Abstract:

Pregnancy comes with a combination of physical changes and physiological immunosuppression that increases the susceptibility of women to pathogens and in turn, rises the prevalence of infectious diseases. During this period, the fetal brain is particularly sensitive to internal and external signals that define and guide its development. However, immunosuppression during pregnancy also represents a vulnerable stage in which the combination of molecular signals expressed at specific stages of fetal maturation can result in deficient brain development, a phenomenon poorly understood despite being connected with the risk of developing psychiatric disorders (Knuesel et al., 2014). Strikingly, a potentially harmful signal associated with abnormal brain development in the offspring is the maternal production of cytokines to counteract infectious diseases. Studies have documented that maternal cytokines can cross the placental barrier and influence fetal brain development. This physiological response, also called maternal immune activation (MIA), represents a risk factor for long-lasting alterations in brain development, neuronal activity, and behavioral deficits (for a comprehensive review, see (Estes and McAllister, 2016)). Maternal synthesis and release of pro-inflammatory cytokines, including interleukin 1β, interleukin 6, tumor necrosis factor α, and several interferons, such as interferon-α, in response to environmental insults such as viral or bacterial infections, are associated with dysregulated neuronal physiology and behavioral abnormalities in the offspring. In fact, several psychiatric disorders, among them autism spectrum disorder and schizophrenia, have been postulated to have at least an intrauterine or early-life component associated with viral infections (Atladóttir et al., 2010) and MIA (Vlasova et al., 2021).