Maternal immune activation produces neonatal excitability defects in offspring hippocampal neurons from pregnant rats treated with poly I:C

Abstract

Maternal immune activation (MIA) resulting from prenatal exposure to infectious pathogens or inflammatory stimuli is increasingly recognized to play an important etiological role in neuropsychiatric disorders with neurodevelopmental features. MIA in pregnant rodents induced by injection of the synthetic double-stranded RNA, Poly I:C, a mimic of viral infection, leads to a wide spectrum of behavioral abnormalities as well as structural and functional defects in the brain. Previous MIA studies using poly I:C prenatal treatment suggested that neurophysiological alterations occur in the hippocampus. However, these investigations used only juvenile or adult animals. We postulated that MIA-induced alterations could occur earlier at neonatal/early postnatal stages. Here we examined the neurophysiological properties of cultured pyramidal-like hippocampal neurons prepared from neonatal (P0-P2) offspring of pregnant rats injected with poly I:C. Offspring neurons from poly I:C-treated mothers exhibited significantly lower intrinsic excitability and stronger spike frequency adaptation, compared to saline. A similar lower intrinsic excitability was observed in CA1 pyramidal neurons from hippocampal slices of two weeks-old poly I:C offspring. Cultured hippocampal neurons also displayed lower frequency of spontaneous firing, higher charge transfer of IPSCs and larger amplitude of miniature IPSCs. Thus, maternal immune activation leads to strikingly early neurophysiological abnormalities in hippocampal neurons.

Maternal immune activation alters glutamic acid decarboxylase-67 expression in the brains of adult rat offspring

“…It is also possible that the developmental alteration in hippocampal GAD 67 expression observed in our study reflects a relative imbalance of hippocampal excitatory/inhibitory function. Previous studies have consistently identified altered indices of hippocampal function in the MIA model (Lanté et al, 2007; Lowe et al, 2008; Bitanihirwe et al, 2010; Oh-Nishi et al, 2010; Escobar et al, 2011; Ducharme et al, 2012; Dickerson and Bilkey, 2013; Patrich et al, 2016a,b). …”

Descriptive epidemiology of prenatal and perinatal risk factors in a Chinese population with reading disorder

“…The mechanism for this probably involves the maternal immune response which may have an effect on the foetus. Maternal immune activation (MIA) resulting from prenatal exposure to infectious pathogens or inflammatory stimuli is increasingly recognised as playing an important etiological role in neuropsychiatric disorders with neurodevelopmental features31. The Interleukin-17a pathway, which is involved in the MIA of the virally infected mother, has been reported to induce behavioural abnormalities in offspring in rodent testing32.…”

Maternal immune activation: Implications for neuropsychiatric disorders

“…Several studies have also recently reported deficits in dendritic spine density, levels of synaptic proteins, synaptic transmission, long-term plasticity, and cortical malformations(4, 19–24). However, most of these measures have been studied in single brain regions from single models at a single age.…”