Alterations in excitotoxicity and prostaglandin metabolism in a transgenic mouse model of Alzheimer's disease.

To address the potential impact of presenilin mutations on the prostaglandin metabolism in a neurodegenerative model of glutamatergic excitotoxicity, we injected kainic acid intraperitoneally (30mg/kg body weight) into mice over-expressing the human N141I mutation of presenilin-2, which is known to cause an early-onset form of Alzheimer's disease. We compared the seizure activity as well as seizure lethality in 2- and 6-month-old mice, transgenic for the above-mentioned point mutation, and their wildtype littermates and found that mice harboring the hN141I mutation showed a relative resistance to excitotoxic treatment. This was associated with a constituitively reduced expression of the cyclooxygenases COX-1 and COX-2 in the hippocampus of N141I presenilin-2 mice and a reduced induction of COX-2 expression post-kainate injection.