Delayed treatments with pharmacological modulators of pre- and postsynaptic mGlu receptors rescue the hippocampus from kainate-induced neurodegeneration

Gene expression of mGluR2, mGluR3 and mGluR5 was evaluated in the hippocampus and frontal cortex in Wistar rats in 1 and 4 weeks after bilateral microinjection of kainic acid into the dorsal hippocampus. The time-course of the receptors' expression suggested their adaptive role in response on the induction of excitotoxicity. It was assumed that the decrease of kainate-induced neurodegeneration could be achieved through simultaneous activation of presynaptic mGluRs and inhibition of mGlu postsynaptic receptors. Both negative allosteric modulator of mGluR5, MPEP, and agonist of mGluR2, LY354740, were administered intraperitoneally 5 days after microinjection of kainic acid. As shown by histochemical studies with cresyl violet and Fluoro-Jade, kainate induced significant damage of hippocampal neurons in the CA3 and CA1 fields. Pharmacological treatment with the negative modulator of mGlu5 receptors in common with the agonist of mGluR2 decreased kainate-induced neurodegeneration in dorsal hippocampus.