Time: 10:30-12:00 on Tue.,June.13, 2023

Venue：E109, Biomedicine Hall

Speaker: Dr.Luoying Zhang

Host: Dr.Guangshuo Ou

Title: Human PERIOD3 Variants Lead to Winter Depression-Like Behaviors by Disrupting Glucocorticoid and Serotonin Homeostasis

Abstract：

Winter seasonal affective disorder (SAD, also known as winter depression) is characterized by predictable onset of depression in fall/winter months with spontaneous remission in spring/summer. Currently, we know little regarding the underlying pathological mechanism. Our previous work identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) which are associated with winter SAD, but whether and how these variants lead to the disorder remain to be characterized. Here we found that mice carrying humanPER3-P415A/H417R display increased depression-like behaviors under short winter-like days. Light exerts bi-directional effects via two distinct pathways that converge on the rate-limiting enzyme of serotonin synthesis pathway, tryptophan hydroxylase 2 (TPH2). On one hand, light up-regulates TPH2 level in the dorsal raphe nucleus (DR), a major serotonergic center in the brain, via activation of ventral lateral geniculate nucleus which receives direct retinal inputs and sends projections to DR. On the other hand, light down-regulates DR TPH2 level by activating the hypothalamic-pituitary-adrenal axis which results in increased corticosterone that represses Tph2 transcription. These two pathways maintain serotonergic homeostasis under different day length, while PER3-P415A/H417R tips the balance under short days by acting in the adrenal gland and enhancing corticosterone synthesis, leading to winter-depression like phenotypes. 

Biography：

张珞颖，2003年本科毕业于北京大学生物科学专业，2009年博士毕业于美国西北大学神经科学专业，2010-2014年于美国加州大学旧金山分校神经内科系Ying-Hui Fu与Louis Ptacek院士实验室从事博士后研究。2015年加入华中科技大学生命科学与技术学院，现为该院教授、生物科学系系主任。在果蝇、小鼠及人的生物钟调节机制等领域取得了一系列成果，在EMBO J、Nature Communications、PNAS等国际权威期刊共发表学术论文20余篇。目前主要研究方向为睡眠与生物钟，包括：（1）研究睡眠和生物钟对情绪的影响及调节机理，从而探索睡眠和生物钟的功能；（2）从系统生物学的角度研究睡眠与生物钟的调控机理和功能。目前任国际生物节律研究会教育委员会委员、中国细胞生物学学会生物节律分会会长。2020年获得国家自然科学基金优秀青年基金的支持。