Sensory and Motor Systems
Author: Georgina Oriana Mingolo Malnati | email: georginamingolo@gmail.com
Georgina Oriana Mingolo Malnati 1°, Mayra Micaela Montes 1°, Libia Catalina Salinas Castellanos 1°, María Natalia Gobetto 1°, Osvaldo Daniel Uchitel 1°, Carina Weissmann 1°
1° IFIBYNE
Neuropathic pain is a key feature of ?-galactosidase A (Gla) deficient Fabry Disease (FD). Ion channels play an important role at each step in the pain pathway. Ion channels affect the sensation of pain by modulating the excitability of specialized neurons in the pain pathway (Xie, 2007). Acid-sensing ion channels (ASICs) are sensors involved in neural modulation in the central nervous system and pain-associated tissue acidosis in the peripheral system. Upregulation of ASIC1 was documented in many pathological conditions. Our previous results in cell cultures showed that the incorporation of Gb3 led to the upregulation of ASIC1a. In this work, we analyzed the Gla knockout mouse (GlaKO) (Ohshima et al.,1997) model that accumulates Gb3. We detected higher levels of ASIC1 at the Anterior Cingulate Cortex (ACC), spinal cord (SC) and Dorsal root ganglia (DRG) in the Glako mice. We subdivided the analysis in lumbar, thoracic and cervical regions. The increase for SC and DRGs was greater at lumbar regions. Also, we compared the expression of ASIC1 at 4 and 8 months and in male and female mice. We detected higher expression levels in older mice as well as in female mice. In all cases, the increase was accompanied by higher levels of ERK phosphorylation. This work confirms the results obtained in cell lines and points at altered channel levels in the pain pathway, signaling pathways involved, and ASIC1 as a potential target to analyze in the model for future therapies in pain in FD.