Neurotrophins, cytokines, oxidative parameters and funcionality in Progressive Muscular Dystrophies

Abstract

We investigated the levels of brain derived-neurotrophic factor (BDNF), cytokines and oxidative parameters in serum and tried to correlate them with the age and functionality of patients with Progressive Muscle Dystrophies (PMD). The patients were separated into six groups (case and controls pared by age and gender), as follows: Duchenne Muscular Dystrophy (DMD); Steinert Myotonic Dystrophy (SMD); and Limb-girdle Muscular Dystrophy type-2A (LGMD2A). DMD patients (±17.9 years old) had a decrease of functionality, an increase in the IL-1β and TNF-α levels and a decrease of IL-10 levels and superoxide dismutase activity in serum. SMD patients (±25.8 years old) had a decrease of BDNF and IL-10 levels and superoxide dismutase activity and an increase of IL-1β levels in serum.LGMD2A patients (±27.7 years old) had an decrease only in serum levels of IL-10. This research showed the first evidence of BDNF involvement in the SMD patients and a possible unbalance between pro-inflammatory and anti-inflammatory cytokine levels, along with decreased superoxide dismutase activity in serum of DMD and SMD patients.

Cardiovascular Disease in Duchenne Muscular Dystrophy

“…BDNF is a neuronal growth and survival factor, and plasma levels have been shown to correlate with cardiovascular risk in general 113 and specifically LV ejection fraction (LVEF) in DMD patients. 114 , 115 In DMD animal models, polymorphisms within the BDNF gene lead to reduced BDNF metabolism into the active form, alteration in cardiac-specific gene expression, and reduced cardiomyocyte contractility. 37 BDNF acts primarily by binding to the tyrosine kinase B (TrkB) receptor, leading to autophosphorylation of the receptor and downstream activation of several signaling pathways, including MAPK, the phospholipase C-gamma (PLC-γ), and the phosphatidylinositol 3-kinase (PI3K).…”

Redox imbalance in peripheral blood of type 1 myotonic dystrophy patients

“…Decreased levels of antioxidant enzymes in blood samples from DM1 patients, including decreased SOD, have also been reported. 23 In contrast, earlier reports showed increased SOD1 activity. 5 These latter activities were measured in blood serum and could have been a reflection of erythrocyte lysis, or other interfering substances.…”

Late Brain Involvement after Neonatal Immune Activation

“…The absorbance was read on a plate reader at 492 nm wavelength (EMax, Molecular Devices, Minneapolis, MN, USA). Total protein was measured using bovine serum albumin as a standard as described in the literature [24].…”