Induction of Anxiety-Like Phenotypes by Knockdown of Cannabinoid Type-1 Receptors in the Amygdala of Marmosets

Lin Zhu ¹Di Zheng ²Rui Li ¹Chen-Jie Shen ³Ruolan Cai ¹Chenfei Lyu ¹Binliang Tang ⁴Hao Sun ¹Xiaohui Wang ¹Yu Ding ²Bin Xu ⁵Guoqiang Jia ¹Xinjian Li ¹Lixia Gao ¹Xiao-Ming Li⁶

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作者信息

1. Department of Neurobiology and Department of Neurology of Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China;NHC and CAMS Key Laboratory of Medical Neurobiology,MOE Frontier Science Center for Brain Research and Brain-Machine Integration,School of Brain Science and Brian Medicine,Zhejiang University,Hangzhou 310058,China;Interdisciplinary Institute of Neuroscience and Technology,Zhejiang University School of Medicine,Hangzhou 310029,China
2. Department of Neurobiology and Department of Neurology of Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China;NHC and CAMS Key Laboratory of Medical Neurobiology,MOE Frontier Science Center for Brain Research and Brain-Machine Integration,School of Brain Science and Brian Medicine,Zhejiang University,Hangzhou 310058,China
3. NHC and CAMS Key Laboratory of Medical Neurobiology,MOE Frontier Science Center for Brain Research and Brain-Machine Integration,School of Brain Science and Brian Medicine,Zhejiang University,Hangzhou 310058,China
4. Interdisciplinary Institute of Neuroscience and Technology,Zhejiang University School of Medicine,Hangzhou 310029,China;Rehabilitation Medicine Center, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 311399, China
5. Interdisciplinary Institute of Neuroscience and Technology,Zhejiang University School of Medicine,Hangzhou 310029,China
6. Department of Neurobiology and Department of Neurology of Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China;NHC and CAMS Key Laboratory of Medical Neurobiology,MOE Frontier Science Center for Brain Research and Brain-Machine Integration,School of Brain Science and Brian Medicine,Zhejiang University,Hangzhou 310058,China;Center for Brain Science and Brain-Inspired Intelligence, Research Units for Emotion and Emotion Disorders, Chinese Academy of Medical Sciences, China/G
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Abstract

The amygdala is an important hub for regulating emotions and is involved in the pathophysiology of many mental diseases,such as depression and anxiety.Meanwhile,the endocannabinoid system plays a crucial role in regu-lating emotions and mainly functions through the cannabi-noid type-1 receptor(CB1R),which is strongly expressed in the amygdala of non-human primates(NHPs).However,it remains largely unknown how the CB1Rs in the amyg-dala of NHPs regulate mental diseases.Here,we investi-gated the role of CB1R by knocking down the cannabinoid receptor 1(CNR1)gene encoding CB1R in the amygdala of adult marmosets through regional delivery of AAV-SaCas9-gRNA.We found that CB1R knockdown in the amygdala induced anxiety-like behaviors,including disrupted night sleep,agitated psychomotor activity in new environments,and reduced social desire.Moreover,marmosets with CB1R-knockdown had up-regulated plasma cortisol levels.These results indicate that the knockdown of CB1Rs in the amygdala induces anxiety-like behaviors in marmosets,and this may be the mechanism underlying the regulation of anxiety by CB1Rs in the amygdala of NHPs.

Key words

Cannabinoid type-1 receptor/Amygdala/Marmoset/Anxiety/CRISPR/Cas9

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基金项目

Zhejiang Province Natural science Foundation of China(LD22H090003)

Key-Area Research and Development Program of Guangdong Province(2019B030335001)

Key-Area Research and Development Program of Guangdong Province(2018B030334001)

National Natural Science Foundation of China(31871070)

National Natural Science Foundation of China(82090031)

National Natural Science Foundation of China(32071097)

National Natural Science Foundation of China(31871056)

National Natural Science Foundation of China(32170991)

Key R&D Program of Zhejiang Province(2020C03009)

Fundamental Research Funds for the Central Universities(2021FZZX001-37)

CAMS Innovation Fund for Medical Sciences(2019-I2M-5-057)

出版年

2023

神经科学通报(英文版)

中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD

影响因子：0.741

ISSN：1673-7067

参考文献量67

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