Suppression of FoxO3a attenuates neurobehavioral deficits after traumatic brain injury through inhibiting neuronal autophagy.

Suppression of FoxO3a attenuates neurobehavioral deficits after traumatic brain injury through inhibiting neuronal autophagy. Behav Brain Res. 2017 Sep 06;: Authors: Sun L, Zhao M, Liu M, Su P, Zhang J, Li Y, Yang X, Wu Z Abstract Traumatic brain injury (TBI) is a serious insult that frequently leads to neurological impairments. Forkhead box O (FoxO) 3a, as transcription factor, has been confirmed to modulate autophagic process. Moreover, FoxO3a is expressed throughout the brain including the hippocampus. However, the role of FoxO3a in the pathophysiology of TBI is unclear. The present study is designed to investigate whether FoxO3a has the neuroprotective effects on rats subjected to TBI, and further to explore the potential molecular mechanisms. Thus, a rat model of TBI was created by using a modified weight-drop device to mimic the insults of TBI. The results showed that FoxO3a was significantly increased in the serum of patients with TBI as well as in experimental animals. Furthermore, our data also demonstrated that TBI stimulated the translocation of FoxO3a from the cytosol to the nucleus. Additionally, we found that knockdown of FoxO3a by siRNA silencing significantly improved neurobehavioral dysfunctions and conferred a better neuroprotective effects after TBI, evidenced by promoting motor behavioral recovery, attenuating learning and memory impairments, and partially reversing neuronal damage in the hippocampus. To further i...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research