GPR17 modulates anxiety-like behaviors <i>via</i> basolateral amygdala to ventral hippocampal CA1 glutamatergic projection.

Ruizhe NIE; Xinting ZHOU; Jiaru FU; Shanshan HU; Qilu ZHANG; Weikai JIANG; Yizi YAN; Xian CAO; Danhua YUAN; Yan LONG; Hao HONG; Susu TANG

Return

GPR17 modulates anxiety-like behaviors via basolateral amygdala to ventral hippocampal CA1 glutamatergic projection.

Author: Ruizhe NIE ¹ ; Xinting ZHOU ¹ ; Jiaru FU ¹ ; Shanshan HU ¹ ; Qilu ZHANG ¹ ; Weikai JIANG ¹ ; Yizi YAN ¹ ; Xian CAO ¹ ; Danhua YUAN ¹ ; Yan LONG ¹ ; Hao HONG ¹ ; Susu TANG ¹
Author Information

1. Department of Pharmacology, College of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Publication Type:Journal Article
Keywords: Anxiety; Basolateral amygdala; CRS; Cangrelor; GPR17; Glutamatergic neurons; Glutamatergic projection; Ventral hippocampal CA1
From: Acta Pharmaceutica Sinica B 2024;14(11):4789-4805
CountryChina
Language:English
Abstract: Anxiety disorders are one of the most epidemic and chronic psychiatric disorders. An incomplete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders. GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders. However, no study has investigated the role of GPR17 in psychiatric disorders. In a well-established chronic restraint stress (CRS) mouse model, using a combination of pharmacological and molecular biology techniques, viral tracing, in vitro electrophysiology recordings, in vivo fiber photometry, chemogenetic manipulations and behavioral tests, we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala (BLA) glutamatergic neurons. Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutamatergic neurons effectively improved anxiety-like behaviors. Overexpression of GPR17 in BLA glutamatergic neurons increased the susceptibility to anxiety-like behaviors. What's more, BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CA1 glutamatergic projection. Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders.