我们实验室的研究方向集中在两个方面：第一个是抑郁症发病的应激环路机制。体内应激反应的水平由下丘脑-垂体-肾上腺轴（HPA轴）的活性决定， 而下丘脑促肾上腺皮质激素释放激素（CRH）神经元则是调节HPA轴活性的中枢驱动力。我们重点研究了抑郁症患者和抑郁症模型动物下丘脑本身CRH神经元活性改变、以及高位中枢对下丘脑CRH神经元活性的调控机制。第二个方向是阿尔茨海默病（AD）发病的神经内分泌机制和早期诊治。我们从AD患者下丘脑神经内分泌细胞自身活性改变以及神经内分泌激素对于AD相关病理改变之间的关系两方面展开研究。我们研究的特色是以病人脑中的病理发现为切入点，开展原创性的研究工作，目的在于为抑郁症或AD的诊断和治疗寻找可能的方法和靶点。我们在人脑的工作是与荷兰脑库以及荷兰神经科学研究所的Swaab教授合作进行的。

抑郁症的发病应激环路机制 

提出并证实抑郁症发病中多组配对激素受体调控下丘脑CRH神经元的作用方式及机制。在单细胞分辨率水平绘制了小鼠的CRH全脑分布图谱，在跨单突触层次揭示了下丘脑和杏仁核CRH神经元的输入和输出神经环路，发现前额叶CRH神经元在面对应激刺激时可促进机体采取主动应对行为。上述发现揭示了脑内CRH神经环路除参与经典的HPA轴的活性调控外，还在应激应对策略选择、恐惧和焦虑反应中发挥重要作用，并在抑郁症等应激相关疾病的发生和发展中发挥重要作用。

AD发病的神经内分泌机制和早期诊治 

AD患者昼夜节律行为紊乱的结构基础：睡眠-觉醒节律紊乱是影响AD患者生活质量和认知功能的严重问题。我们的研究发现AD患者脑的生物钟即视交叉上核的退行性改变是其节律紊乱的结构基础，脑脊液松果体素的水平下降与其病理改变密切相关并且是AD病程中的早期事件。有关发现促进了光治疗结合松果体素替代治疗改善AD患者昼夜节律紊乱的临床应用。用于AD早期诊断的分子影像探针：淀粉样蛋白沉积所形成的老年斑是AD病理诊断的金标准之一。我们研发了靶向脑内淀粉样蛋白的分子探针。实现了AD动物的在体无创性近红外成像，可以动态监测脑内淀粉样蛋白沉积的状态。关于“用于淀粉样蛋白显像的血管肽及其衍生物”的发明，于2019年和2020年分别获中国、美国和欧洲发明证书。

Chen P, Lou S, Huang Z, Wang Z, Shan QH, Wang Y, Yang Y, Li X, Gong H, Jin Y, Zhang Z and  Zhou JN*. Prefrontal cortex corticotropin-releasing factor neurons motivate behavioral coping strategies during various challenging situations. Neuron 2020 Feb 5. pii: S0896-6273(20)30060-X.

Hu P, van Dam AM, Wang Y, Lucassen PJ, Zhou JN*, 2020. Retinoic acid and depressive disorders: Evidence and possible neurobiological mechanisms. Neurosci Biobehav Rev. 2020 Feb 15;112:376-391.

Wang CW, Nan DD, Wang XM, Ke JZ, Chen GJ, Zhou JN*.2017. A peptide-based near-infrared fluorescence probe for dynamic monitoring senile plaques in Alzheimer’s disease mouse model. Science Bulletin 2017. 62(23):1593-1601.

Zhou JN and Ni RJ., 2016 The Tree Shrew (Tupaia belangeri chinensis) Brain in Stereotaxic Coordinates. Science Press & Springer, 588 pages.

Liu YJ, Meng FT, Wang LL, Zhang LF, Cheng XP, Zhou JN*.2012. Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells. J Pineal Res. 52(4):397-402.

Chen XN, Meng QY, Bao AM, Swaab DF, Wang GH, Zhou JN*.2009. The involvement of retinoic acid receptor-alpha in corticotropin-releasing hormone gene expression and affective disorders. Biol Psychiatry. 66(9):832-9.

Wang SS, Willem K, Inge H, Zhou JN*, Swaab DF. 2008. Gene Expression Analysis in the Human Hypothalamus in Depression by Laser Micro-Dissection and Real Time PCR: the presence of multiple receptor imbalances. Molecular Psychiatry. 13(8):786-99.

Liu YJ, Zhuang J, Zhu HY, Shen YX, Tan ZL, Zhou JN. 2007*. Cultured rat cortical astrocytes synthesize melatonin: absence of a diurnal rhythm. J Pineal Res. 43(3):232-8.

Zhu DF, Wang ZX, Zhang DR, Pan ZL, He S, Hu XP, Chen XC, Zhou JN*. 2006. fMRI revealed neural substrate for reversible working memory dysfunction in subclinical hypothyroidism. Brain. 129(11):2923-30.

Bao AM, Hestiantoro A, Van Someren EJ, Swaab DF, Zhou JN*. 2005. Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders. Brain. 128(6):1301-13.

Qin S, Hu XY, Xu H, Zhou JN*. 2004. Regional alteration of synapsin I in the hippocampal formation of Alzheimer's disease patients. Acta Neuropathol. 107(3):209-15.

Zhou JN*, Liu RY, Willem K, Hofman MA, Swaab DF. 2003. Early neuropathological Alzheimer's changes in aged individuals are accompanied by decreased cerebrospinal fluid melatonin levels. J Pineal Res. 35(2):125-30.

 Hu XY, Qin S, Lu YP, Ravid R, Swaab DF, Zhou JN*. 2003. Decreased estrogen receptor-alpha expression in hippocampal neurons in relation to hyperphosphorylated tau in Alzheimer patients. Acta Neuropathol. 106(3):213-20.

Zhou JN*, Liu RY, van Heerikhuize J, Hofman MA, Swaab DF. 2003. Alterations in the circadian rhythm of salivary melatonin begin during middle-age. J Pineal Res. 34(1):11-6.

Zhou JN, Riemersma RF, Unmehopa UA, Hoogendijk WJ, van Heerikhuize JJ, Hofman MA, Swaab DF*. 2001. Alterations in arginine vasopressin neurons in the suprachiasmatic nucleus in depression. Arch Gen Psychiatry. 58(7):655-62.