Loss of presenilin 2 function age-dependently increases susceptibility to kainate-induced acute seizures and blunts hippocampal kainate-type glutamate receptor expression.

ABSTRACT: Presenilin 2 (PSEN2) gene variants increase the risk of early-onset Alzheimer's disease (AD). AD patients with PSEN2 variants have increased risk of unprovoked seizures versus age-matched healthy controls, yet few studies have interrogated PSEN2 contributions to seizures, and fewer have done so with aging. PSEN2 variant mice also do not exhibit amyloid-β (Aβ) accumulation, allowing for the assessment of Aβ-independent contributions to seizure risk in AD. Critically, PSEN proteolytic capacity may regulate hippocampal kainate-type glutamate receptors (KARs), with PSEN deletion reducing KAR availability and synaptic transmission in vitro (Barthet et al 2022). Kainic acid (KA) is a naturally occurring KAR agonist that acutely evokes severe seizures in mice. We thus hypothesized that PSE

SUBMITTER: Robinson-Cooper L 

PROVIDER: S-EPMC12439899 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature