Inhibition of miR-206 Ameliorates Seizures and Cognitive Deficits via BDNF/TrkB Signaling in Pilocarpine-Induced TLE Mice

Objectives: Temporal lobe epilepsy (TLE) causes spontaneous seizures, hippocampal neuronal loss, and cognitive impairment. This study investigated whether miR-206 inhibition attenuates seizures and cognitive dysfunction by activating the BDNF/TrkB cascade in mice with pilocarpine-induced TLE. Methods: Fifty TLE-model C57BL/6N mice were divided into five groups. MiR-206 antagomir or a negative control was stereotaxically injected into the hippocampus. ANA-12, a TrkB inhibitor, was given intraperitoneally. We detected miR-206 with RT-qPCR. EEG was used to assess seizure activity. Spatial cognition was measured via the Morris water maze. Neuronal injury was evaluated using HE and Nissl staining. Target protein levels were quantified by Western blotting. Hippocampal miR-206 was elevated in TLE mice. Results: MiR-206 antagomir lowered miR-206 expression. It prolonged seizure latency. It reduced seizure frequency and duration. It restored spatial learning and memory function. It relieved CA3 neuronal loss and up-regulated BDNF/TrkB, SYP, and PSD95. ANA-12 abolished these protective phenotypes. Conclusions: MiR-206 inhibition confers anti-seizure, neuroprotective, and cognition-improving effects. These benefits depend on functional BDNF/TrkB signalling. miR-206 is a potential therapeutic target for TLE.