Light-intensity exercise improves memory dysfunction with the restoration of hippocampal MCT2 and miRNAs in type 2 diabetic mice
Light-intensity exercise improves memory dysfunction with the restoration of hippocampal MCT2 and miRNAs in type 2 diabetic mice
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DOI：
10.1007/s11011-022-01117-y
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发表时间：
2022-11
影响因子：
3.6
通讯作者：
Takeru Shima;Reika Kawabata-Iwakawa;Hayate Onishi;S. Jesmin;Tomonori Yoshikawa
中科院分区：
文献类型：
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作者：
Takeru Shima;Reika Kawabata-Iwakawa;Hayate Onishi;S. Jesmin;Tomonori Yoshikawa
与2型糖尿病（T2 DM）相关的认知能力下降是损害人类健康的危险因素。尽管轻度运动通过改变海马乳酸转运和神经营养因子来预防症状前T2 DM动物的海马记忆功能障碍，但轻度运动对晚期T2 DM动物的影响尚不清楚。在此，对T2 DM的动物模型ob/ob小鼠进行光强度运动（5.0 m/min），30 min/天，5天/周，持续4周。研究轻度运动对海马并发症、单羧酸转运体（MCT）mRNA表达和miRNA水平的影响。低强度运动可改善ob/ob小鼠海马记忆保持能力。轻度运动可改善T2 DM患者下调的海马Mct 2 mRNA水平。各组内Mct 1和Mct 4的海马mRNA水平无变化。基于miRNA测序，久坐的ob/ob小鼠表现出海马中71个miRNA上调，77个miRNA下调。此外，运动显著增加了T2 DM海马中的24种miRNAs，减少了4种miRNAs。运动逆转了T2 DM诱导的海马9种miRNA的改变，包括miR-200 a-3 p。我们的研究结果表明，海马中的miR-200 a-3 p/Mct 2可能是治疗T2 DM诱导的记忆功能障碍的临床靶点。
Cognitive decline associated with type 2 diabetes mellitus (T2DM) is a risk factor to impair human health. Although light-intensity exercise prevents hippocampal memory dysfunction in pre-symptomatic T2DM animals by altering hippocampal lactate transport and neurotrophic factors, the effects of light-intensity exercise in an advanced stage of T2DM animals remain unclear. Here, ob/ob mice, an animal model of T2DM, were subjected to light-intensity exercise (5.0 m/min) for 30 min/day, five days/week for four weeks. The effects of light-intensity exercise on hippocampal complications, mRNA expressions of monocarboxylate transporter (MCT), and miRNA levels were assessed. The light-intensity exercise improved hippocampal memory retention in ob/ob mice. Downregulated hippocampal Mct2 mRNA levels in T2DM were improved with light-intensity exercise. Hippocampal mRNA levels of Mct1 and Mct4 were unchanged within groups. Based on miRNA sequencing, sedentary ob/ob mice exhibited that 71 miRNAs were upregulated, and 77 miRNAs were downregulated in the hippocampus. In addition, the exercise significantly increased 24 miRNAs and decreased 4 miRNAs in the T2DM hippocampus. The exercise reversed T2DM-induced alterations of hippocampal 9 miRNAs, including miR-200a-3p. Our findings imply that miR-200a-3p/Mct2 in the hippocampus would be a possible clinical target for treating T2DM-induced memory dysfunction.