IMR Press / JIN / Volume 22 / Issue 6 / DOI: 10.31083/j.jin2206154
Open Access Original Research
Astrocyte-Ablation of Mtnr1b Increases Anxiety-Like Behavior in Adult Male Mice
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1 Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, 400015 Chongqing,Β China
2 The Second Affiliated Hospital and Yuying Children's Hospital, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Mental Disorders, School of Mental Health and Wenzhou Kangning Hospital, Institute of Aging, Wenzhou Medical University, 325035 Wenzhou, Zhejiang,Β China
3 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), 325001 Wenzhou, Zhejiang,Β China
*Correspondence: (Weihui Zhou); (Weihong Song)
J. Integr. Neurosci. 2023, 22(6), 154;
Submitted: 14 August 2023 | Revised: 9 September 2023 | Accepted: 15 September 2023 | Published: 30 October 2023
Copyright: Β© 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Astrocytes are essential for synaptic transmission, and their dysfunction can result in neuropsychiatric disorders such as anxiety and depression. Many studies have shown that global knockout of Melatonin receptor 2 (Mtnr1b) is associated with the development of various mental disorders. Aim: This study aimed to investigate the effects of astrocyte ablation of Mtnr1b on cognitive function and anxiety-like behavior in mice, as well as the potential biological mechanisms. Methods: A conditional Cre-loxP system allowing deletion of Mtnr1b from astrocytes was developed to investigate the specific role Mtnr1b. Control and Mtnr1b cKOπΊπ‘“π‘Žπ‘ mice were selected for cognitive function behavioral testing (Morris water maze test, novel object recognition test) and emotion-related behavioral testing (open field, elevated plus maze). After testing, brain tissue was collected and examined by immunofluorescence for the expression of neuronal nuclei (NeuN), glutamate decarboxylase 67 (GAD67), and vesicular glutamate transporter 1 (vGluT1). RNA-seq was performed on hippocampal tissue from control and Mtnr1b cKOπΊπ‘“π‘Žπ‘ mice to identify differentially expressed genes. Additional confirmation of differential gene expression was performed using real-time quantitative polymerase chain reaction (qRT-PCR). Results: Mtnr1b cKOπΊπ‘“π‘Žπ‘ mice were not significantly different from control mice in the Morris water maze and novel object recognition tests. Results from the open field and elevated plus maze tests showed that Mtnr1b cKOπΊπ‘“π‘Žπ‘ mice exhibited significantly more anxiety-like behavior than did controls. Immunofluorescence revealed that the number of mature neurons did not differ significantly between Mtnr1b cKOπΊπ‘“π‘Žπ‘ mice and controls. The expression of GAD67 in the hippocampal CA1 and CA3 areas of Mtnr1b cKOπΊπ‘“π‘Žπ‘ mice was significantly lower than in the control group, but no significant difference was detected for vGluT1 expression. RNA-seq and qRT-PCR results showed that Mtnr1b knockout in astrocytes led to a decrease in the levels of gamma-aminobutyric acid sub-type A (GABAA) receptors and Kir2.2. Conclusions: The astrocyte-specific knockout in Mtnr1b cKOπΊπ‘“π‘Žπ‘ mice results in anxiety-like behavior, which is caused by down-regulation of gamma-aminobutyric acid-ergic (GABAergic) synaptic function.

melatonin receptor 2
Key Laboratory of Alzheimer’s Disease of Zhejiang Province
Zhejiang Provincial Clinical Research Center for Mental Disorders (WS)
Fig. 1.
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