Inhibition of microRNA-203 protects against traumatic brain injury induced neural damages via suppressing neuronal apoptosis and dementia-related molecues

Background: Traumatic brain injury (TBI) can lead to cognitive dysfunction and motor dysfunction. TBI is a potential risk factor for subsequent dementia. Hyperphosphorylation of Tau and ApoE4 has been found in patients with TBI. A significant increase in miR-203 was also found in the peripheral blood of TBI mice. Thus, we hypothesize that miR-203 inhibitor protects against neuronal damage and behavioral deficits by inhibition of Tau phosphorylation, ApoE4 expression and apoptosis.

Methods: TBI mice were induced and treated with miR-203 inhibitor. Tau phosphorylation and ApoE4, hippocampal long-term potentiation (LTP), learning and memory, and motor function were separately detected by Western blot analysis, electrophysiology recording and behavioral assessments including Morris water maze test, beam-balance test, beam-walk test and rotarod test. Caspase-3 activity and bcl-2 expression were detected by ELISA.

Results: TBI induction led to increased phosphorylation of Tau and ApoE4 expression. Administration of miR-203 inhibitor suppressed TBI induced ApoE4 expression and Tau hyperphosphorylation, rescued TBI mediated hippocampal LTP deficits and hippocampus dependent learning and memory dysfunction. miR-203 inhibitor treatment also improved motor function. In addition, miR-203 inhibitor treatment inhibited neuronal apoptosis by inhibiting caspase-3 activity and increasing bcl-2 expression.

Conclusion: miR-203 inhibitor treatment can rescue TBI-induced neural damage by inhibiting neuronal apoptosis and dementia markers like ApoE4 expression and Tau phosphorylation.