First description of enhanced expression of transforming growth factor-alpha and glia maturation factor-beta correlate with severity of neuropathology in border disease virus-infected small ruminants.

Border disease is caused by Pestivirus and is characterized by severe neuropathology, and histopathologically observed severe hypomyelination. We have previously shown that small ruminants infected with BDV play an important role for neuropathology and pathogenesis of severe oxidative damage in brain tissue, neural mtDNA; in the production of pathologic levels of nitric oxide; in glial cell activation and stimulation of intrinsic apoptosis pathway. This study aimed to investigate the relationship between glia maturation factor beta (GMF-β) and transforming growth factor alpha (TGF-α) expressions and the causes of BDV-induced neuropathology and to investigate their role in neuropathogenesis in a way that was not presented before. Expression levels of GMF-β and TGF-α were investigated. Results of the study revealed that the levels of GMF-β (P < 0.005) and TGF-α (P < 0.005) expression in the brain tissue markedly increased in the BDV-infected animals compared to the non-infected healthy control group. While TGF-α expressions were predominantly observed in neurons, GMF-β expressions were found in astrocytes, glial cells and neurons. These results were reasonable to suggest that BDV-mediated increased GMF-β might play a pivotal role neuropathogenesis and a different type of role in the mechanism of neurodegeneration/neuropathology in the process of BD. The results also indicated that increased levels of GMF up-regulation in glial cells and neurons causes neuronal destruction, suggesting pathological pathway involving GMF-mediated brain cell cytotoxicity. It is clearly indicated that the cause of astrogliosis is due to severe TGF-a expression. This is the first study to demonstrate the expression of GMF-β and TGF-α in neurons and reactive glial cells and its association with neuropathology in BD.