Features of the In Vitro Expression Profile of Hippocampal Neurogenic Niche Cells during Optogenetic Stimulation

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Pub Date : 2021-08-16 DOI:10.1134/S1990750821030057

E. D. Khilazheva, A. V. Morgun, E. B. Boytsova, A. I. Mosiagina, A. N. Shuvaev, N. A. Malinovskaya, Yu. A. Uspenskaya, E. A. Pozhilenkova, A. B. Salmina

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引用次数: 3

Abstract—

In the central nervous system of mammals, there are specialized areas, known as neurogenic niches, in which neurogenesis is observed in the postnatal period. It is believed that astrocytes in the composition of neurogenic niches play a significant role in the regulation of neurogenesis, and therefore they are considered as a promising “target” for the possible control of neurogenesis, including the use of optogenetics. In the framework of this study, we have formed an in vitro model of a neurogenic niche, consisting of cerebral endothelial cells, astrocytes, and neurospheres. Astrocytes in the neurogenic niche model expressed channelrhodopsin ChR2 and underwent photoactivation. The effect of photoactivated astrocytes on the expression profile of neurogenic niche cells was evaluated using methods of immunocytochemical analysis. It was found that intact astrocytes in the composition of the neurogenic niche promoted neuronal differentiation of stem cells, as well as the activation of astroglia expressing photosensitive proteins, changed expression of molecules characterized by intercellular interactions of pools of resting and proliferating cells in the composition of the neurogenic niche with the participation of NAD⁺ (Cx43, CD38, CD157), lactate (MCT1). The registered changes reflect: (i) impaired paracrine interactions between two subpopulations of cells, one of which acts as a source of NAD⁺, and another one is a consumer of NAD⁺ required for processes of the intracellular signal transduction; (ii) changes in the mechanisms of lactate transport due to aberrant expression of the lactate transporter MCT1 in cells forming a pool of cells developing along the neuronal path of differentiation (but not neuronal stem cells). In general, during photostimulation of niche astrocytes, the total proliferative activity increases mainly due to neural progenitor cells, but not neural stem cells. Thus, optogenetic activation of astrocytes can become a promising tool for controlling the activity of neurogenesis processes and the formation of a local proneurogenic microenvironment in an in vitro model of the neurogenic niche.

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光遗传刺激下海马神经源性小生境细胞体外表达谱的特征

在哺乳动物的中枢神经系统中，有一些专门的区域，被称为神经源性生态位，在那里可以观察到出生后的神经发生。人们认为星形胶质细胞在神经发生的调控中起着重要的作用，因此它们被认为是可能控制神经发生的一个有希望的“靶点”，包括光遗传学的使用。在这项研究的框架内，我们已经形成了一个体外神经源性生态位模型，由脑内皮细胞、星形胶质细胞和神经球组成。神经源性生态位模型中的星形胶质细胞表达通道视紫红质ChR2并进行光激活。采用免疫细胞化学方法评价光活化星形胶质细胞对神经源性小生境细胞表达谱的影响。研究发现，完整的星形胶质细胞在神经源性生态位的组成中促进了干细胞的神经元分化，并激活了表达光敏蛋白的星形胶质细胞，改变了NAD+ (Cx43, CD38, CD157)、乳酸盐(MCT1)参与的神经源性生态位组成中静止和增殖细胞池细胞间相互作用的分子表达。记录的变化反映了:(i)两个细胞亚群之间的旁分泌相互作用受损，其中一个作为NAD+的来源，另一个是细胞内信号转导过程所需的NAD+的消耗者;(ii)乳酸转运蛋白MCT1在沿神经元分化途径形成的细胞池(但不包括神经干细胞)中异常表达，从而改变了乳酸转运机制。一般来说，光刺激小生境星形胶质细胞时，总增殖活性的增加主要是由于神经祖细胞，而不是神经干细胞。因此，星形胶质细胞的光遗传学激活可以成为控制神经发生过程活性和局部前神经源性微环境形成的一个有前途的工具，在体外神经源性生态位模型中。

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来源期刊

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

1.10

自引率

0.00%

发文量

期刊介绍： Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.