Naik Aijaz Ahmad, Patro Nisha, Seth Pankaj, Patro Ishan K
School of Studies in Neuroscience, Jiwaji University, Gwalior 474011, India.
School of Studies in Zoology, Jiwaji University, Gwalior 474011, India.
Biol Open. 2017 Jul 15;6(7):931-942. doi: 10.1242/bio.023432.
The lack of information on astrogenesis following stressor effect, notwithstanding the 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 AB+ glia restricted precursor population in ventricles and caused poor dissemination to cortex at embryonic days (E)11-14, and low BLBP+ secondary radial glia in the subventricular zone (SVZ) of E16 low protein (LP) brains reflect compromised progenitor pooling. Contrary to large-sized BLBP+ gliospheres in high protein (HP) brains 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 suggest 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 of astrocytes as possible drivers of neurodevelopmental disorders. This study may increase our understanding of stressor-associated brain development, opening up windows for effective therapeutic interventions against debilitating neurodevelopmental disorders.
尽管星形胶质细胞在正常生理和病理生理中起着至关重要的作用，但关于应激源作用后星形胶质细胞生成的信息却很匮乏，这促使我们在代内蛋白质营养不良（PMN）大鼠模型中评估星形胶质细胞生成的时间进程和星形胶质细胞密度。我们采用了针对神经胶质谱系标志物的标准免疫组织化学程序及其强度测量方法，以及定量逆转录聚合酶链反应（qRT-PCR）研究，以揭示星形胶质细胞的时空起源和密度。在胚胎期（E）11 - 14，AB + 神经胶质细胞前体数量减少，限制了脑室中的前体细胞群，并导致向皮质的扩散不佳，而E16低蛋白（LP）脑的脑室下区（SVZ）中低水平的BLBP + 二级放射状神经胶质细胞反映了祖细胞池的受损。与E16高蛋白（HP）脑中大尺寸的BLBP + 神经球相反，LP脑中的小神经球和离散的BLBP + 细胞表明其定植能力丧失和增殖潜力低下。GFAP表达的延迟出现、星形胶质细胞的早熟成熟以及星形胶质细胞数量的显著减少表明LP - F1脑内星形胶质细胞生成的时间受损且受到损害。我们关于蛋白质剥夺导致星形胶质细胞生成时间受损、密度降低和星形胶质细胞功能障碍的研究结果，强化了星形胶质细胞可能是神经发育障碍驱动因素的假说。这项研究可能会增进我们对应激源相关脑发育的理解，为针对使人衰弱的神经发育障碍的有效治疗干预打开窗口。
