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Maternal metformin administration during the pre-gestation period improves memory in transient cerebral ischemia injury in rats’ male offspring
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Ghorbangol Ashabi   , Reyhaneh Vaali , Fardin Sehati , Mina Ranjbaran , Marjan Nikbakhtzadeh , Abbas Zareei , Iraj Ahmadi |
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Abstract: (401 Views) |
Introduction: In recent times, research has been directed towards epigenetic mechanisms and their role in the development of ischemic stroke, including DNA methylation and histone modifications. Studies indicated that metformin (met) administration in the prenatal period had a long-term effect on the metabolic phenotype, such as decreased body weight of mice fetuses and altered glucose tolerance of offspring. We have investigated the effect of maternal Adenosine monophosphate-activated protein kinase (AMPK) pathway activation by metformin administration on cerebral ischemia in offspring.
Methods and Materials: Animals were separated into four groups: sham, 2-vessels occlusion (2VO), Met+2VO, Met+compound c (AMPK inhibitor (CC)) +2VO. Female rats in the metformin group were given metformin at a dosage of 200mg/kg for a period of 2 weeks. Afterward, female rats were mated with male rats. Sixty-days-old offspring underwent cerebral ischemia and then memory-related tests were done.
Results: Current data revealed that the neurological deficits score was reduced in the Met+2VO group (P<0.001), and the memory increased (P<0.001) in comparison to the 2VO group. The Bcl-2/Bax ratio declined in the metformin group (P<0.001) while the Brain-Derived Neurotropic Factor (BDNF), c-fos, p-AMPK/AMPK ratio and Histone H3K9 acetylation in the hippocampus augmented significantly compared to the 2VO group (P<0.001).
Conclusion: These findings indicated that the metformin intervention via AMPK activation could improve movement disability, enhance spatial memory, increase neural plasticity, and augment the bioenergetics state and epigenetic index in the hippocampus of the offspring.
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| Keywords: Metformin, ischemia, memory, offspring, AMPK, rats |
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Full-Text [PDF 311 kb]
(82 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2023/11/25 | Accepted: 2023/08/23 | Published: 2023/08/23
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