Group II Metabotropic Glutamate Receptors Reduce Apoptosis and Regulate BDNF and GDNF Levels in Hypoxic-Ischemic Injury in Neonatal Rats
| Autor: | Ewelina Bratek-Gerej, Apolonia Ziembowicz, Elzbieta Salinska |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Brain-Derived Neurotrophic Factor
Organic Chemistry hypoxia-ischemia birth asphyxia group II metabotropic glutamate receptors LY379268 NAAG neuroprotection apoptosis neurotrophins Apoptosis General Medicine Dipeptides Bridged Bicyclo Compounds Heterocyclic Receptors Metabotropic Glutamate Catalysis Computer Science Applications Rats Inorganic Chemistry Asphyxia Neuroprotective Agents Animals Newborn Brain Injuries Animals Glial Cell Line-Derived Neurotrophic Factor Physical and Theoretical Chemistry Amino Acids Hypoxia Molecular Biology Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 13; Pages: 7000 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23137000 |
| Popis: | Birth asphyxia causes brain injury in neonates, but a fully successful treatment has yet to be developed. This study aimed to investigate the effect of group II mGlu receptors activation after experimental birth asphyxia (hypoxia-ischemia) on the expression of factors involved in apoptosis and neuroprotective neurotrophins. Hypoxia-ischemia (HI) on 7-day-old rats was used as an experimental model. The effects of intraperitoneal application of mGluR2 agonist LY379268 (5 mg/kg) and the specific mGluR3 agonist NAAG (5 mg/kg) (1 h or 6 h after HI) on apoptotic processes and initiation of the neuroprotective mechanism were investigated. LY379268 and NAAG applied shortly after HI prevented brain damage and significantly decreased pro-apoptotic Bax and HtrA2/Omi expression, increasing expression of anti-apoptotic Bcl-2. NAAG or LY379268 applied at both times also decreased HIF-1α formation. HI caused a significant decrease in BDNF concentration, which was restored after LY379268 or NAAG administration. HI-induced increase in GDNF concentration was decreased after administration of LY379268 or NAAG. Our results show that activation of mGluR2/3 receptors shortly after HI prevents brain damage by the inhibition of excessive glutamate release and apoptotic damage decrease. mGluR2 and mGluR3 agonists produced comparable results, indicating that both receptors may be a potential target for early treatment in neonatal HI. |
| Databáze: | OpenAIRE |
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