Department of Anatomy and Neuroscience, University College Cork, Ireland.
Department of Anatomy, National University of Ireland, Galway, Ireland.
J Neuroimmunol. 2019 Jun 15;331:87-96. doi: 10.1016/j.jneuroim.2017.08.008. Epub 2017 Aug 20.
The orphan nuclear receptor TLX (Nr2e1) is a key regulator of hippocampal neurogenesis. Impaired adult hippocampal neurogenesis has been reported in neurodegenerative and psychiatric conditions including dementia and stress-related depression. Neuroinflammation is also implicated in the neuropathology of these disorders, and has been shown to negatively affect hippocampal neurogenesis. To investigate a role for TLX in hippocampal neuroinflammation, we assessed microglial activation in the hippocampus of mice with a spontaneous deletion of TLX. Results from our study suggest that a lack of TLX is implicated in deregulation of microglial phenotype and that consequently, the survival and function of newborn cells in the hippocampus is impaired. TLX may be an important target in understanding inflammatory-associated impairments in neurogenesis.
孤儿核受体 TLX（Nr2e1）是海马神经发生的关键调节因子。在包括痴呆症和与应激相关的抑郁症在内的神经退行性和精神疾病中，已报道成年海马神经发生受损。神经炎症也与这些疾病的神经病理学有关，并已显示出对海马神经发生有负面影响。为了研究 TLX 在海马神经炎症中的作用，我们评估了自发缺失 TLX 的小鼠海马中的小胶质细胞激活。我们的研究结果表明，TLX 的缺乏与小胶质细胞表型的失调有关，因此，海马中新细胞的存活和功能受损。TLX 可能是理解与炎症相关的神经发生损伤的重要靶点。
