Pinosanu Leonard Radu, Capitanescu Bogdan, Glavan Daniela, Godeanu Sanziana, Cadenas Israel Ferna Ndez, Doeppner Thorsten R, Hermann Dirk M, Balseanu Adrian-Tudor, Bogdan Catalin, Popa-Wagner Aurel
1Experimental Research Center for Normal and Pathological Aging (ARES), University of Medicine and Pharmacy of Craiova, Craiova, Romania.
2Psychiatric clinic, University of Medicine and Pharmacy Craiova, Craiova, Romania.
Aging Dis. 2023 Feb 1;14(1):63-83. doi: 10.14336/AD.2022.0621.
Glia cells are essential for brain functioning during development, aging and disease. However, the role of astroglia plays during brain development is quite different from the role played in the adult lesioned brain. Therefore, a deeper understanding of pathomechanisms underlying astroglia activity in the aging brain and cerebrovascular diseases is essential to guide the development of new therapeutic strategies. To this end, this review provides a comparison between the transcriptomic activity of astroglia cells during development, aging and neurodegenerative diseases, including cerebral ischemia. During fetal brain development, astrocytes and microglia often affect the same developmental processes such as neuro-/gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis, and synaptic pruning. In the adult brain astrocytes are a critical player in the synapse remodeling by mediating synapse elimination while microglia activity has been associated with changes in synaptic plasticity and remove cell debris by constantly sensing the environment. However, in the lesioned brain astrocytes proliferate and play essential functions with regard to energy supply to the neurons, neurotransmission and buildup of a protective scar isolating the lesion site from the surroundings. Inflammation, neurodegeneration, or loss of brain homeostasis induce changes in microglia gene expression, morphology, and function, generally referred to as "primed" microglia. These changes in gene expression are characterized by an enrichment of phagosome, lysosome, and antigen presentation signaling pathways and is associated with an up-regulation of genes encoding cell surface receptors. In addition, primed microglia are characterized by upregulation of a network of genes in response to interferon gamma. . A comparison of astroglia cells transcriptomic activity during brain development, aging and neurodegenerative disorders might provide us with new therapeutic strategies with which to protect the aging brain and improve clinical outcome.
神经胶质细胞在大脑发育、衰老和疾病过程中对大脑功能至关重要。然而，星形胶质细胞在大脑发育过程中所起的作用与在成人大脑损伤中所起的作用截然不同。因此，深入了解衰老大脑和脑血管疾病中星形胶质细胞活动的病理机制对于指导新治疗策略的开发至关重要。为此，本综述比较了星形胶质细胞在发育、衰老和神经退行性疾病（包括脑缺血）过程中的转录组活性。在胎儿大脑发育过程中，星形胶质细胞和小胶质细胞常常影响相同的发育过程，如神经/胶质细胞生成、血管生成、轴突生长、突触形成和突触修剪。在成人大脑中，星形胶质细胞通过介导突触消除在突触重塑中起关键作用，而小胶质细胞的活动与突触可塑性的变化相关，并通过不断感知环境来清除细胞碎片。然而，在受损大脑中，星形胶质细胞会增殖，并在为神经元提供能量、神经传递以及形成将损伤部位与周围环境隔离开的保护性瘢痕方面发挥重要作用。炎症、神经退行性变或脑稳态的丧失会诱导小胶质细胞基因表达、形态和功能的变化，通常称为“预激”小胶质细胞。这些基因表达的变化以吞噬体、溶酶体和抗原呈递信号通路的富集为特征，并与编码细胞表面受体的基因上调相关。此外，预激小胶质细胞的特征是响应干扰素γ而上调一组基因网络。比较星形胶质细胞在大脑发育、衰老和神经退行性疾病过程中的转录组活性可能会为我们提供新的治疗策略，以保护衰老大脑并改善临床结果。
