Evaluation of the effects of metformin as adenosine monophosphate-activated protein kinase activator on spatial learning and memory in a rat model of multiple sclerosis disease
Evaluation of the effects of metformin as adenosine monophosphate-activated protein kinase activator on spatial learning and memory in a rat model of multiple sclerosis disease
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DOI：
10.1016/j.biopha.2021.111932
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发表时间：
2021-07-22
影响因子：
7.5
通讯作者：
Mirshekar, Mohammad Ali
中科院分区：
文献类型：
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作者：
Arabmoazzen, Saiedeh;Mirshekar, Mohammad Ali
在多发性硬化症（MS）患者中，由于海马体的破坏，已检测到认知缺陷。认知功能障碍是多发性硬化症的常见症状之一。近年来的研究表明，二甲双胍（Met）在治疗疾病方面具有广泛的作用。在这里，我们试图研究作为腺苷一磷酸激活蛋白激酶（AMPK）激活剂的Met对MS诱导后海马齿状回（DG）神经元放电模式、运动协调和学习记忆丧失的保护作用。用溴化乙锭（EB）诱导大鼠海马MS。然后，用Met（200 mg/kg）处理大鼠两周。Morris水迷宫检测大鼠空间记忆和学习能力。从海马DG测量神经元单单位记录。断头后，分离双侧海马测定丙二醛（MDA）含量。Met + MS治疗组潜伏期和路径长度分别较对照组明显延长（P < 0.05，P < 0.01，P < 0.001）。MS大鼠在目标区的总时间百分比和峰/箱的平均数显著低于假手术组（p < 0.001），但二甲双胍治疗组（Met + MS）显著高于假手术组（p < 0.01，p < 0.001）。与未治疗组相比，MS大鼠中的Met治疗显著降低了MDA的浓度，MDA是脂质过氧化的指标。这些观察结果表明，在用Met处理的MS大鼠中，神经元活性、感觉-运动协调和空间记忆的改善的增加通过AMPK的增加而出现。
In patients with multiple sclerosis (MS) disease, cognitive deficits have been detected because of destruction of hippocampus. Cognitive impairment is one of the common signs in MS. Recent studies showed that metformin (Met) has wide-ranging effects in the treatment of diseases. Here, we have tried to study the preservative effects of Met as adenosine monophosphate-activated protein kinase (AMPK) activator on the hippocampus dentate gyrus (DG) neuronal firing pattern, motor coordination, and learning & memory loss following MS induction. The MS induction was done by local ethidium bromide (EB) injection into the rat hippocampus. Then, rats were treated with Met (200 mg/kg) for two weeks. Spatial memory and learning status were assessed using Morris water maze. A neuronal single-unit recording was measured from hippocampus DG. After decapitation, the bilateral hippocampi separated to measure malondialdehyde (MDA). Treatment with Met ameliorated latency times and path lengths (P < 0.05, P < 0.01, P < 0.001 in 1th, 2th, 3th and 4th days) in the Met + MS group respectively. The percent of total time spent in goal quarter and the average number of spikes/bin were decreased significantly in MS rats compared with the sham group (p < 0.001) but significantly increased in the metformin-treated MS group (Met + MS), (p < 0.01, p < 0.001). Met treatment in rats with MS significantly reduced the concentration of MDA, which is an indicator of lipid peroxidation compared to untreated groups. These observations show that increase of neuronal activity, sensory-motor coordination, and improvement of spatial memory in MS rats treated with Met appears via an increment of AMPK.