Medical School of Yangtze University, Yangtze, People's Republic of China.
Radiobiology Research Laboratory, Singapore Nuclear Research and Safety Initiative, National University of Singapore, Singapore, Singapore.
Curr Neurol Neurosci Rep. 2016 Feb;16(2):20. doi: 10.1007/s11910-015-0616-3.
The mobilization of endogenous neural stem cells in order to substitute lost neurons in the adult brain may reduce the negative effects of patients with chronic neurodegenerative diseases. However, abnormal neurogenesis may be harmful and could lead to the worsening of patients' symptoms. In the brains of patients and animal models with temporal lobe epilepsy (TLE), increased newly generated neurons in the subgranular zone (SGZ) at early stages after brain insults have been speculated to be involved in epileptogenesis. However, this argument is unsupported by evidence showing that (1) hippocampal neurogenesis is reduced at chronic stages of intractable TLE, (2) decreased neurogenesis is involved in epileptogenesis, and (3) spontaneous recurrent seizures occur before newly generated neurons are integrated into hippocampal neural pathways. Therefore, the hypothesis of increased neurogenesis in epileptogenesis may need to be re-evaluated. In this paper, we systemically reviewed brain neurogenesis and relevant molecules in the regulation of neurogenesis in SGZ. We aimed to update researchers and epileptologists on current progresses on pathophysiological changes of neurogenesis at different stages of TLE in patients and animal models of TLE. The interactions among neurogenesis, epileptogenesis and cognitive impairment, and molecules' mechanism involved in neurogenesis would also be discussed. Future research directions are proposed at the end of this paper.
为了替代成年大脑中丢失的神经元而动员内源性神经干细胞,可能会减轻慢性神经退行性疾病患者的负面影响。然而,异常的神经发生可能是有害的,并可能导致患者症状恶化。在颞叶癫痫(TLE)患者和动物模型的大脑中,人们推测在脑损伤后的早期阶段,颗粒下区(SGZ)中新生神经元的增加与癫痫发生有关。然而,这一论点没有证据支持,因为有证据表明:(1)在难治性 TLE 的慢性阶段,海马神经发生减少;(2)神经发生减少与癫痫发生有关;(3)自发性反复性癫痫发作发生在新生神经元整合到海马神经通路之前。因此,癫痫发生中神经发生增加的假说可能需要重新评估。在本文中,我们系统地回顾了 SGZ 中脑神经发生和相关分子对神经发生的调节。我们旨在让研究人员和癫痫学家了解 TLE 患者和 TLE 动物模型不同阶段神经发生的病理生理学变化的最新进展。我们还将讨论神经发生、癫痫发生和认知障碍之间的相互作用,以及神经发生中涉及的分子机制。本文最后提出了未来的研究方向。