19th Annual Child Health Research Days

RBC Convention Center

Oct. 24 & 26, 2023


#54 Molecular Deregulation of Brain Derived Neurotrophic Factor in the Brain of Rett Syndrome Patients.

Shervin Pejhan, University of Manitoba; Marc Del Bigio, University of Manitoba; Victoria Siu, Western University; Lee Cyn Ang, Western University; Mojgan Rastegar, University of Manitoba


MECP2 (methyl CpG binding protein 2) gene mutations cause Rett Syndrome (RTT), a severe neurological disorder in young children, affecting mainly females who seem to be normal at birth, but by 6-18 months of age, they develop delay and regression in their developmental milestones affecting speech, hand skills, and gait, accompanied by stereotypical hand movements, seizures, and autonomic abnormalities Alterations in the Brain Derived Neurotrophic Factor (BDNF) signaling has been suggested as a contributing factor in the pathophysiology of Rett syndrome. However, the research in this area is mainly based on experiments using male, Mecp2-null animals which is far from the real condition of almost exclusively female RTT patients with different types of mutations in MECP2 gene.


In the present project, we investigate the BDNF dysregulation in female human brain cells after achieving MECP2 knock down by CRISPR editing method. Furthermore, for adding relevance to the implication of BDNF dysregulation as part of the etiology of Rett syndrome, we examine four regions of human brain tissue with different RTT- causing mutations versus their normal controls for the transcript level of BDNF as well as its protein in both precursor and mature forms. We also study the correlation between the level of MeCP2 isoforms and BDNF in normal versus pathologic conditions, and we show how the type of MECP2 mutation may affect this correlation.


Brain samples of our Rett syndrome patients showed lower level of transcript for MeCP2 isoforms and BDNF, but the change at protein level was not similar. A brain region and mutation-specific trend is suggested.


The outcome of this research is expected to illuminate the path to the modulation of BDNF in neurodevelopmental disorders for therapeutic purposes.