Dataset Information

The BDNF Val66Met Polymorphism (rs6265) Modulates Inflammation and Neurodegeneration in the Early Phases of Multiple Sclerosis.

ABSTRACT: The clinical course of multiple sclerosis (MS) is critically influenced by the interplay between inflammatory and neurodegenerative processes. The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265), one of the most studied single-nucleotide polymorphisms (SNPs), influences brain functioning and neurodegenerative processes in healthy individuals and in several neuropsychiatric diseases. However, the role of this polymorphism in MS is still controversial. In 218 relapsing-remitting (RR)-MS patients, we explored, at the time of diagnosis, the associations between the Val66Met polymorphism, clinical characteristics, and the cerebrospinal fluid (CSF) levels of a large set of pro-inflammatory and anti-inflammatory molecules. In addition, associations between Val66Met and structural MRI measures were assessed. We identified an association between the presence of Met and a combination of cytokines, identified by principal component analysis (PCA), including the pro-inflammatory molecules MCP-1, IL-8, TNF, Eotaxin, and MIP-1b. No significant associations emerged with clinical characteristics. Analysis of MRI measures evidenced reduced cortical thickness at the time of diagnosis in patients with Val66Met. We report for the first time an association between the Val66Met polymorphism and central inflammation in MS patients at the time of diagnosis. The role of this polymorphism in both inflammatory and neurodegenerative processes may explain its complex influence on the MS course.

SUBMITTER: Dolcetti E

PROVIDER: S-EPMC8871843 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The BDNF Val66Met Polymorphism (rs6265) Modulates Inflammation and Neurodegeneration in the Early Phases of Multiple Sclerosis.

Dolcetti Ettore E Bruno Antonio A Azzolini Federica F Gilio Luana L Moscatelli Alessandro A De Vito Francesca F Pavone Luigi L Iezzi Ennio E Gambardella Stefano S Giardina Emiliano E Ferese Rosangela R Buttari Fabio F Rizzo Francesca Romana FR Furlan Roberto R Finardi Annamaria A Musella Alessandra A Mandolesi Georgia G Guadalupi Livia L Centonze Diego D Stampanoni Bassi Mario M

Genes 20220210 2

The clinical course of multiple sclerosis (MS) is critically influenced by the interplay between inflammatory and neurodegenerative processes. The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265), one of the most studied single-nucleotide polymorphisms (SNPs), influences brain functioning and neurodegenerative processes in healthy individuals and in several neuropsychiatric diseases. However, the role of this polymorphism in MS is still controversial. In 218 relapsing-remi ...[more]

PMID: 35205376

Similar Datasets

Project description:Episodic memory deficits are frequent symptoms in Multiple Sclerosis and have been associated with dysfunctions of the hippocampus, a key region for learning. However, it is unclear whether genetic factors that influence neural plasticity modulate episodic memory in MS. We thus studied how the Brain Derived Neurotrophic Factor Val(66)Met genotype, a common polymorphism influencing the hippocampal function in healthy controls, impacted on brain networks underlying episodic memory in patients with Multiple Sclerosis. Functional magnetic resonance imaging was used to assess how the Brain Derived Neurotrophic Factor Val(66)Met polymorphism modulated brain regional activity and functional connectivity in 26 cognitively unimpaired Multiple Sclerosis patients and 25 age- and education-matched healthy controls while performing an episodic memory task that included encoding and retrieving visual scenes. We found a highly significant group by genotype interaction in the left posterior hippocampus, bilateral parahippocampus, and left posterior cingulate cortex. In particular, Multiple Sclerosis patients homozygous for the Val(66) allele, relative to Met(66) carriers, showed greater brain responses during both encoding and retrieval while the opposite was true for healthy controls. Furthermore, a robust group by genotype by task interaction was detected for the functional connectivity between the left posterior hippocampus and the ipsilateral posterior cingulate cortex. Here, greater hippocampus-posterior cingulate cortex connectivity was observed in Multiple Sclerosis Met(66) carriers relative to Val(66) homozygous during retrieval (but not encoding) while, again, the reverse was true for healthy controls. The Val(66)Met polymorphism has opposite effects on hippocampal circuitry underlying episodic memory in Multiple Sclerosis patients and healthy controls. Enhancing the knowledge of how genetic factors influence cognitive functions may improve the clinical management of memory deficits in patients with Multiple Sclerosis.

Dataset Information

The BDNF Val66Met Polymorphism (rs6265) Modulates Inflammation and Neurodegeneration in the Early Phases of Multiple Sclerosis.

Publications

The BDNF Val66Met Polymorphism (rs6265) Modulates Inflammation and Neurodegeneration in the Early Phases of Multiple Sclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets