The Neuroprotective Effect of Forskolin and Its Influence of Mitochondrial Dysfunction in Neurons in Primary Rat Cerebellum Cultures
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Activation of cyclic adenosine monophosphate (cAMP) synthesis is known to lead to triggering of neuroprotective signal cascades. It is therefore interesting to assess the effects of forskolin as an activator of adenylate cyclase and cAMP production on the neurotoxic action of glutamate in rat cerebellar neurons and to identify the participants in this signal cascade. This approach was used in experiments with a protein kinase A (PKA) inhibitor, the protein kinase C (PKC) blocker chelerythrine, and the calmodulin-dependent kinase II (CaMKII) blocker KN93, which showed that the neuroprotective effect of forskolin (1 μM) on long-term (24 h) exposure to glutamate (100 μM) involves PKA and CaMKII. Additional analysis of the dynamics of the development of mitochondrial dysfunction on exposure to glutamate showed that forskolin can prevent the drop in mitochondrial membrane potential in rat cerebellar neurons typical of excitotoxic stress.
Keywordsneurodegeneration glutamate forskolin neuroprotection apoptosis mitochondrial potential
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