Intra-generational protein malnutrition impairs temporal astrogenesis in rat brain

Abstract

The scanty information on astrogenesis following stressor effect, albeit imperative roles of astroglia in normal physiology and pathophysiology, incited us to assess temporal astrogenesis and astrocyte density in an intra-generational protein malnutrition (PMN) rat model. Standard immunohistochemical procedures for glial lineage markers and their intensity measurements and qRT-PCR studies were performed to reveal the spatio-temporal origin and density of astrocytes. Reduced A2B5+ glia restricted precursor population in ventricles and poor dissemination to cortex at embryonic days (E)11-14, low BLBP+ secondary radial glia in SVZ of E16 LP brains reflect compromised progenitor pooling. Contrary to large sized BLBP+ gliospheres in HP at E16, small gliospheres and discrete BLBP+ cells in LP brains evidence loss of colonization and low proliferative potential. Delayed emergence of GFAP expression, precocious astrocyte maturation and significantly reduced astrocyte number speculate impaired temporal and compromised astrogenesis within LP-F1 brains. Our findings of protein deprivation induced impairments in temporal astrogenesis, compromised density and astrocytic dysfunction, strengthen the hypothesis “astrocytes as possible drivers of neurodevelopmental disorders” and may increase our understanding of stressor associated brain development, opening up windows for effective therapeutic interventions against debilitating neurodevelopmental disorders.