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 protein 2 (APLP2). To date, little is known of the involvement of this protein in Alzheimer's disease or any other neurodegenerative condition. The present study set out to determine whether APLP2 expression could be modified in cultured rat cortical neurones exposed to an excitotoxic insult. Treatment of cultures with glutamate (500 microM) for 30 min resulted in increased lactate dehydrogenase liberation into the bathing medium 24 h after removal of the insult indicating neuronal damage. This was accompanied by a decrease in APLP2 recovery in the medium but no change in its intracellular level. Both the increase in LDH release and APLP2 recovery were prevented by pretreatment with the N-methyl-D-aspartate receptor antagonist MK-801. These data show that neuronal APLP2 metabolism is altered in response to an excitotoxic insult.