• Neuroscience · Nov 2022

    Increased anxiety-like behaviors in Adgra1-/- male but not female mice are attributable to elevated neuron dendritic density, upregulated PSD95 expression, and abnormal activation of the PI3K/AKT/GSK-3β and MEK/ERK pathways.

    • Xiao-Hong Zhang, Chun-Ling Shen, Xi-Yi Wang, Wen-Feng Xiong, Xuan Shang, Ling-Yun Tang, Hong-Xin Zhang, Ying-Han Wan, You-Bing Wu, Jian Fei, Qi-Zhong Yi, and Zhu-Gang Wang.
    • State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200025, China. Electronic address: zhangxh71129@163.com.
    • Neuroscience. 2022 Nov 1; 503: 131145131-145.

    AbstractAdhesion G protein-coupled receptor A1 (ADGRA1) belongs to the G protein-coupled receptor (GPCR) family, and its physiological function remains largely unknown. We found that Adgra1 is highly and exclusively expressed in the brain, suggesting that Adgra1 may be involved in the regulation of neurological behaviors including anxiety, depression, learning and memory. To this end, we comprehensively analyzed the potential role of ADGRA1 in the neurobehaviors of mice by comparing Adgra1-/- and their wild-type (wt) littermates. We found that Adgra1-/- male but not female mice exhibited elevated anxiety levels in the open field, elevated plus maze, and light-dark box tests, with normal depression levels in the tail-suspension and forced-swim tests, and comparable learning and memory abilities in the Morris water maze, Y maze, fear condition, and step-down avoidance tests. Further studies showed that ADGRA1 deficiency resulted in higher dendritic branching complexity and spine density as evidenced by elevated expression levels of SYN and PSD95 in amygdalae of male mice. Finally, we found that PI3K/AKT/GSK-3β and MEK/ERK in amygdalae of Adgra1-deficient male mice were aberrantly activated when compared to wt male mice. Together, our findings reveal an important suppressive role of ADGRA1 in anxiety control and synaptic function by regulating the PI3K/AKT/GSK-3β and MEK/ERK pathways in amygdalae of male mice, implicating a potential, therapeutic application in novel anti-anxiety drug development.Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

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