二甲双胍可减轻三甲基锡诱导的认知障碍和海马神经变性

IF 3.6 4区 医学 Q3 CELL BIOLOGY Cellular and Molecular Neurobiology Pub Date : 2024-10-23 DOI:10.1007/s10571-024-01502-4
Mahdieh Taheri, Mehrdad Roghani, Reza Sedaghat
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引用次数: 0

摘要

神经毒剂三甲基锡(TMT)会引发认知障碍和海马神经变性。三甲基锡是研究阿尔茨海默病(AD)发病机制和治疗方法的有用研究工具。尽管抗糖尿病药物二甲双胍已显示出良好的神经保护作用,但其在神经退行性疾病中的确切作用模式仍有待进一步阐明。在这项研究中,我们探讨了二甲双胍是否能减轻TMT认知障碍和海马神经退行性变。为了诱导类似于AD的表型,我们对TMT进行了静脉注射(8毫克/千克),并连续3周每天口服二甲双胍200毫克/千克。结果表明,二甲双胍可减轻TMT组在巴恩斯迷宫、新物体识别(NOR)任务和Y迷宫中的学习和记忆损伤,减轻海马氧化、炎症和细胞死亡/凋亡因子,还可逆转神经退行性变相关蛋白,如presenilin 1和p-Tau。二甲双胍治疗后,作为能量平衡关键调节因子的AMP激活蛋白激酶(AMPK)的海马水平也得到了改善。此外,二甲双胍还降低了海马乙酰胆碱酯酶(AChE)活性和胶质纤维酸性蛋白(GFAP)阳性反应,并防止了CA1锥体神经元的丢失。这项研究表明,二甲双胍可减轻TMT诱导的神经退行性变,这可能为开发新的治疗药物以应对神经毒性条件下的认知障碍铺平道路。
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Metformin Mitigates Trimethyltin-Induced Cognition Impairment and Hippocampal Neurodegeneration.

The neurotoxicant trimethyltin (TMT) triggers cognitive impairment and hippocampal neurodegeneration. TMT is a useful research tool for the study of Alzheimer's disease (AD) pathogenesis and treatment. Although the antidiabetic agent metformin has shown promising neuroprotective effects, however, its precise modes of action in neurodegenerative disorders need to be further elucidated. In this study, we investigated whether metformin can mitigate TMT cognition impairment and hippocampal neurodegeneration. To induce an AD-like phenotype, TMT was injected i.p. (8 mg/kg) and metformin was administered daily p.o. for 3 weeks at 200 mg/kg. Our results showed that metformin administration to the TMT group mitigated learning and memory impairment in Barnes maze, novel object recognition (NOR) task, and Y maze, attenuated hippocampal oxidative, inflammatory, and cell death/pyroptotic factors, and also reversed neurodegeneration-related proteins such as presenilin 1 and p-Tau. Hippocampal level of AMP-activated protein kinase (AMPK) as a key regulator of energy homeostasis was also improved following metformin treatment. Additionally, metformin reduced hippocampal acetylcholinesterase (AChE) activity, glial fibrillary acidic protein (GFAP)-positive reactivity, and prevented the loss of CA1 pyramidal neurons. This study showed that metformin mitigated TMT-induced neurodegeneration and this may pave the way to develop new therapeutics to combat against cognitive deficits under neurotoxic conditions.

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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
期刊最新文献
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