| First Author | Hirose M | Year | 2020 |
| Journal | Neurosci Res | PubMed ID | 33316302 |
| Mgi Jnum | J:302982 | Mgi Id | MGI:6510663 |
| Doi | 10.1016/j.neures.2020.10.006 | Citation | Hirose M, et al. (2020) Stagnation of glymphatic interstitial fluid flow and delay in waste clearance in the SOD1-G93A mouse model of ALS. Neurosci Res |
| abstractText | Overexpression and mislocalization of aquaporin-4 (AQP4) in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis (ALS) have previously been reported. However, how alterations of AQP4 affect interstitial bulk flow in the brain and spinal cord, the so-called glymphatic system, is unclear. Here, we report an enhanced accumulation of disease-associated SOD1 species including SOD1 oligomers in SOD1(G93A);AQP4(-/-) mice compared with SOD1(G93A) mice during ALS disease progression, as analyzed by sandwich ELISA. By directly injecting SOD1 oligomers into the spinal cord parenchyma, we observed a significantly larger delay in clearance of biotinylated or fluorescent-labeled SOD1 oligomers in AQP4(-/-) mice than in wild-type mice. Furthermore, when we injected the fluorescent-labeled tracer protein ovalbumin into the cisterna magna and analyzed the tracer distribution in the cervical spinal cord, approximately 35 % processing ability was found to be reduced in SOD1(G93A) mice compared to wild-type mice. These results suggest that the glymphatic system is abnormal and that waste clearance is delayed in SOD1(G93A) mice. |
