Maternal Metformin Administration During the Pre-Gestation Period Improves Transient Cerebral Ischemia Injury in Male...

Area of Science:

• Neuroscience
• Pharmacology
• Epigenetics

Background:

• Maternal interventions, potentially via epigenetic mechanisms, can influence offspring cerebral ischemia.
• Metformin activates the AMP-activated protein kinase (AMPK) pathway and shows neuroprotective effects in cerebral ischemia.

Purpose of the Study:

• To investigate the impact of maternal metformin administration on cerebral ischemia in offspring.
• To determine if metformin's effects are mediated through the activation of the AMPK pathway.

Main Methods:

• Female rats received metformin (200 mg/kg) for two weeks before mating.
• Offspring (60 days old) underwent two-vessel occlusion (2VO) to induce cerebral ischemia.
• Neurological deficits and memory-related tests were performed on the offspring.

Main Results:

• Maternal metformin administration significantly reduced neurological deficits and improved memory in offspring post-cerebral ischemia.
• Key molecular changes observed include increased brain-derived neurotrophic factor (BDNF), c-fos, p-AMPK/AMPK ratio, and histone H3K9 acetylation in the hippocampus.
• The Bcl-2/Bax ratio declined, indicating reduced apoptosis.

Conclusions:

• Maternal metformin intervention, through AMPK activation, ameliorates cerebral ischemia consequences in offspring.
• The treatment enhances spatial memory, neural plasticity, and hippocampal bioenergetics and histone acetylation.
• This suggests a promising therapeutic strategy for mitigating perinatal brain injury.