Scientists at the Slovak Academy of Sciences reported what they claim is compelling evidence that maternal infections during pregnancy can have lasting effects on offspring brain function. The team investigated the impact of maternal immune activation (MIA) on hippocampal pyramidal neurons in newborn rat offspring and found that prenatal inflammation significantly impaired neuronal excitability. These changes in brain function may underlie the increased risk of neurodevelopmental disorders associated with maternal infections.
“Maternal infections are a known risk factor for conditions like autism, schizophrenia, and depression,” said Eliyahu Dremencov, PhD, corresponding author of the team’s published study in Brain Medicine. “Our research shows that early-life alterations in hippocampal neuron function could be a key mechanism linking prenatal inflammation to these disorders.” Dremencov and colleagues described their findings in a report titled, “Maternal immune activation impairs hippocampal pyramidal neuron excitability in newborn rat offspring: Implications for neurodevelopmental disorders,” in which they concluded, “This study provides novel insights into early neurophysiological changes following prenatal immune challenge that may inform therapeutic interventions targeting hippocampal function.”
“Maternal infection during pregnancy is associated with an increased risk of neurodevelopmental disorders, including depression, schizophrenia, and autism spectrum disorder,” the authors wrote. Infection during pregnancy triggers an immune response that releases cytokines—chemical messengers that can cross the placenta and impact fetal brain development. “An acute infectious illness increases blood concentrations of inflammatory and anti-inflammatory cytokines and stress hormones, such as corticosteroids,” they continued. “These factors can pass the placenta, as well as the blood–brain barrier, and affect embryonal neurodevelopment.”
The hippocampus plays a critical role in these disorders, the team further noted, but the impact of maternal immune activation (MIA) on early hippocampal neuronal function isn’t well understood. For their newly reported study the investigators set out to test the hypothesis that, in rats, MIA leads to impaired functioning of hippocampal pyramidal neurons isolated from newborn offspring.
Using a well-established animal model, Dremencov and colleagues induced MIA in pregnant rats using lipopolysaccharide (LPS), a bacterial component that stimulates the immune system. They then examined the hippocampal neurons of newborn offspring to assess how such prenatal immune activation affected neuronal excitability. “Primary neuronal cultures were prepared from the hippocampi of newborn rats and maintained for 13 days in vitro (DIV13),” the team explained. “Whole-cell patch-clamp recordings assessed neuronal excitability parameters between DIV4-13.”
The study’s electrophysiological analyses revealed several major changes in hippocampal neuron function in newborns exposed to MIA. These included increased threshold potential, meaning that neurons required a stronger stimulus to activate, suggesting impaired excitability. The newborn hippocampal neurons also exhibited delayed action potential latency, taking longer to respond to stimulation, which affects signal transmission. In addition, they exhibited reduced peak potential and firing rates indicating lower neurotransmitter release.
Interestingly, there were sex-specific effects of MIA. Male offspring showed a greater reduction in spontaneous neuronal activity, which may have implications for the higher prevalence of certain neurodevelopmental disorders in males, the researchers suggested.
“We observed that neurons from MIA-exposed offspring had a significantly higher threshold for activation, slower response times, and reduced firing rates,” noted lead author Lucia Moravcikova, PhD. “This suggests a disruption in glutamatergic neurotransmission, which plays a critical role in learning, memory, and emotional regulation … One of the most striking aspects of our findings is the sex-specific vulnerability to prenatal inflammation. This could help explain why conditions like autism and schizophrenia are more commonly diagnosed in males.”
The authors further noted, “These alterations suggest impaired glutamatergic neurotransmission in the hippocampus of MIA offspring, with potential sex-specific effects observed for spontaneous activity … This reduced glutamatergic neurotransmission may contribute to the pathophysiology of neurodevelopmental disorders associated with maternal infection during pregnancy.”
The hippocampus is a crucial brain region involved in memory, emotion, and cognition, and its dysfunction has been implicated in multiple neurodevelopmental disorders. The study’s results support the hypothesis that prenatal immune challenges can disrupt early brain wiring, leading to long-term cognitive and behavioral impairments.
“Our findings align with human epidemiological studies linking maternal infection to an increased risk of psychiatric disorders,” said Dremencov. “Understanding how prenatal inflammation alters brain function could open the door to new preventative or therapeutic approaches.”
With growing evidence that prenatal inflammation affects brain function, researchers are now exploring strategies to mitigate these effects. Potential interventions might include the use of anti-inflammatory treatments during pregnancy to reduce excessive immune responses, or neuroprotective therapies that target disrupted neurotransmitter pathways to restore normal brain function.
“It is known that children of women suffering from an infectious disease during pregnancy have a higher risk of future development of depression, schizophrenia, and autism,” the authors concluded. “The results of the present study suggest that the early postnatal suppression of the excitability of hippocampal neurons might underline these epidemiological observations.”
Early-life interventions using techniques such as transcranial magnetic stimulation (TMS) may enhance neuronal excitability and connectivity. “If we can identify ways to prevent or reverse these changes in early development, we may be able to reduce the long-term burden of neurodevelopmental disorders,” said Dremencov. The authors further pointed out, “However, the risks and benefits of these interventions must be very carefully assessed … Animal models can be used in these assessments; however, the limitation of these models, which results from the difference between rodents and human brains, must be considered.”
Questions do remain, the authors acknowledged, including how the newly reported findings may translate to human brain development, and whether there is a specific time window during pregnancy when interventions might be most effective.