Elder Gregory A, De Gasperi Rita, Gama Sosa Miguel A
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.
Mt Sinai J Med. 2006 Nov;73(7):931-40.
Until recently neurogenesis in mammals was considered to occur only during the embryonic and early post-natal periods and to have no significant role in the adult nervous system. However, it is now accepted that neurogenesis occurs in two brain regions in adult mammals, namely, the hippocampus and olfactory bulb. In both regions new neurons arise from a resident population of neural progenitor cells that are maintained throughout adult life. Hippocampal neurogenesis is required for some types of hippocampal-dependent learning. Many factors enhance hippocampal neurogenesis including hormones, growth factors, drugs, neurotransmitters, and physical exercise as well as learning a hippocampal-dependent task. Other factors suppress hippocampal neurogenesis; these include aging, stress, glucocorticoids and stimuli that activate the pituitary/adrenal axis. Recently much attention has become focused on the relevance of hippocampal neurogenesis to the pathophysiology and treatment of mood disorders. Indeed all major pharmacological and non-pharmacological treatments for depression enhance hippocampal neurogenesis and suppressing hippocampal neurogenesis in mice blocks behavioral responses in some antidepressant-sensitive tests. Altered hippocampal neurogenesis may also play a pathophysiological role in neurodegenerative disorders such as Alzheimer's disease. How much neurogenesis occurs normally in other brain regions is unclear. Neural progenitors are found throughout the neuraxis including both neurogenic and non-neurogenic regions. When cultured in vitro or isolated and transplanted back into neurogenic brain regions, these cells can differentiate into neurons although in their in situ location they seem to behave as lineage-restricted glial progenitors. The environmental cues that limit the potential of progenitor cells in non-neurogenic brain regions are unknown. However, an emerging view is that astrocytes, a subset of which also functions as neural progenitor cells, are critical in regulating the local environment. After transplantation into adult brain, neural stem cells are capable of surviving and differentiating into both neurons and glial cells, offering hope that stem cell therapy may be utilized to treat a variety of neurological and perhaps psychiatric disorders. The widespread existence of endogenous neural progenitors even in non-neurogenic brain regions also offers hope that the potential of these cells may be harnessed to repair cellular injuries caused by injuries such as stroke, trauma or neurodegenerative diseases. While obstacles remain to both approaches, stem-cell-based therapies remain an area of intense research interest.
直到最近,哺乳动物的神经发生还被认为仅发生在胚胎期和出生后早期,在成年神经系统中没有显著作用。然而,现在人们已经接受,成年哺乳动物的两个脑区会发生神经发生,即海马体和嗅球。在这两个区域,新的神经元都源自一群终生存在的神经祖细胞。某些类型的海马体依赖性学习需要海马体神经发生。许多因素可促进海马体神经发生,包括激素、生长因子、药物、神经递质、体育锻炼以及学习海马体依赖性任务。其他因素则会抑制海马体神经发生,这些因素包括衰老、压力、糖皮质激素以及激活垂体/肾上腺轴的刺激。最近,海马体神经发生与情绪障碍的病理生理学及治疗的相关性受到了广泛关注。事实上,所有主要的抑郁症药物治疗和非药物治疗都会增强海马体神经发生,而抑制小鼠的海马体神经发生会阻断某些抗抑郁药敏感性测试中的行为反应。海马体神经发生的改变在诸如阿尔茨海默病等神经退行性疾病中可能也起病理生理作用。其他脑区正常情况下发生多少神经发生尚不清楚。神经祖细胞遍布整个神经轴,包括神经发生区和非神经发生区。当在体外培养或分离并移植回神经发生脑区时,这些细胞可以分化为神经元,尽管在其原位位置它们似乎表现为谱系受限的神经胶质祖细胞。限制非神经发生脑区祖细胞潜能的环境线索尚不清楚。然而,一种新出现的观点认为,星形胶质细胞(其中一部分也作为神经祖细胞发挥作用)在调节局部环境方面至关重要。移植到成年大脑后,神经干细胞能够存活并分化为神经元和神经胶质细胞,这为利用干细胞疗法治疗各种神经疾病甚至精神疾病带来了希望。内源性神经祖细胞即使在非神经发生脑区也广泛存在,这也带来了希望,即可以利用这些细胞的潜能来修复由中风、创伤或神经退行性疾病等损伤造成的细胞损伤。虽然这两种方法都仍存在障碍,但基于干细胞的疗法仍是一个备受关注的研究领域。