Horgusluoglu Emrin, Nudelman Kelly, Nho Kwangsik, Saykin Andrew J
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, Indiana.
Am J Med Genet B Neuropsychiatr Genet. 2017 Jan;174(1):93-112. doi: 10.1002/ajmg.b.32429. Epub 2016 Feb 16.
New neurons are generated throughout adulthood in two regions of the brain, the olfactory bulb and dentate gyrus of the hippocampus, and are incorporated into the hippocampal network circuitry; disruption of this process has been postulated to contribute to neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. Known modulators of adult neurogenesis include signal transduction pathways, the vascular and immune systems, metabolic factors, and epigenetic regulation. Multiple intrinsic and extrinsic factors such as neurotrophic factors, transcription factors, and cell cycle regulators control neural stem cell proliferation, maintenance in the adult neurogenic niche, and differentiation into mature neurons; these factors act in networks of signaling molecules that influence each other during construction and maintenance of neural circuits, and in turn contribute to learning and memory. The immune system and vascular system are necessary for neuronal formation and neural stem cell fate determination. Inflammatory cytokines regulate adult neurogenesis in response to immune system activation, whereas the vasculature regulates the neural stem cell niche. Vasculature, immune/support cell populations (microglia/astrocytes), adhesion molecules, growth factors, and the extracellular matrix also provide a homing environment for neural stem cells. Epigenetic changes during hippocampal neurogenesis also impact memory and learning. Some genetic variations in neurogenesis related genes may play important roles in the alteration of neural stem cells differentiation into new born neurons during adult neurogenesis, with important therapeutic implications. In this review, we discuss mechanisms of and interactions between these modulators of adult neurogenesis, as well as implications for neurodegenerative disease and current therapeutic research. © 2016 Wiley Periodicals, Inc.
在成年期，新的神经元在大脑的两个区域产生，即嗅球和海马体的齿状回，并被整合到海马体网络电路中；据推测，这一过程的中断会导致包括阿尔茨海默病和帕金森病在内的神经退行性疾病。已知的成体神经发生调节因子包括信号转导通路、血管和免疫系统、代谢因子以及表观遗传调控。多种内在和外在因素，如神经营养因子、转录因子和细胞周期调节因子，控制神经干细胞的增殖、在成体神经发生微环境中的维持以及向成熟神经元的分化；这些因素在信号分子网络中起作用，这些信号分子在神经回路的构建和维持过程中相互影响，进而有助于学习和记忆。免疫系统和血管系统对于神经元的形成和神经干细胞命运的决定是必需的。炎症细胞因子响应免疫系统激活调节成体神经发生，而脉管系统调节神经干细胞微环境。脉管系统、免疫/支持细胞群体（小胶质细胞/星形胶质细胞）、黏附分子、生长因子和细胞外基质也为神经干细胞提供了一个归巢环境。海马体神经发生过程中的表观遗传变化也会影响记忆和学习。神经发生相关基因的一些遗传变异可能在成体神经发生过程中神经干细胞向新生神经元分化的改变中起重要作用，具有重要的治疗意义。在这篇综述中，我们讨论了这些成体神经发生调节因子的机制和相互作用，以及对神经退行性疾病的影响和当前的治疗研究。© 2016威利期刊公司
