Role of the gestational maternal gut-microbiota in the neurodevelopment of the hypothalamus and the amygdala

The maternal gestational gut-microbiota has emerged as a potent modulator of neurodevelopment and increasing evidence links its alteration in the etiology of neurodevelopmental and neuropsychiatric conditions. The alar hypothalamus and the medial extended amygdala (EAme) are two key nodes of the social brain closely associated to these disorders. Notably, perinatal microbiota changes have been linked with morphological alterations in both brain regions. Moreover, microbiota-based interventions can modulate endogenous oxytocin levels in the hypothalamus. Hence, we hypothesized that the maternal microbiota influences the development of the alar hypothalamus and the EAme. To address this hypothesis, we used antibiotic treatment to deplete the maternal gestational gut microbiota in pregnant mouse females. Subsequently, we collected embryonic brains at E15.5 and examined radial glia (RG) led neurodevelopmental processes via immunofluorescence in two embryonic domains controlling the specification of both the EAme and alar hypothalamus: the telencephalon-opto-hypothalamic domain (TOH) and the supraopto-paraventricular hypothalamic domain core part (SPVco), respectively. Our findings reveal a decreased number of RG endfeet in the ventricular zone in the SPVco but not in the TOH in antibiotic treated mice compare to controls. In addition, both domains exhibited increased number of mantle zone radial glia in antibiotic treated mice. Collectively, these data suggest that maternal gestational microbiota modulates the production and dynamics of radial glia progenitors, potentially leading to morphological defects in both areas. Further research is warranted to elucidate its role in the differentiation and specification of the neuronal populations within these regions.