Brain-Derived Neurotrophic Factor Levels are Lower in Chronic Stroke Patients: A Relation with Manganese-dependent Superoxide Dismutase ALA16VAL Single Nucleotide Polymorphism through Tumor Necrosis Factor-α and Caspases Pathways

J Stroke Cerebrovasc Dis. 2018 Nov;27(11):3020-3029. doi: 10.1016/j.jstrokecerebrovasdis.2018.06.032. Epub 2018 Aug 25.

Abstract

The manganese-dependent superoxide dismutase (MnSOD) Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of vascular diseases. Brain-Derived Neurotrophic Factor (BDNF) plays an essential role in the plasticity and neuronal regeneration of the brain after vascular injuries. However, little is known about interaction between MnSOD Ala16Val SNP on stroke, a frequent neurologic disease that involves various interacting pathways, such as vascular dysfunctions, inflammation, and neurotrophic factors. In this sense, the objective of this study was to investigate the relationship between MnSOD Ala16Val SNP with BDNF levels on stroke and also its influence on nitrosative stress, inflammatory, apoptotic, and DNA damage parameters. For this, 88 subjects were investigated, 44 subjects poststroke and 44 healthy controls. Questionnaires were applied to clinical characteristics and after laboratorial exams were collected. We analyzed levels of oxidative/nitrosative stress, inflammatory, apoptotic, and DNA damage markers. We showed a higher proportion of VV genotype in poststroke as compared to healthy subjects. Nitrite/nitrate, Tumor Necrosis Factor-α, Caspase 3 (CASP 3) and 8 (CASP 8) activation, Acethylcholinesterase (AChE), and Picogreen levels were higher in VV poststroke group, as well as BDNF and ACh levels were lower in VV and AV poststroke. We may suggest that V allele carries a worse outcome profile after stroke, relating to nitrosative stress, inflammatory, and apoptotic response. These events associated to a BDNF reduction, probably, contribute to the appearance or reincidence of stroke.

Keywords: Apoptosis; BDNF; Inflammation; MsSOD Ala16Val polymorphism; Stroke.

MeSH terms

  • Acetylcholinesterase / blood
  • Aged
  • Apoptosis
  • Biomarkers / blood
  • Brain-Derived Neurotrophic Factor / blood*
  • Case-Control Studies
  • Caspase 3 / blood*
  • Caspase 8 / blood*
  • Chronic Disease
  • DNA Damage
  • Down-Regulation
  • Female
  • GPI-Linked Proteins / blood
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation Mediators / blood*
  • Male
  • Middle Aged
  • Nitrates / blood
  • Nitrites / blood
  • Nitrosative Stress
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Stroke / blood*
  • Stroke / diagnosis
  • Stroke / enzymology
  • Stroke / genetics*
  • Superoxide Dismutase / genetics*
  • Tumor Necrosis Factor-alpha / blood*

Substances

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • GPI-Linked Proteins
  • Inflammation Mediators
  • Nitrates
  • Nitrites
  • Tumor Necrosis Factor-alpha
  • BDNF protein, human
  • Superoxide Dismutase
  • superoxide dismutase 2
  • ACHE protein, human
  • Acetylcholinesterase
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8