PLoS One：TG2的识别或有助于开发新型抑郁症疗法

近日，一项刊登在国际杂志PLoS One上的研究报告指出，将两种分子（一种分子在抑郁症中水平降低，一种分子在使用抗抑郁症药物后水平升高）结合起来，或可以产生出治疗抑郁症的新药。血清素（Serotonin）是一种神经递质，其可以使大脑细胞之间互相交流以及产生脑源性神经生长因子（BDNF），BDNF是一种大脑营养因子可以补充神经细胞之间的连接性。流行的抗抑郁药比如百优解，可以增加血清素的水平，其也可以增加BDNF的水平，研究这样说。

研究者表示，我们并不知道在抑郁症研究中已经研究很清楚的血清素可以调节BDNF的信号路径。研究者预测了一种关键的蛋白谷氨酰胺转移酶2或称为TG2，其被大脑细胞和许多其它类型的细胞所表达。TG2在天然的血清素循环中扮演着重要角色，也是血清素缺失相关抑郁症的影响因子。而且其可以帮助解释为什么血清素和BDNF的水平可以同步升高或者降低。

TG2可以将血清素隐藏为蛋白质Rac1，该蛋白质可以使得BDNF受体恢复活力，并吸附至大脑细胞表面，但是可以周期性地移动到细胞表面复苏。抑郁症表现出了这些复合物之间的不平衡，研究者假设高水平的TG2促使血清素补给大脑脑细胞的交流，相反，会产生大量的Rac1，但是Rac1的降解也会随之增加，直到最终BDNF信号慢慢降低。

目前的一个问题是，是否当前的抗抑郁症药可以影响TG2，为了阐明损伤BDNF受体的角色，研究者想研究指导是否给予抑郁症模型BDNF可以使其更加抑郁？研究者使用病毒颗粒直接激活了BDNF受体，同样也给予了TG2抑制剂半胱胺，结果表明，抑制剂在使抑郁症行为正常化方面表现出了作用，以及使得BDNF的水平也回归到了正常。

某些抗抑郁药，如百忧解，其可以干扰天然的血清素循环以便血清素可用，以便来促进细胞之间的交流。研究者表示，他们后期会进行深入研究来进一步解析其具体的分子机理，而且研究者希望其研究可以早日开发出治疗抑郁症的新型疗法。

编译自：Studies Seek Better Understanding and Treatment of Depression

doi:10.1371/journal.pone.0039358
PMC:
PMID:

Plasma BDNF Levels Vary in Relation to Body Weight in Females

Anilkumar Pillai1*, Davide Bruno2,5, Antero S. Sarreal2, Raymundo T. Hernando2, Leslie A. Saint-Louis3, Jay Nierenberg4,5, Stephen D. Ginsberg4,5, Nunzio Pomara2,5, Pankaj D. Mehta6, Henrik Zetterberg7, Kaj Blennow7, Peter F. Buckley1

Brain derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression as well as neuropsychiatric and neurodegenerative disorders. Recent studies show a role of BDNF in energy metabolism and body weight regulation. We examined BDNF levels in plasma and cerebrospinal fluid (CSF) samples from age matched elderly depressed and control subjects. Also, the association of BDNF levels with age, gender, body weight, body mass index (BMI), and cognitive performance was evaluated. We did not find any significant differences in plasma and CSF BDNF levels between depressed and control subjects. Plasma BDNF levels were negatively correlated with age (but not with BMI and body weight), when analyses were performed including both depressed and control subjects. A significant reduction in plasma BDNF levels was observed in females as compared to male subjects, and the change in BDNF levels were significantly and positively related to body weight in females. Furthermore, significant increases in Total Recall and Delayed Recall values were found in females as compared to males. In conclusion, the lower BDNF levels observed in females suggest that changes in peripheral BDNF levels are likely secondary to an altered energy balance. However, further studies using larger sample size are warranted.