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光照可挽救在类似冬季光照周期下的昼行性啮齿动物的昼夜节律行为和大脑多巴胺异常。

Light rescues circadian behavior and brain dopamine abnormalities in diurnal rodents exposed to a winter-like photoperiod.

机构信息

Institute of Cellular and Integrative Neurosciences, CNRS-UPR3212, 5 rue Blaise Pascal, 67084, Strasbourg Cedex, France.

Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.

出版信息

Brain Struct Funct. 2018 Jul;223(6):2641-2652. doi: 10.1007/s00429-018-1655-8. Epub 2018 Mar 20.

Abstract

Seasonal affective disorder (SAD), beyond mood changes, is characterized by alterations in daily rhythms of behavior and physiology. The pathophysiological conditions of SAD involve changes in day length and its first-line treatment is bright light therapy. Animal models using nocturnal rodents have been studied to elucidate the neurobiological mechanisms of depression, but might be ill suited to study the therapeutic effects of light in SAD since they exhibit light-aversive responses. Here Arvicanthis ansorgei, a diurnal rodent, was used to determine behavioral, molecular and brain dopamine changes in response to exposure to a winter-like photoperiod consisting of a light-dark cycle with 8 h of light, under diminished light intensity, and 16 h of darkness. Furthermore, we evaluated whether timed-daily bright light exposure has an effect on behavior and brain physiology of winter-like exposed animals. Arvicanthis under a winter-like condition showed alterations in the synchronization of the locomotor activity rhythm to the light-dark cycle. Moreover, alterations in day-night activity of dopaminergic neurotransmission were revealed in the nucleus accumbens and the dorsal striatum, and in the day-night clock gene expression in the suprachiasmatic nucleus. Interestingly, whereas dopamine disturbances were reversed in animals exposed to daily light at early or late day, altered phase of the daily rhythm of locomotion was reverted only in animals exposed to light at the late day. Moreover, Per2 gene expression in the SCN was also affected by light exposure at late day in winter-like exposed animals. These findings suggest that light induces effects on behavior by mechanisms that rely on both circadian and rhythm-independent pathways influencing the dopaminergic circuitry. This last point might be crucial for understanding the mechanisms of non-pharmacological treatment in SAD.

摘要

季节性情感障碍(SAD)除了情绪变化外,还表现为行为和生理节律的改变。SAD 的病理生理状况涉及到日照时间的变化,其一线治疗方法是明亮光照疗法。已经使用夜间活动的啮齿动物进行了动物模型研究,以阐明抑郁的神经生物学机制,但由于它们表现出对光的厌恶反应,可能不适合研究光在 SAD 中的治疗效果。在这里,我们使用昼行性啮齿动物安氏长尾狸鼠来确定在冬季光照条件下,即光照-黑暗周期为 8 小时,光照强度降低,16 小时黑暗,对行为、分子和大脑多巴胺的影响。此外,我们还评估了定时每日强光照射是否会对冬季光照暴露动物的行为和大脑生理学产生影响。在冬季光照条件下,安氏长尾狸鼠的运动活动节律对光-暗周期的同步性发生了改变。此外,在伏隔核和背侧纹状体中,昼夜多巴胺能神经传递的活性发生了改变,在视交叉上核中昼夜节律基因表达也发生了改变。有趣的是,虽然在早期或晚期接受每日光照的动物中,多巴胺紊乱得到了逆转,但只有在晚期接受光照的动物中,昼夜运动节律的相位才得到了逆转。此外,在冬季光照暴露的动物中,视交叉上核中的 Per2 基因表达也受到了晚期光照的影响。这些发现表明,光通过依赖于昼夜节律和非节律途径的机制对行为产生影响,从而影响多巴胺能回路。这最后一点对于理解 SAD 中非药物治疗的机制可能至关重要。

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