Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK 99775, USA.
Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK 99775, USA
Dis Model Mech. 2021 Jan 26;14(1):dmm047217. doi: 10.1242/dmm.047217.
The development of animal models is a critical step for exploring the underlying pathophysiological mechanisms of major affective disorders and for evaluating potential therapeutic approaches. Although most neuropsychiatric research is performed on nocturnal rodents, differences in how diurnal and nocturnal animals respond to changing photoperiods, combined with a possible link between circadian rhythm disruption and affective disorders, has led to a call for the development of diurnal animal models. The need for diurnal models is most clear for seasonal affective disorder (SAD), a widespread recurrent depressive disorder that is linked to exposure to short photoperiods. Here, we briefly review what is known regarding the etiology of SAD and then examine progress in developing appropriate diurnal rodent models. Although circadian disruption is often invoked as a key contributor to SAD, a mechanistic understanding of how misalignment between endogenous circadian physiology and daily environmental rhythms affects mood is lacking. Diurnal rodents show promise as models of SAD, as changes in affective-like behaviors are induced in response to short photoperiods or dim-light conditions, and symptoms can be ameliorated by brief exposure to intervals of bright light coincident with activity onset. One exciting avenue of research involves the orexinergic system, which regulates functions that are disturbed in SAD, including sleep cycles, the reward system, feeding behavior, monoaminergic neurotransmission and hippocampal neurogenesis. However, although diurnal models make intuitive sense for the study of SAD and are more likely to mimic circadian disruption, their utility is currently hampered by a lack of genomic resources needed for the molecular interrogation of potential mechanisms.
动物模型的发展对于探索主要情感障碍的潜在病理生理机制以及评估潜在的治疗方法至关重要。尽管大多数神经精神学研究都是在夜间活动的啮齿动物上进行的,但昼夜动物对光照周期变化的反应方式的差异,加上昼夜节律紊乱与情感障碍之间可能存在联系,这促使人们呼吁开发昼夜动物模型。对于季节性情感障碍(SAD),昼夜模型的需求最为明显,SAD 是一种广泛存在的复发性抑郁障碍,与暴露于短光照周期有关。在这里,我们简要回顾了 SAD 的病因学知识,然后检查了开发适当的昼夜啮齿动物模型的进展。尽管昼夜节律紊乱经常被认为是 SAD 的一个关键因素,但对于内源性昼夜生理与日常环境节律之间的失协调如何影响情绪的机制理解还很缺乏。昼夜活动的啮齿动物作为 SAD 模型具有很大的潜力,因为它们在短光照周期或弱光条件下会引起类似情感的行为变化,并且通过短暂暴露于与活动开始时间一致的明亮光间隔可以缓解症状。一个令人兴奋的研究途径涉及食欲素系统,该系统调节 SAD 中紊乱的功能,包括睡眠周期、奖励系统、进食行为、单胺能神经递质传递和海马神经发生。然而,尽管昼夜模型对于 SAD 的研究具有直观意义,并且更有可能模拟昼夜节律紊乱,但由于缺乏用于分子研究潜在机制的基因组资源,它们的应用目前受到限制。