Impairment of kindling development in phospholipase Cγ1 heterozygous mice

Authors

  • Xiao Ping He,

    1. Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina, U.S.A
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  • Renren Wen,

    1. The Blood Research Institute, Blood Center of Wisconsin, Milwaukee, Wisconsin, U.S.A
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  • James O. McNamara

    Corresponding author
    1. Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina, U.S.A
    2. Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, U.S.A
    3. Department of Pharmacology and Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina, U.S.A
    • Address correspondence to James O. McNamara, M.D., Department of Neurobiology, Duke University Medical Center, P O Box 3676, Durham, NC 27710, U.S.A. E-mail: jmc@neuro.duke.edu

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Summary

Objective

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), PLCγ1, promoted development of kindling.

Methods

To test this hypothesis, we examined the development of kindling in PLCγ1 heterozygous mice. We also examined the cellular and subcellular location of PLCγ1 in adult wild-type mice.

Results

The development of kindling was impaired in PLCγ1 heterozygous mice compared to wild-type controls. PLCγ1 immunoreactivity was localized to the soma and dendrites of both excitatory and inhibitory neurons in the hippocampus of adult mice.

Significance

This study implicates PLCγ1 signaling as the dominant pathway by which TrkB activation promotes limbic epileptogenesis. Its cellular localization places PLCγ1 in a position to modify the efficacy of both excitatory and inhibitory synaptic transmission. These findings advance PLCγ1 as a novel target for therapies aimed at preventing temporal lobe epilepsy induced by status epilepticus.

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