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Implication de la protéine kinase C dans les troubles bipolaires : vers de nouvelles cibles thérapeutiques

Abstract : Bipolar disorder is a devastating long-term disease characterized by alternate episodes of mania and depression. Despite extensive research, the molecular and cellular underpinnings of bipolar disorder remain to be fully elucidated. Protein kinase C (PKC) has emerged as a potential molecular target for the treatment of bipolar disorder. The present study investigated the role of PKC in manic- and depressive-like behaviors. Our results showed that PKC inhibition produced an antimanic-like effect not only in naive rats, but also in an animal model of mania based on sleep deprivation, that we have validated in our study. Interestingly, PKC inhibitors rescued the hippocampal cell proliferation deficits displayed by sleep-deprived animals. These proliferative and antimanic effects were independent, since blockade of cell proliferation did not abolish the antimanic efficacy of PKC inhibitors in the sleep deprivation model. At the same time, we showed that PKC activation had an antidepressant-like effect in naive rats, whereas its inhibition caused a depressive-like phenotype accompanied by a decrease in hippocampal cell proliferation. Taken together, our results demonstrate the involvement of the PKC system in regulating opposite facets of bipolar disorder, and support the hypothesis that an overactivation of the PKC signaling system may be crucial for the deficits of neuroplasticity associated with mania.
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https://tel.archives-ouvertes.fr/tel-00832777
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Submitted on : Tuesday, June 11, 2013 - 12:22:14 PM
Last modification on : Thursday, October 29, 2020 - 3:31:56 AM
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Erika Abrial. Implication de la protéine kinase C dans les troubles bipolaires : vers de nouvelles cibles thérapeutiques. Médecine humaine et pathologie. Université Claude Bernard - Lyon I, 2013. Français. ⟨NNT : 2013LYO10011⟩. ⟨tel-00832777⟩

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