Maternal Immune Activation Induces Neuroinflammation and Cortical Synaptic Deficits in the Adolescent Rat Offspring
Magdalena Cieślik1, Magdalena Gąssowska-Dobrowolska1, Henryk Jęśko1
1Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland.
Insights
Maternal immune activation during pregnancy alters offspring brain development, leading to neuroinflammation and synaptic deficits. These changes may predispose offspring to long-term neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Maternal immune activation (MIA) is a significant risk factor for neurodevelopmental disorders like autism.
- Altered maternal cytokine signaling can impact fetal brain development, leading to neurobiological and behavioral changes in offspring.
Purpose of the Study:
- To investigate the effects of lipopolysaccharide-induced MIA on neuroinflammation, synaptic morphology, and protein levels in the cerebral cortex of adolescent male rats.
Main Methods:
- Induction of MIA using lipopolysaccharide in pregnant rats.
- Analysis of blood cytokine levels, microglial activation, pro-inflammatory cytokine expression, and oxidative stress in offspring cerebral cortex.
- Assessment of synaptic ultrastructure and key synaptic protein levels (presynaptic and postsynaptic).
Main Results:
- MIA offspring exhibited elevated blood cytokines, heightened microglial activation, increased pro-inflammatory cytokine expression, and elevated oxidative stress in the cerebral cortex.
- Pathological alterations in synaptic ultrastructure were observed in MIA offspring.
- Deficits in presynaptic proteins and downregulation of postsynaptic scaffolding proteins were identified in MIA offspring.
Conclusions:
- MIA induces significant long-term neuroinflammatory and synaptic changes in the developing brain.
- These synaptic alterations, including protein deficits, may contribute to postnatal behavioral changes and increase susceptibility to neuropsychiatric disorders.
Abstract:
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.
