TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway
Abstract Background Autism spectrum disorder (ASD) encompasses a diverse range of neurodevelopmental disorders, but the precise underlying pathogenesis remains elusive. This study aim to explore the potential mechanism of TREM2 in regulating microglia function in ASD. Materials and methods The offsp...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Molecular Brain |
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| Online Access: | https://doi.org/10.1186/s13041-024-01081-x |
| _version_ | 1827325762741469184 |
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| author | Yi Tian Xiao Xiao Weiliang Liu Shanqing Cheng Na Qian Ling Wang Yang Liu Rong Ai Xiaoping Zhu |
| author_facet | Yi Tian Xiao Xiao Weiliang Liu Shanqing Cheng Na Qian Ling Wang Yang Liu Rong Ai Xiaoping Zhu |
| author_sort | Yi Tian |
| collection | DOAJ |
| description | Abstract Background Autism spectrum disorder (ASD) encompasses a diverse range of neurodevelopmental disorders, but the precise underlying pathogenesis remains elusive. This study aim to explore the potential mechanism of TREM2 in regulating microglia function in ASD. Materials and methods The offspring rat model of ASD was established through prenatal exposure to valproic acid (VPA), and the behavioral symptoms of the ASD model were observed. On postnatal day (PND) 7 and PND 28, the effects of prenatally exposure to VPA on synaptic development and microglia phenotype of offspring rats were observed. Primary microglia were cultured in vitro. Lentivirus and adenovirus were utilized to interfere with TREM2 and overexpress TREM2. Results Prenatally VPA exposure induced offspring rats to show typical ASD core symptoms, which led to abnormal expression of synapse-related proteins in the prefrontal cortex of offspring rats, changed the phenotype of microglia in offspring rats, promoted the polarization of microglia to pro-inflammatory type, and increased inflammatory response. The experimental results in vitro showed that overexpression of TREM2 could increase the expression of Gephyrin, decrease the content of CD86 protein and increase the content of CD206 protein. In addition, after the expression of TREM2 was interfered, the content of p-P38 MAPK protein increased and the content of p-ELK-1 protein decreased. Conclusion The protective influence of TREM2 on the VPA-induced ASD model is attributed to its inhibition of the P38 MAPK pathway, this protective effect may be achieved by promoting the polarization of microglia to anti-inflammatory phenotype and improving the neuronal synaptic development. |
| first_indexed | 2024-03-07T14:34:01Z |
| format | Article |
| id | doaj.art-7a826b1cbf2e4f079417e2edf65d4e6f |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-03-07T14:34:01Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-7a826b1cbf2e4f079417e2edf65d4e6f2024-03-05T20:44:35ZengBMCMolecular Brain1756-66062024-02-0117111210.1186/s13041-024-01081-xTREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathwayYi Tian0Xiao Xiao1Weiliang Liu2Shanqing Cheng3Na Qian4Ling Wang5Yang Liu6Rong Ai7Xiaoping Zhu8School of Pediatrics, Guizhou Medical UniversitySchool of Pediatrics, Guizhou Medical UniversitySchool of Pediatrics, Guizhou Medical UniversitySchool of Pediatrics, Guizhou Medical UniversitySchool of Pediatrics, Guizhou Medical UniversitySchool of Pediatrics, Guizhou Medical UniversitySchool of Pediatrics, Guizhou Medical UniversitySchool of Pediatrics, Guizhou Medical UniversitySchool of Pediatrics, Guizhou Medical UniversityAbstract Background Autism spectrum disorder (ASD) encompasses a diverse range of neurodevelopmental disorders, but the precise underlying pathogenesis remains elusive. This study aim to explore the potential mechanism of TREM2 in regulating microglia function in ASD. Materials and methods The offspring rat model of ASD was established through prenatal exposure to valproic acid (VPA), and the behavioral symptoms of the ASD model were observed. On postnatal day (PND) 7 and PND 28, the effects of prenatally exposure to VPA on synaptic development and microglia phenotype of offspring rats were observed. Primary microglia were cultured in vitro. Lentivirus and adenovirus were utilized to interfere with TREM2 and overexpress TREM2. Results Prenatally VPA exposure induced offspring rats to show typical ASD core symptoms, which led to abnormal expression of synapse-related proteins in the prefrontal cortex of offspring rats, changed the phenotype of microglia in offspring rats, promoted the polarization of microglia to pro-inflammatory type, and increased inflammatory response. The experimental results in vitro showed that overexpression of TREM2 could increase the expression of Gephyrin, decrease the content of CD86 protein and increase the content of CD206 protein. In addition, after the expression of TREM2 was interfered, the content of p-P38 MAPK protein increased and the content of p-ELK-1 protein decreased. Conclusion The protective influence of TREM2 on the VPA-induced ASD model is attributed to its inhibition of the P38 MAPK pathway, this protective effect may be achieved by promoting the polarization of microglia to anti-inflammatory phenotype and improving the neuronal synaptic development.https://doi.org/10.1186/s13041-024-01081-xAutism spectrum disorderTriggering receptor expressed on myeloid cells-2Microglial cellsSynapticValproic acidP38 MAPK pathway |
| spellingShingle | Yi Tian Xiao Xiao Weiliang Liu Shanqing Cheng Na Qian Ling Wang Yang Liu Rong Ai Xiaoping Zhu TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway Molecular Brain Autism spectrum disorder Triggering receptor expressed on myeloid cells-2 Microglial cells Synaptic Valproic acid P38 MAPK pathway |
| title | TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway |
| title_full | TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway |
| title_fullStr | TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway |
| title_full_unstemmed | TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway |
| title_short | TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway |
| title_sort | trem2 improves microglia function and synaptic development in autism spectrum disorders by regulating p38 mapk signaling pathway |
| topic | Autism spectrum disorder Triggering receptor expressed on myeloid cells-2 Microglial cells Synaptic Valproic acid P38 MAPK pathway |
| url | https://doi.org/10.1186/s13041-024-01081-x |
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