Impact of maternal immune activation on dendritic spine development

Abstract

Dendritic spines are small dendritic protrusions that harbor most excitatory synapses in the brain. The proper generation and maturation of dendritic spines are crucial for the regulation of synaptic transmission and formation of neuronal circuits.Abnormalities in dendritic spine density and morphology are common pathologies in autism and schizophrenia. According to epidemiological studies, one risk factor for these neurodevelopmental disorders is maternal infection during pregnancy. This review discusses spine alterations in animal models of maternal immune activation in the context of neurodevelopmental disorders. We describe potential mechanisms that might be responsible for prenatal infection-induced changes in the dendritic spine phenotype and behavior in offspring.

Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS

“…Environmental risk factors that may, in concert, affect pruning [218][219][220][221][222][223] include maternal infection 223,[225][226][227][228] , obstetric complications and maternal diet 229,230 in utero and pollution, infection and early life stress later during early life development. Adapted from reF.…”

Interferon-γ exposure of human iPSC-derived neurons alters major histocompatibility complex I and synapsin protein expression

“…Although there are many plausible factors that are critical for establishing neurodevelopmental resilience or susceptibility to MIA ( 2 ), there is evidence to suggest that the intensity of the maternal immune response is one important factor linking maternal infection to the potential for differential brain development and behavioral phenotypes ( 3 – 5 ). Indeed, animal MIA models display deficits in cognitive and social behaviors ( 6 ), which are accompanied by altered synaptic plasticity, decreased synaptic protein levels, and reduced dendritic spine density, predominantly in the prefrontal cortex and hippocampus ( 7 – 11 ). These findings are consistent with in vivo neuroimaging evidence for reduced synaptic density, as measured by reduced binding of positron emission tomography (PET) radioligands targeting synaptic vesicle glycoprotein 2A (SV2A) in schizophrenia ( 12 , 13 ), reduced dendritic spines ( 14 ), and a meta-analysis confirming decreased expression of synaptic proteins in post-mortem brain tissue from individuals with schizophrenia ( 15 ).…”

Prefrontal Cortex Response to Prenatal Insult and Postnatal Opioid Exposure

“…The consistency between the MIA and morphine effects detected in the present study and those reported for other brain regions may be related to the prefrontal cortex neurons that project into the amygdala and forward to the hippocampus and back to the prefrontal cortex [ 40 ]. Moreover, the role of cell adhesion molecules in the context of MIA and ASD has been reviewed and synaptic cell adhesion molecules are well-characterized ASD risk genes [ 41 ].…”