Analysis of Chemokines and Receptors Expression Profile in the Myelin Mutant Taiep Rat

Soto-Rodriguez, Guadalupe; Gonzalez-Barrios, Juan-Antonio; Martinez-Fong, Daniel; Blanco-Alvarez, Victor-Manuel; Eguibar, Jose R.; Ugarte, Araceli; Martinez-Perez, Francisco; Brambila, Eduardo; Millán-Perez Peña, Lourdes; Pazos-Salazar, Nidia-Gary; Torres-Soto, Maricela; Garcia-Robles, Guadalupe; Tomas-Sanchez, Constantino; Leon-Chavez, Bertha Alicia

Results obtained in this work support the idea that the taiep rat exhibits a chronic neuroinflammatory profile that Oxidative Medicine and Cellular Longevity is different from other models of demyelination such as EAE. The major differences of taiep rats in comparison with EAE are that cytokines such as IFN-, TNF-, and IL-6 were unaltered but IL-1 and IL-10 were downregulated in 1-month-old taiep rats. In normal pups, the exposure to stress stimuli leads to decreased levels of IL-10 and IL-1 in serum [26] . Downregulation of IL-1 and IL-10 in the brainstem of taiep rats might be explained in part by the motor alterations of taiep mother and pups, acting as a stress stimulus. In addition, downregulation of TGF-1 was found in taiep rats. As TGF-1 suppresses inflammation and promotes neuronal survival in adult CNS, the lack of these effects could be associated with the increased neuronal apoptosis and necrosis in the brain of adult taiep rats [5] . The decrease in TGF-1 expression at 6-month-old taiep and SD rats might also be a sign of CNS aging. We found that GPR17 was downregulated in the taiep rats. This G coupled protein receptor is an important mediator of OPC differentiation and white matter repair that is expressed by a subset of OPCs to operate as an early sensor of brain damage [27] . Accordingly, inhibition of GPR17 expression causes impairment in oligodendrocytes differentiation and myelination in in vivo and in vitro systems [28] . Supporting this, GPR17 downregulation could contribute to alterations in remyelination in the taiep rats. Another coupled protein receptor that was downregulated in the brainstem of 6 Oxidative Medicine and Cellular Longevity 1-month-old taiep rats was FPR1 (formyl peptide receptor 1), which mediates the chemotaxis, activation, and cytokine gene transcription in phagocytic leucocytes in response to bacterial formylated chemotactic peptides [29] . These findings suggest that the immune response is decreased in the taiep rat, producing a predominant chronic neuroinflammatory process or astrocyte priming as was reported previously in cell culture [3] .