Exercise hormone irisin prevents physical inactivity-induced cognitive decline in mice
Exercise hormone irisin prevents physical inactivity-induced cognitive decline in mice
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DOI：
10.1016/j.bbr.2022.114008
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发表时间：
2022-07-31
影响因子：
2.7
通讯作者：
Mikami，Toshio
中科院分区：
文献类型：
--
作者：
Park，Jonghyuk;Kim，Jimmy;Mikami，Toshio
我们以前曾报道过，身体不活动（PI）导致认知能力下降和抑郁状态，这是改善定期锻炼。然而，运动的预防作用的机制仍然不清楚。Irisin最近被确定为运动诱导的肌因子，可改善认知障碍。体育锻炼期间血浆鸢尾素水平增加;因此，PI可通过降低血浆鸢尾素导致认知功能下降。因此，本研究的目的是检查是否鸢尾素与PI和运动改变的认知下降和精神恶化。将小鼠在PI笼中饲养8周，其生活空间是标准笼的六分之一。同时，在存在或不存在鸢尾素中和抗体的情况下，使小鼠进行定期运动。PI增加附睾脂肪量，而不增加体重，肌肉质量，或血浆皮质酮水平。此外，PI诱导焦虑，抑郁状态，并在工作记忆下降。相反，PI后定期运动可升高血浆中的鸢尾素水平，并增加骨骼肌中含纤连蛋白III型结构域5（FNDC 5）和过氧化物酶体增殖物激活受体γ激活因子1α的表达。有规律的运动还增加海马脑源性神经营养因子（BDNF）的表达和BrdU阳性细胞，减轻PI引起的认知功能下降和智力退化。运动的有益效果受到鸢尾素中和抗体的影响。此外，血浆鸢尾素水平与工作记忆、海马BDNF水平和海马细胞增殖呈正相关。这些发现表明，运动诱导的鸢尾素是维持PI状态下的认知功能的关键。
We previously reported that physical inactivity (PI) induces cognitive decline and depressive states, which were ameliorated by regular exercise. However, the mechanism underlying the preventive effect of exercise remains unelucidated. Irisin has recently been identified as an exercise-inducible myokine that improves cognitive impairment. Plasma irisin levels increase during physical exercise; therefore, PI could lead to a decline in cognitive function by reducing plasma irisin. Therefore, this study aimed to examine whether irisin is associated with cognitive decline and mental deterioration altered by PI and exercise. The mice were housed for eight weeks in the PI cage, whose living space was one-sixth that of a standard cage. Simultaneously, the mice were subjected to regular exercise in the presence or absence of an irisin-neutralizing antibody. PI increased the epididymal fat mass without increasing body weight, muscle mass, or plasma corticosterone levels. Additionally, PI induced anxiety, depressive states, and a decline in working memory. In contrast, regular exercise after PI elevated irisin levels in plasma and increased fibronectin type III domain-containing 5 (FNDC5) and peroxisome proliferator-activated receptor gammacoactivator 1α expression in skeletal muscle. Regular exercise also increased hippocampal brain-derived neurotrophic factor (BDNF) expression and BrdU-positive cells, alleviating cognitive decline and mental deterioration induced by PI. The beneficial effects of exercise were compromised by the administration of an irisin-neutralizing antibody. Moreover, plasma irisin level was positively correlated with working memory, hippocampal BDNF levels, and hippocampal cell proliferation. These findings suggest that exercise-inducible irisin is critical for maintaining cognitive function in the PI state.