C1ql3 knockout affects microglia activation, neuronal integrity, and spontaneous behavior in Wistar rats  

作　　者：Li Zhang Wei Dong Jingwen Li Shan Gao Hanxuan Sheng Qi Kong Feifei Guan Lianfeng Zhang 

机构地区：[1]Beijing Engineering Research Center for Experimental Animal Models of Human Diseases,Institute of Laboratory Animal Science,Peking Union Medicine College,Chinese Academy of Medical Sciences,Beijing,China [2]Key Laboratory of Human Disease Comparative Medicine,National Health Commission of China(NHC),Institute of Laboratory Animal Science,Peking Union Medicine College,Chinese Academy of Medical Sciences,Beijing,China [3]Neuroscience Center,Chinese Academy of Medical Sciences,Beijing,China

出　　处：《Animal Models and Experimental Medicine》2025年第2期332-343,共12页动物模型与实验医学(英文)

基　　金：The present work was supported by the National Natural Science Foundation(31970508);the National Key Research and Development Program of China(2022YFF0710702).

摘　　要：Background:C1QL3 is widely expressed in the brain and is specifically produced by a subset of excitatory neurons.However,its function is still not clear.We established C1ql3-deficient rats to investigate the role of C1QL3 in the brain.Methods:C1ql3 knockout(KO)rats were generated using CRISPR/Cas9.C1ql3 KO was determined by polymerase chain reaction(PCR),DNA sequencing,and western blot-ting.Microglia morphology and cytokine expression with or without lipopolysaccha-ride(LPS)stimulus were analyzed using immunohistochemistry and real-time PCR.The brain structure changes in KO rats were examined using magnetic resonance imaging.Neuronal architecture alteration was analyzed by performing Golgi staining.Behavior was evaluated using the open field test,Morris water maze test,and Y maze test.Results:C1ql3 KO significantly increased the number of ramified microglia and decreased the number of hypertrophic microglia,whereas C1ql3 KO did not in-fluence the expression of pro-inflammatory factors and anti-inflammatory factors except IL-10.C1ql3 KO brains had more amoeboid microglia types and higher Arg-1 expression compared with the WT rats after LPS stimulation.The brain weights and HPC sizes of C1ql3 KO rats did not differ from WT rats.C1ql3 KO damaged neuronal integrity including neuron dendritic arbors and spine density.C1ql3 KO rats demonstrated an increase in spontaneous activity and an impairment in short working memory.Conclusions:C1ql3 KO not only interrupts the neuronal integrity but also affects the microglial activation,resulting in hyperactive behavior and impaired short memory in rats,which highlights the role of C1QL3 in the regulation of structure and function of both neuronal and microglial cells.

关 键 词：C1QL3 KNOCKOUT MICROGLIA NEURON rat 

分 类 号：R74[医药卫生—神经病学与精神病学]