Therapeutic Effect of Metformin on Necrotic Cell Death of Hippocampal Cells and Improvement of Spatial Memory in the Fetal Rat of Model Alcohol Spectrum Disorders

Subject Areas : Journal of Animal Biology

Maryam Sabzali ¹ , Akram Eidi ² , Mahdi Khaksari ³ , Hossin Khastar ⁴

1 - Department of Biology, Islamic Azad University, Science & Research Institute, Tehran, Iran
2 - Department of Biology, Islamic Azad University, Science & Research Institute, Tehran, Iran
3 - Addiction Research Center, Shahroud University of Medical Sciences, Shahroud, Iran
4 - Addiction Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

Received: 2021-06-16 Accepted : 2021-08-03 Published : 2022-05-22

Keywords: ethanol, Hippocampus, Metformin, spatial memory, Necrosis,

Abstract :

Exposure to alcohol during pregnancy causes a wide range of long-term physiological and behavioral effects, collectively referred to as fetal alcohol syndrome (FASD). Nervous disorders due to alcohol abuse in children with apoptosis in several areas of the brain such as the hippocampus is associated with activation of the oxidative-inflammatory cascade and high levels of nerve degeneration. Studies have shown that metformin (1,1-dimethyl hydrochloride), used as a first-line drug for the treatment of type 2 diabetes, can rapidly cross the blood-brain barrier (BBB) ​​and have neuroprotective effects in several diseases of the nervous system. The aim of this study was to assess the protective activities of metformin on memory impairment and neuronal necrosis in the rat hippocampus by postnatal alcohol exposure received by gavage on days 2-10 after birth. Moreover, infants received 20 and 40 mg/kg of metformin on days 2-10 after birth. To assess spatial memory, the Morris water maze test was performed 36 days after birth. After the behavioral test, nickel staining was performed to assess necrotic cells. The results revealed that metformin treatment could significantly improve spatial memory impairment (P <0.01) and significantly reduced necrotic neurons in the metformin treatment group compared to the ethanol group (P <0.01). Metformin has been shown to improve spatial memory impairment in neonatal rats exposed to ethanol and significantly prevent necrotic death of hippocampal neurons.

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