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[神经发生的调控:影响成年哺乳动物大脑中新神经元形成的因素]

[Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain].

作者信息

Respondek Michalina, Buszman Ewa

机构信息

Wydział Farmaceutyczny z Oddziałem Medycyny Laboratoryjnej w Sosnowcu, Śląski Uniwersytet Medyczny w Katowicach, Katedra i Zakład Chemii i Analizy Leków w Sosnowcu.

出版信息

Postepy Hig Med Dosw (Online). 2015 Dec 31;69:1451-61.

Abstract

Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC), which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

摘要

神经发生是一个复杂的多步骤过程,可产生完全功能化的神经元。成人大脑中的这一过程基于多能神经元干细胞(NSC),这些干细胞能够增殖并分化为成熟的神经元或神经胶质细胞。NSC位于海马体内的颗粒下区和脑室下区。新神经元的形成取决于许多内源性和外源性因素,这些因素调节神经发生的每个步骤。本文描述了成体神经发生的最重要调节因子,主要包括:神经营养因子、生长因子、激素、神经递质和NSC的微环境。一些药物,尤其是抗精神病药、抗抑郁药和心境稳定剂可能会影响成人大脑的神经发生特性。此外,神经炎症、中风或癫痫等病理过程能够诱导NSC增殖。精神药物和病理过程的促神经发生作用与其增加某些激素和神经营养因子水平的能力有关,也与抗凋亡Bcl-2蛋白和金属蛋白酶MMP-2表达的升高有关。此外,一些药物,例如氟哌啶醇,能够阻断催乳素和多巴胺能神经母细胞受体。成体神经发生的下调与酒精滥用和高压力水平有关。许多药物,如细胞抑制剂、COX-2抑制剂和阿片类药物的负面影响也已被观察到。所述因素的促神经发生作用表明它们具有广泛的治疗潜力,并为许多神经精神疾病的有效和现代治疗提供了新的视角。这种作用还有助于阐明与成体脑细胞增殖和退化相关疾病的发病机制。

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