Glutamate toxicity in rat cultured neurones: effects on amyloid precursor-like protein 2

Amyloid precursor protein, which gives rise to the A beta polypeptide found in senile plaques in the brains of patients with Alzheimer's disease, is a member of a family of proteins which includes amyloid precursor-like prote in 2 (APLP2). To date, little is known of the involvement of this protein i n Alzheimer's disease or any other neurodegenerative condition. The present study set out to determine whether APLP2 expression could be modified in c ultured rat cortical neurones exposed to an excitotoxic insult. Treatment o f cultures with glutamate (500 mu M) for 30 min resulted in increased lacta te dehydrogenase liberation into the bathing medium 24 h after removal of t he insult indicating neuronal damage. This was accompanied by a decrease in APLP2 recovery in the medium but no change in its intracellular level, Bot h the increase in LDH release and APLP2 recovery were prevented by pretreat ment with the N-methyl-D-aspartate receptor antagonist MK-801. These data s how that neuronal APLP2 metabolism is altered in response to an excitotoxic insult, (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.