Deletion of galectin‐3 exacerbates microglial activation and accelerates disease progression and demise in a SOD1G93A mouse model of amyotrophic lateral sclerosis

• DOI: 10.1002/brb3.75
• Publication Date: 2012-07-23T07:21:13Z
• Authors: Bruce J. Lerman; Eric P. Hoffman; Margaret L. Suthe...; Khaled Bouri; Daniel K. Hsu; Fu‐Tong Liu; Jeffrey D. Rothstein; Susan M. Knoblach
• Keywords: Galectin; Galectin-3

Galectins are pleiotropic carbohydrate-binding lectins involved in inflammation, growth/differentiation, and tissue remodeling. The functional role of galectins amyotrophic lateral sclerosis (ALS) is unknown. Expression studies revealed increases galectin-1 mRNA protein spinal cords from SOD1(G93A) mice, galectin-3 -9 mRNAs proteins both mice sporadic ALS patients. As the increase appeared early presymptomatic stages increased progressively through to end stage disease mouse, it was selected for additional study, where found be mainly expressed by microglia. Galectin-3 antagonists not selective do readily cross blood-brain barrier; therefore, we generated SOD1(G93A)/Gal-3(-/-) transgenic evaluate deletion a widely used mouse model ALS. Disease progression, neurological symptoms, survival, inflammation were assessed determine effect on phenotype. did change onset, but resulted more rapid progression functionally defined stages, severely impaired symptoms at all disease, expiration, average, 25 days earlier than SOD1(G93A)/Gal-3(+/+) cohorts. In addition, microglial staining, as well TNF-α, oxidative injury compared with These data support an important neuroinflammation during chronic neurodegenerative disease. We suggest that elevations microglia progresses may represent protective, anti-inflammatory innate immune response motor neuron degeneration.