Investigating the role of brain‐derived neurotrophic factor in relapsing–remitting multiple sclerosis

Abstract

Multiple sclerosis (MS) is a common, heterogeneous disorder of the central nervous system with a complex trait composed of both genetic and environmental factors. Recently, scientific interest has increased in defining factors that possibly contribute to brain functional plasticity; the results might be useful to assess the relationship between MS lesion burden and clinical events, as well as explaining the well-known phenotypic heterogeneity of the disease. In this study, we explored the effect of the Val66Met brain-derived neurotrophic factor (BDNF) functional polymorphism on cognitive performances and volumetric measurements obtained by magnetic resonance imaging of the brain in a selected population of relapsing-remitting MS (RRMS) patients, with relatively short disease duration and minimal clinical disability, compared to gender, age and educationallevel matched healthy subjects. We found that in the RRMS group, the BDNF Met-allele was significantly associated with the lower volume of cerebral grey matter (GM) (P = 0.005). Furthermore, a significant (P = 0.013) interaction effect between 'MS-status' and the BDNF genotype was found for GM volumes, with the result that patients carrying the BDNF Met-allele showed a higher risk of developing global GM atrophy than the homozygous Val/Val. No BDNF-related impact on global neuropsychological functions resulted in either RRMS patients or controls. Our data seem to be consistent with the reported influence of BDNF in neuronal plasticity, thus suggesting that the Met-allele might have a negative prognostic effect on cortical morphometry in RRMS patients.

Sexually dimorphic effect of the Val66Met polymorphism of BDNF on susceptibility to Alzheimer's disease: New data and meta‐analysis

“…It is reasonable to assume that the Met66 is associated with lower secretion of BDNF, which could result in attenuation of the survival signal of BDNF, compared with the Val66. In accordance with this, individuals carrying the Met66 allele have been reported to have decreased brain structures (e.g., hippocampus) than those individuals who did not carry the allele [Pezawas et al, 2004;Szeszko et al, 2005;Agartz et al, 2006;Bueller et al, 2006;Ho et al, 2006;Nemoto et al, 2006;Frodl et al, 2007;Liguori et al, 2007]. Of note, we found that female individuals carrying the Met66 allele showed more widespread ageassociated volume reduction in the dorsolateral prefrontal cortices than male Met66 carriers [Nemoto et al, 2006].…”

Effects of the BDNF Val66Met Polymorphism on White Matter Microstructure in Healthy Adults

“…Conflicting information is also present in regards to the effects of Val 66 Met on T2 hyperintensity lesion load in multiple sclerosis, an index of prominent dysmyelination. The only investigation to examine a relatively large population (n ¼ 209) found that the Met allele was associated with diminished lesion load as compared with Val/Val (Zivadinov et al, 2007) , but this result has not been confirmed in smaller cohorts (Dinacci et al, 2011;Liguori et al, 2007). Nevertheless, T2 hyperintensities are not found in our samples and cannot explain our results.…”

MAO A VNTR polymorphism and variation in human morphology: a VBM study

“…The MAO A promoter region polymorphism, the Val 158 Met COMT, and Val 66 Met BDNF polymorphisms were genotyped on the basis of previously described methods [5,16,17].…”