Evaluation of the role of FRMP on BDNF expression and signaling

Principal Investigator: 
University: 
University of Victoria
Faculty: 
Island Medical Program
Award Type: 

Fragile-X syndrome (FXS) is the most common form of inherited intellectual disability and is the best characterized form of autism spectrum disorder. This genetic condition is caused by a mutation in the FMR1 gene, leading to the functional loss of FMR1 protein (FMRP). Besides being important for neuronal development, this protein also exerts a strong influence on synaptic plasticity. As a matter of fact, FMRP is highly expressed in the dentate gyrus (DG) of the hippocampus, one of the few regions of the adult brain where the birth of new neurons takes place. 

To understand this relationship, it is important to clarify the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of FXS. BDNF is an important regulator of neural circuit development and function, and is thus strongly implicated in the development and treatment of several neurological conditions. Interestingly, it has been shown that BDNF and FMRP may reciprocally regulate each other.

However, BDNF is a complex signaling molecule, and its pro- and mature forms can elicit opposing biological effects. Thus, to fully understand the interaction between FMRP and BDNF it is important to study both its pro- and mature forms. Dr. Bettio will investigate how FMRP regulates BDNF/pro-BDNF expression in distinct brain regions and how changes in BDNF expression contribute to hippocampal circuit dysfunction and plasticity defects in FXS. 

The results of this study will expand scientific knowledge about the molecular mechanisms implicated in FXS, and will be key in the development of future BDNF-based therapeutic strategies.

 

Research Pillar: 
Host Institution: 
University of Victoria
Research Location: 
University of Victoria
Supervisor: 
Brian Christie
Year: 
2017