How a common variant in the growth factor receptor gene, NTRK1, affects white matter

Abstract

Growth factors and their receptors are important for cellular migration as well as axonal guidance and myelination in the brain. They also play a key role in programmed cell death, and are implicated in a number of mental illnesses. Recently, we reported that healthy young adults who carry the T allele variant in the growth factor gene, NTRK1 (at location rs6336), had lower white matter integrity than non-carriers on diffusion images of the brain. Diffusion tensor imaging (DTI) revealed how this single nucleotide polymorphism affects white matter microstructure in human populations; DTI is also used to identify characteristic features of brain connectivity in typically developing children and in patients. Newly discovered links between neuroimaging measures and growth factors whose molecular neuroscience is well known offer an important step in understanding mechanisms that contribute to brain connectivity. Altered fiber connectivity may mediate the relationship between some genetic risk factors and a variety of mental illnesses.

Keywords: :

• neurotrophin
• growth factor
• tropomyosin-related kinase receptor A
• neurotrophic tyrosine kinase receptor 1
• myelin
• development
• fractional anisotropy
• radial diffusivity
• diffusion tensor imaging
• schizophrenia

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank the twins and siblings for their participation. In Brisbane, we thank Marlene Grace and Ann Eldridge for twin recruitment, Aiman Al Najjar and other radiographers for scanning, Kerrie McAloney and Daniel Park for research support, and staff in the Molecular Epidemiology Laboratory for DNA sample processing and preparation. This study was supported by the National Institute of Child Health and Human Development (R01 HD050735), and the National Health and Medical Research Council (NHMRC 486682), Australia. Genotyping was supported by the NHMRC (grant 389875). Additional support was provided by NIH R01 grants AG040060, EB008432, EB008281, and EB007813. MNB was funded in part by the NIH (P50 AG-16570) and by the UCLA Easton Consortium for Biomarker and Drug Discovery in Alzheimer Disease. G.Z. is supported by an ARC Future Fellowship (FT0991634). We thank Emily Dennis for preparing the figure included here.