Maternal immune activation generates anxiety in offspring: A translational meta-analysis

Abstract

Maternal immune activation (MIA) during pregnancy is recognized as an etiological risk factor for various psychiatric disorders, such as schizophrenia, major depressive disorder, and autism. Prenatal immune challenge may serve as a “disease primer” for alteration of the trajectory of fetal brain development that, in combination with other genetic and environmental factors, may ultimately result in the emergence of different psychiatric conditions. However, the association between MIA and an offspring’s chance of developing anxiety disorders is less clear. To evaluate the effect of MIA on offspring anxiety, a systematic review and meta-analysis of the preclinical literature was conducted. We performed a systematic search of the PubMed, Web of Science, PsycINFO, and Cochrane Library electronic databases using the PRISMA and World Health Organization (WHO) methodologies for systematic reviews. Studies that investigated whether MIA during pregnancy could cause anxiety symptoms in rodent offspring were included. Overall, the meta-analysis showed that MIA induced anxiety behavior in offspring. The studies provide strong evidence that prenatal immune activation impacts specific molecular targets and synapse formation and function and induces an imbalance in neurotransmission that could be related to the generation of anxiety in offspring. Future research should further explore the role of MIA in anxiety endophenotypes. According to this meta-analysis, MIA plays an important role in the pathophysiological mechanisms of anxiety disorders and is a promising therapeutic target.

Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

“…Importantly, recent evidence shows that hRSV can infect placental cells, cross the placental barrier, and, therein, be vertically transmitted to the fetus [18,24,40]. One of the unknown relevant issues is the MIA effect on hRSV infection, which is essential since MIA has been associated with cognitive and behavioral impairment and neuropsychiatric illnesses such as SCZ and ASD [32,53,57,94]. The critical information about the harmful effect of MIA on the neurodevelopment of the fetus with neurological consequences in adulthood came from the Poly: IC model, which provides valuable evidence of the alteration of neurotransmitters pathways and cytokines expression that affect brain development [95,96].…”

“…During pregnancy, the viral infection promotes MIA, which has been associated with alterations in the neurodevelopment of the fetus, such as cognitive impairment and neuropsychiatric illness [48][49][50]. Several studies using pregnant animal model exposure to polyriboinosinic-polyribocytidylic acid (Poly: IC) show detrimental effects on the brain of the fetus development, promoting neurological outcomes in adulthood [32,48,[51][52][53]. It has been observed that the Poly: IC treatment in animals during pregnancy promote alterations in the neurotransmitters signaling such as dopamine (DA), γ-aminobutyric acid (GABA), and serotonin (5-HT) at different gestational stages [54][55][56][57].…”

Transcriptomic underpinnings of high and low mirror aggression zebrafish behaviours

“…Anxiety has also been linked to changes within the immune system, which is interesting in the current context, given that HAZ are less anxious than LAZ. For example, a recent study in mice showed that IL-17a secreted from meningeal γδ17 T cells expressing high levels of chemokine receptor 6 regulates anxiety-like behaviour [ 60 ] and a recent meta-analysis found that maternal immune activation during pregnancy induces anxiety behaviour in offspring [ 61 ]. In line with these findings, LAZ and HAZ show differences in cytokine expression ( il12bb , tnfrsf1b , cxcl12b , ccl35.2 and macrophage expressed 1, tandem duplicate 2 ) chemokine receptor expression ( xcr1a.1 , xcr1b.1 , ccr11.1 and ccr8.1 ) and other genes related to immune system activity ( ptgr1 , ltb4r2b , ltc4s , tlr4ba and toll-like receptor 8a ).…”

Maternal Immune Activation Induced by Prenatal Lipopolysaccharide Exposure Leads to Long-Lasting Autistic-like Social, Cognitive and Immune Alterations in Male Wistar Rats

“…In the last few years, there has been a growing interest in neurodevelopmental disorders (NDDs) related to maternal infections and associated inflammation. Indeed, increasing epidemiological and preclinical studies have provided substantial support to the association between maternal immune activation (MIA) during gestation and an increased susceptibility in the offspring to develop various psychiatric and neurological disorders, including (but not limited to) autism spectrum disorder (ASD) [ 1 , 2 , 3 , 4 , 5 ]. Specifically, several studies explored the correlation between intrauterine infections and altered fetal brain development, resulting in long-term cognitive and behavioral impairments due to the fetal inflammatory response, regardless of the specific pathogen involved [ 6 ].…”