MMP-2 and MMP-9 are elevated in spinal cord and skin in a mouse model of ALS

We aimed to clarify the role of matrix metalloproteinases (MMP) as a possible link between neurodegeneration and skin pathology in ALS by determination of gelatinase MMP-2 and MMP-9 in spinal cord and skin of transgenic SOD1(G93A) mice. To elucidate mechanisms influencing MMPs, markers of oxidative damage (malondialdehyde (MDA), 3-nitrotyrosine (3-NT) and 8-hydroxy-2′-deoxyguanosine (8OH2′dG)) as well as cytokines (tumor necrosis factor alpha (TNF-α) and interleukin 1ß (IL-1ß)) were determined. We measured MMP-9, MMP-2, 3-NT, TNF-α, and IL-1ß using ELISA, MDA using High Performance Liquid Chromatography (HPLC) and 8OH2′dG using HPLC with electrochemical detection (HPLC-ECD) in SOD1 and WT. MMP-9 was elevated in spinal cord and skin of SOD1 at 90 days (p = 0.009, p < 0.001) and 120 days (p < 0.01, p = 0.04). MMP-2 was elevated in the spinal cord at 90 days (p = 0.01) and in the skin at 120 days (p = 0.039). We observed a correlation of MMP-9 in spinal cord and skin of SOD1 (p = 0.04). MDA was elevated in the spinal cord of SOD1 at 90 and 120 days (p = 0.00006, p = 0.01) and 8OH2′dG at 90 days (p = 0.048). IL-1ß was elevated in the spinal cord of SOD1 at 120 days (p = 0.02). Our data confirms that gelatinase MMPs are a common factor linking neurodegeneration and skin changes in ALS. It suggests that oxidative stress and microglial-derived cytokines contribute to the elevation of gelatinase MMPs especially in later stages of disease. Our data raises the question whether the skin may function as a biomarker for specific aspects of disease pathology in ALS.