Repetitive Transcranial Magnetic Stimulation Alleviates Neurological Deficits After Cerebral Ischemia Through Interaction Between RACK1 and BDNF exon IV by the Phosphorylation-Dependent Factor MeCP2.

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is acknowledged as a form of neurostimulation, especially for functional recovery. The foundational knowledge of molecular mechanism is limited regarding its role in cerebral ischemia, for which the present study was designed. Primary neurons were treated with oxygen-glucose deprivation (OGD) and repetitive magnetic stimulation (rMS), in which brain-derived neurotrophic factor (BDNF) and transcription of BDNF exons were examined. Then, adenovirus vectors carrying siRACK1 sequence were delivered to primary neurons, followed by detection of the transcription of BDNF exons and the extent of methyl CpG binding protein 2 (MeCP2) phosphorylation. Results showed that BDNF and the transcription of BDNF exons were upregulated by rMS and OGD treatment, but decreased by extra treatment of RACK1 siRNA. Then, the mechanism investigations demonstrated that rMS increased the extent of MeCP2 phosphorylation to promote the interaction between RACK1 and BDNF exon IV. The aforementioned findings were further confirmed in vivo in middle cerebral artery occlusion (MCAO)-induced rat models, as indicated by improved neurological functions and reduced area of cerebral infarction. The study offers potential evidence for improvement of neurological deficits, highlighting the important role of rTMS for treatment of cerebral ischemia.