metabolism and with the involvement of proteins in sulfatide. metabolism. The protein deficits in pair-fed mice are considered in relation to the exacerbating effect of reduced dietary protein intake on ACPC neurotoxicity.