The role of dorsal root ganglia activation and brain‐derived neurotrophic factor in multiple sclerosis

• Published in: Journal of cellular and molecular medicine 2012-08, Vol.16 (8), p.1856-1865
• Main Authors: Zhu, Wenjun, Frost, Emma E., Begum, Farhana, Vora, Parvez, Au, Kelvin, Gong, Yuewen, MacNeil, Brian, Pillai, Prakash, Namaka, Mike
• Format: Article
• Language: English
• Subjects: Animals; Anterograde transport; Antibodies; Autoimmune diseases; BDNF; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Copolymer 1; Demyelination; Disability Evaluation; Dorsal horn; Dorsal root ganglia; DRG; EAE; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - pathology; Enzyme-Linked Immunosorbent Assay; Experimental allergic encephalomyelitis; Female; Ganglia, Spinal - metabolism; Ganglia, Spinal - pathology; Gene expression; Gene Expression Regulation; Immunohistochemistry; Inflammation; Lumbar Vertebrae - metabolism; Lumbar Vertebrae - pathology; Multiple sclerosis; Multiple Sclerosis - metabolism; Multiple Sclerosis - pathology; Myelin; Neurological complications; Neuroprotection; Original; Paralysis; Polymerase chain reaction; Protein expression; Protein transport; Proteins; Rats; Rats, Inbred Lew; RNA transport; Spinal cord; Statistical analysis; Substantia alba; Tumor necrosis factor-TNF; Variance analysis
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/j.1582-4934.2011.01481.x

Multiple sclerosis (MS) is characterized by focal destruction of the white matter of the brain and spinal cord. The exact mechanisms underlying the pathophysiology of the disease are unknown. Many studies have shown that MS is predominantly an autoimmune disease with an inflammatory phase followed by a demyelinating phase. Recent studies alongside current treatment strategies, including glatiramer acetate, have revealed a potential role for brain‐derived neurotrophic factor (BDNF) in MS. However, the exact role of BDNF is not fully understood. We used the experimental autoimmune encephalomyelitis (EAE) model of MS in adolescent female Lewis rats to identify the role of BDNF in disease progression. Dorsal root ganglia (DRG) and spinal cords were harvested for protein and gene expression analysis every 3 days post‐disease induction (pdi) up to 15 days. We show significant increases in BDNF protein and gene expression in the DRG of EAE animals at 12 dpi, which correlates with peak neurological disability. BDNF protein expression in the spinal cord was significantly increased at 12 dpi, and maintained at 15 dpi. However, there was no significant change in mRNA levels. We show evidence for the anterograde transport of BDNF protein from the DRG to the dorsal horn of the spinal cord via the dorsal roots. Increased levels of BDNF within the DRG and spinal cord in EAE may facilitate myelin repair and neuroprotection in the CNS. The anterograde transport of DRG‐derived BDNF to the spinal cord may have potential implications in facilitating central myelin repair and neuroprotection.