Maternal Immune Activation Induces Neuroinflammation and Cortical Synaptic Deficits in the Adolescent Rat Offspring

International Journal of Molecular Sciences

Agata Adamczyk¹  RobertK. Filipkowski²  Rafał Polowy²  Agnieszka Dominiak³  GraceY. Sun⁴  Magdalena Gąssowska-Dobrowolska⁵  GrzegorzA. Czapski⁵  Anna Wilkaniec⁵  Aleksandra Zawadzka⁵  Magdalena Cieślik⁵  Henryk Jęśko⁵  DavidQ. Beversdorf⁶  Magdalena Gewartowska⁷  Małgorzata Frontczak-Baniewicz⁷  PawełM. Boguszewski⁸ 

[1] Neurology, and Psychological Sciences, William and Nancy Thompson Endowed Chair in Radiology, DC069.10, One Hospital Drive, University of Missouri, Columbia, MO 65211, USA;Behavior and Metabolism Research Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland;Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, Żwirki i Wigury 61, 02-097 Warsaw, Poland;Department of Biochemistry, University of Missouri, 117 Schweitzer Hall, Columbia, MO 65201, USA;Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland;Departments of Radiology;Electron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland;Laboratory of Animal Models, Neurobiology Center, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteur 3, 02-093 Warsaw, Poland;

关键词: maternal immune activation;    lipopolysaccharide;    synaptic proteins;    autism;   

DOI  :  10.3390/ijms21114097

来源: DOAJ

【 摘 要 】

Maternal immune activation (MIA), induced by infection during pregnancy, is an important risk factor for neuro-developmental disorders, such as autism. Abnormal maternal cytokine signaling may affect fetal brain development and contribute to neurobiological and behavioral changes in the offspring. Here, we examined the effect of lipopolysaccharide-induced MIA on neuro-inflammatory changes, as well as synaptic morphology and key synaptic protein level in cerebral cortex of adolescent male rat offspring. Adolescent MIA offspring showed elevated blood cytokine levels, microglial activation, increased pro-inflammatory cytokines expression and increased oxidative stress in the cerebral cortex. Moreover, pathological changes in synaptic ultrastructure of MIA offspring was detected, along with presynaptic protein deficits and down-regulation of postsynaptic scaffolding proteins. Consequently, ability to unveil MIA-induced long-term alterations in synapses structure and protein level may have consequences on postnatal behavioral changes, associated with, and predisposed to, the development of neuropsychiatric disorders.

【 授权许可】

Unknown