Forskolin As a Neuroprotector and Modulator of Glutamate-Evoked Ca2+ Entry into Cerebellar Neurons

Abstract

The analysis of neuronal viability of cerebellar neurons in primary culture during long-lasting (240 min) treatment with glutamate revealed that forskolin (1 μM), an adenylate cyclase activator, prevents apoptosis and necrosis of cells, thus exhibiting neuroprotective properties. As the cytotoxic action of glutamate causes an increase of the intracellular Ca²⁺ concentration, we further studied forskolin influence on glutamate-evoked Ca²⁺ responses of neurons. A short-time pretreatment with 1 μM forskolin significantly decreases Ca²⁺ entry into neurons during glutamate action. The obtained results demonstrate an important role of adenylate cyclase and cAMP in regulation of the Ca²⁺ entry into neurons and intracellular signaling pathways preventing neuronal death of cerebellar neurons in excytotoxic stress.