RESUMO
Introduction: The effect of brain-derived neurotrophic factor (BDNF) on the modulation of metabolic processes in the liver is poorly understood. Therefore, the aim of this study was to investigate whether hepatic concentrations or activities of metabolic biomarkers depend on altered BDNF/TrkB content in the liver, resulting from different BDNF genotypes of rats. In addition, it was assessed whether 5-week moderate endurance training modifies the levels of BDNF/Trk-B signaling and studied hepatic markers. Methods: Experiments were performed on wild-type and heterozygous BDNF knockout (HET, SD-Bdnf) rats, which were divided into four groups: control with normal genotype (Bdnf+/+), control with BDNF knockout genotype (Bdnf+/-), trained with normal genotype (Bdnf+/+T) and trained with BDNF knockout genotype (Bdnf +/-T). BDNF/TrkB concentrations as well as selected metabolic biomarkers including lipids-total cholesterol (CHOL), low-density lipoprotein (LDL), triglycerides (TG); enzymes-alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP); hormones-insulin (INS) and leptin (LEPT) as well as interleukin-6 (IL-6) as regeneration indicator were measured directly in liver homogenates. Results and Discussion: The study showed that Bdnf+/- rats exhibited reduced BDNF/TrkB signaling (BDNF, p < 0.0001; Trk-B, p = 0.0005), altered lipid levels (CHOL, p < 0.0001; LDL, p < 0.0001; TG, p = 0.0006) and reduced hepatic ALAT (p = 0.0004) and GGT (p < 0.0001) activity, which may contribute to hepatic steatosis and obesity, as well as indicate impairment of specific metabolic pathways in the liver. Interestingly, endurance training did not alter hepatic BDNF and TrkB content, but improved ALAT (p = 0.0366) and ASAT (p = 0.0191) activities and increased hepatic IL-6 (p = 0.0422) levels in Bdnf +/- rats, suggesting enhanced liver regeneration in animals with BDNF allele loss.
RESUMO
The purpose of this study was to determine whether altered serum and/or muscle concentrations of brain-derived neurotrophic factor (BDNF) can modify the electrophysiological properties of spinal motoneurons (MNs). This study was conducted in wild-type and Bdnf heterozygous knockout rats (HET, SD-BDNF). Rats were divided into four groups: control, knockout, control trained, and knockout trained. The latter two groups underwent moderate-intensity endurance training to increase BDNF levels in serum and/or hindlimb muscles. BDNF and other neurotrophic factors (NFs), including glial cell-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), nerve growth factor (NGF), and neurotrophin-4 (NT-4) were assessed in serum and three hindlimb muscles: the tibialis anterior (TA), medial gastrocnemius (MG), and soleus (Sol). The concentrations of tropomyosin kinase receptor B (Trk-B), interleukin-15 (IL-15), and myoglobin (MYO/MB) were also evaluated in these muscles. The electrophysiological properties of lumbar MNs were studied in vivo using whole-cell current-clamp recordings. Bdnf knockout rats had reduced levels of all studied NFs in serum but not in hindlimb muscles. Interestingly, decreased serum NF levels did not influence the electrophysiological properties of spinal MNs. Additionally, endurance training did not change the serum concentrations of any of the NFs tested but significantly increased BDNF and GDNF levels in the TA and MG muscles in both trained groups. Furthermore, the excitability of fast MNs was reduced in both groups of trained rats. Thus, changes in muscle (but not serum) concentrations of BDNF and GDNF may be critical factors that modify the excitability of spinal MNs after intense physical activity.