O'Leary J D, O'Leary O F, Cryan J F, Nolan Y M
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
APC Microbiome Institute, University College Cork, Cork, Ireland.
Genes Brain Behav. 2018 Mar;17(3):e12357. doi: 10.1111/gbb.12357. Epub 2016 Nov 29.
The orphan nuclear receptor Tlx (Nr2e1) is a key regulator of both embryonic and adult hippocampal neurogenesis. Several different mouse models have been developed which target Tlx in vivo including spontaneous deletion models (from birth) and targeted and conditional knockouts. Although some conflicting findings have been reported, for the most part studies have demonstrated that Tlx is important in regulating processes that underlie neurogenesis, spatial learning, anxiety-like behaviour and interestingly, aggression. More recent data have demonstrated that disrupting Tlx during early life induces hyperactivity and that Tlx plays a role in emotional regulation. Moreover, there are sex- and age-related differences in some behaviours in Tlx knockout mice during adolescence and adulthood. Here, we discuss the role of Tlx in motor-, cognitive-, aggressive- and anxiety-related behaviours during adolescence and adulthood. We examine current evidence which provides insight into Tlx during neurodevelopment, and offer our thoughts on the function of Tlx in brain and behaviour. We further hypothesize that Tlx is a key target in understanding the emergence of neurobiological disorders during adolescence and early adulthood.
孤儿核受体Tlx（Nr2e1）是胚胎期和成年期海马神经发生的关键调节因子。已经开发了几种不同的小鼠模型，它们在体内靶向Tlx，包括自发缺失模型（从出生开始）以及靶向和条件性敲除模型。尽管已经报道了一些相互矛盾的发现，但大多数研究表明，Tlx在调节神经发生、空间学习、焦虑样行为以及有趣的攻击行为等潜在过程中很重要。最近的数据表明，在生命早期破坏Tlx会导致多动，并且Tlx在情绪调节中发挥作用。此外，在青春期和成年期，Tlx基因敲除小鼠的某些行为存在性别和年龄相关差异。在此，我们讨论Tlx在青春期和成年期运动、认知、攻击和焦虑相关行为中的作用。我们研究了当前能深入了解Tlx在神经发育过程中的证据，并对Tlx在大脑和行为中的功能提出了我们的看法。我们进一步推测，Tlx是理解青春期和成年早期神经生物学障碍出现情况的关键靶点。
