Poly(I:C) Challenge Alters Brain Expression of Oligodendroglia-Related Genes of Adult Progeny in a Mouse Model of Maternal Immune Activation

Zhang, Xiao-Fan1,2; Chen, Ting3,4; Yan, Aifen5; Xiao, Jia6,7; Xie, Yong-Li7; Yuan, Jing7; Chen, Pin6; Wong, Anderson On-Lam8; Zhang, Yang3,4; Wong, Nai-Kei2,7

2020-06-30

10.3389/fnmol.2020.00115

Frontiers in Molecular Neuroscience   影响因子和分区

1662-5099

Background: Altered white matter connectivity, as evidenced by pervasive microstructural changes in myelination and axonal integrity in neuroimaging studies, has been implicated in the development of autism spectrum disorder (ASD) and related neurodevelopmental conditions such as schizophrenia. Despite an increasing appreciation that such white matter disconnectivity is linked to social behavior deficits, virtually no etiologically meaningful myelin-related genes have been identified in oligodendrocytes, the key myelinating cells in the CNS, to furnish an account on the causes. The impact of neurodevelopmental perturbations during pregnancy such as maternal immune activation (MIA) on these genes in memory-related neural networks has not been experimentally scrutinized. Methods: In this study, a mouse model of MIA by the viral dsRNA analog poly(I:C) was employed to mimic the effects of inflammation during pregnancy. Transcriptional expression levels of selected myelin- or oligodendroglia-related genes implicated in schizophrenia or ASD development were analyzed byin situhybridization (ISH) and quantitative real-time PCR (qRT-PCR) with brain samples from MIA and control groups. The analysis focused onSOX-10(SRY-related HMG-box 10),MAG(myelin-associated glycoprotein), andTf(transferrin) expression in the hippocampus and the surrounding memory-related cortical regions in either hemisphere. Results: Specifically, ISH reveals that in the brain of prenatal poly(I:C)-exposed mouse offspring in the MIA model (gestation day 9), mRNA expression of the genesSOX10,MAGandTfwere generally reduced in the limbic system including the hippocampus, retrosplenial cortex and parahippocampal gyrus on either side of the hemispheres. qRT-PCR further confirms the reduction ofSOX10,MAG, andTfexpression in the medial prefrontal cortex, sensory cortex, amygdala, and hippocampus. Conclusions: Our present results provide direct evidence that prenatal exposure to poly(I:C) elicits profound and long-term changes in transcript level and spatial distribution of myelin-related genes in multiple neocortical and limbic regions, notably the hippocampus and its surrounding memory-related neural networks. Our work demonstrates the potential utility of oligodendroglia-related genes as biomarkers for modeling neurodevelopmental disorders, in agreement with the hypothesis that MIA during pregnancy could lead to compromised white matter connectivity in ASD.

maternal immune activation (MIA) poly(I C) SOX10 myelin-associated glycoprotein (MAG) transferrin (Tf) schizophrenia autistic spectrum disorder white matter

SCI

英语

通讯

National Natural Science Foundation of China (NSFC)[81801318] ; National Key R&D Program grant of China[2017YFC1310000] ; Special Support Funds of Shenzhen for Introduced High-Level Medical Team grants[ZDSYS201504301534057][SZSM201512005]

Neurosciences & Neurology

Neurosciences

WOS:000553136300001

FRONTIERS MEDIA SA

Web of Science

1.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Psychiat, Wuhan, Peoples R China
2.Univ Hong Kong, Dept Psychiat, Hong Kong, Peoples R China
3.South China Sea Inst Oceanol, CAS Key Lab Trop Marine Bioresources & Ecol LMB, Key Lab Appl Marine Biol Guangdong Prov, Guangzhou, Peoples R China
4.Chinese Acad Sci, South China Sea Inst Oceanol, Chinese Acad Sci LAMB, Guangzhou, Peoples R China
5.Foshan Univ, Sch Stomatol & Med, Foshan, Peoples R China
6.Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China
7.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis, Hosp Affiliated 2, Shenzhen, Peoples R China
8.Univ Hong Kong, Sch Biol Sci, Hong Kong, Peoples R China

Zhang, Xiao-Fan,Chen, Ting,Yan, Aifen,et al. Poly(I:C) Challenge Alters Brain Expression of Oligodendroglia-Related Genes of Adult Progeny in a Mouse Model of Maternal Immune Activation[J]. Frontiers in Molecular Neuroscience,2020,13.

Zhang, Xiao-Fan.,Chen, Ting.,Yan, Aifen.,Xiao, Jia.,Xie, Yong-Li.,...&Wong, Nai-Kei.(2020).Poly(I:C) Challenge Alters Brain Expression of Oligodendroglia-Related Genes of Adult Progeny in a Mouse Model of Maternal Immune Activation.Frontiers in Molecular Neuroscience,13.

Zhang, Xiao-Fan,et al."Poly(I:C) Challenge Alters Brain Expression of Oligodendroglia-Related Genes of Adult Progeny in a Mouse Model of Maternal Immune Activation".Frontiers in Molecular Neuroscience 13(2020).