Anti-apoptotic and pro-survival effect of group ii metabotropic glutamate receptors (MgluR2/3) activation in an animal model of birth asphyxia

• Autorzy: Salinska E. , Ziembowicz A. , Bratek E.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Birth asphyxia results in serious damage of central nervous system or neonatal death. It was shown recently that group II metabotropic glutamate receptors (mGluR2/3) activation results in neuroprotection but the exact mechanism of this effect is not clear. AIM(S): The aim of present study was to investigate whether neuroprotective effect of mGluR2/3 activation is connected with inhibition of apoptosis and activation of pro-survival neurotrophic factors. METHOD(S): We used hypoxia-ischemia (HI) on 7-day old rat pups as animal model of birth asphyxia. Animals were anesthetized and the left common carotid artery was isolated, double-ligated and cut between the ligatures. After 60 min of recovery the pups were subjected to hypoxia (7.4% oxygen in nitrogen for 75 min.). Control pups were sham-operated. Animals were injected i.p. with specific mGluR2 (LY379268) and mGluR3 (NAAG) agonists 1h or 6h after HI (5 mg/kg of b.w.). The weight deficit ofthe ischemic brain hemisphere was measured and the expression of Bax, Bcl-2, HTR/OMI was examined. The damage in the hippocampal CA1 region was examined by Cresyl violet staining. Differences in the expression of neurotrophic factors (BDNF, GDNF, TGF –beta) were measured using ELISA. RESULTS: Our results show that application of mGluR2/3 agonists after HI reduce brain damage. Both applied agonists decreased weight loss in ischemic hemisphere independently on the time of application by 50% and reduced the damage of CA1 region of hippocampus. Both mGluR2/3 agonists inhibited HI induced increase in expression of Bax and HTR/OMI and restored, decreased after HI, expression of Bcl-2. LY379268 and NAAG applied 1h or 6h after HI increased TGF beta expression and expression of BDNF and GDNF in the ischemic brain hemisphere. CONCLUSIONS: Neuroprotective effect of mGluR2/3 activation after HI insult is connected with reduction of apoptotic processes and activation of pro-survival neurotrophic factors. FINANCIAL SUPPORT: This work was made under MMRC-KNOW 2013–2017 project.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.51

Twórcy

autor

Salinska E.

• Department of Neurochemistry, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Ziembowicz A.

• Department of Neurochemistry, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Bratek E.

• Department of Neurochemistry, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland