Increasing body of evidence suggests a neuroprotective potential of metabotropic glutamatergic receptor group III (mGluR III) stimulation, however the role of particular subtypes of these receptors (mGluR4, mGluR7, mGluR8) in apoptotic processes is not fully recognized. Of special interest is the study on the role of mGluR7 which is widely expressed throughout the brain and recently developed selective positive allosteric modulator of this receptor, AMN082 (N,N=-dibenzhydrylethane-1,2-diamine dihydrochloride) enables investigation the biological role of mGluR7. In the present study, firstly we evaluated the possible neuroprotective effects of AMN082 (0.001–1 µM) on neurotoxicity induced by various apoptotic [stimuli staurosporine (St), doxorubicin (Dox) and low potassium (LP)] in 7 DIV cerebellar granule cells (CGC). The data showed that AMN082 (0.1–1 µM) partially attenuated the cell death induced by St and LP, but not by Dox. Next, we investigated the role of mGluR7 in neuronal cell death by testing the vulnerability of CGC from wild and mGluR7KO animals to toxic action of St, Dox and LP. No differences between groups under basal conditions have been found. However, after primary deprivation of CGC cells from potassium in culture medium and secondary application of proapoptotic stimuli we observed the higher vulnerability of mGluR7KO CGC to cell damaging effect of St and Dox but not LP. Further experiments performed on cortical glia cells demonstrated higher toxic action of St and Dox in mGluR7KO cells when compared to wild type one. Additionally, in mGluR7KO glia cells we found higher basal and stimulated by St or Dox caspase-3 activity when compared to wild type one. The obtained data suggest that specific stimulation of mGluR7 by AMN082 could be protective against staurosporine and low-potassium induced neuronal ell death. Moreover, the presence of mGluR7 could be particularly important for survival of glia cells under harmful conditions. The study was supported by statutory funds for Institute of Pharmacology PAS and grant No NN405611638 from the Ministry of Science and Higher Education, Warsaw, Poland.
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.