New evidence for a role of mGluR7 in astrocyte survival: Possible implications for neuroprotection

• Autorzy: Jantas D. , Lech T. , Golda S. , Pilc A. , Lason W.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: A specific activation of metabotropic glutamatergic receptor subtype 7 (mGluR7) by its allosteric agonist AMN082 has been shown to protect neuronal cells against various detrimental factors. It is well established that some of subtypes of mGluRs (e.g., mGluR5 or mGluR3) engage glia cells to more efficiently protect neurons against various harmful stimuli. AIM(S): We aimed to study the role of mGluR7 in glia and neuronal cell survival. METHOD(S): We used primary cortical glia cell cultures and cerebellar granule neurons (CGNs)from mGluR7+/+ and mGluR7-/- C57Bl/6J mice which were exposed to various cell damaging factors (staurosporine (St), doxorubicin (Dox)and low potassium (LP)). MTT reduction, LDH release and caspase-3 activity biochemical assays were used for assessment of cell damage. The mRNA expression level of various subtypes of mGluRs was measured by qPCR. RESULTS: We showed the expression of mGluR7 in glia cell cultures and demonstrated the higher toxicity of St and Dox in mGluR7-/- glia cells when compared to wild type one. Moreover, we found a partial protection mediated by AMN082 against St and Dox in mGluR7+/+ glia cells. However, we did not find any differences in vulnerability of CGNs derived from mGluR7+/+ and mGluR7-/- animals to the cell damaging action of LP, St or Dox under standard treatment. Intriguingly, when we primed both types of CGNs by culturing them overnight in LP medium, we found significant higher toxic action of St and Dox in mGluR7‑/‑ CGNs. Finally, we confirmed neuroprotective properties of AMN082 in CGNs and showed that this effect is stimuli‑ and development-dependent. CONCLUSIONS: Our data obtained in isolated glia and neuronal cellular models showed a protective potential of mGluR7‑specific agonist AMN082 and pro‑survival role of mGluR7 in glia cells which together with its already known direct role on neuronal cells could suggest its higher efficacy under in vivo conditions. FINANCIAL SUPPORT: 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.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.112-113

Twórcy

autor

Jantas D.

• Department of Experimental Neuroendocrinology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland

autor

Lech T.

• Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland

autor

Golda S.

• Department of Molecular Neuropharmacology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland

autor

Pilc A.

• Department of Neurobiology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland

autor

Lason W.

• Department of Experimental Neuroendocrinology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland