Impairment of kindling development in phospholipase C?1 heterozygous mice.

ABSTRACT: Elucidating molecular mechanisms underlying limbic epileptogenesis may reveal novel targets for preventive therapy. Studies of TrkB mutant mice led us to hypothesize that signaling through a specific phospholipase (PLC), PLC?1, promoted development of kindling.To test this hypothesis, we examined the development of kindling in PLC?1 heterozygous mice. We also examined the cellular and subcellular location of PLC?1 in adult wild-type mice.The development of kindling was impaired in PLC?1 heterozygous mice compared to wild-type controls. PLC?1 immunoreactivity was localized to the soma and dendrites of both excitatory and inhibitory neurons in the hippocampus of adult mice.This study implicates PLC?1 signaling as the dominant pathway by which TrkB activation promotes limbic epileptogenesis. Its cellular localization places PLC?1 in a position to modify the efficacy of both excitatory and inhibitory synaptic transmission. These findings advance PLC?1 as a novel target for therapies aimed at preventing temporal lobe epilepsy induced by status epilepticus.

SUBMITTER: He XP 

PROVIDER: S-EPMC4046707 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature