title: Targeted Antioxidant, Catalase-SKL, Reduces Beta-Amyloid Toxicity in the Rat Brain.
abstract: Accumulation of beta-amyloid (Aβ) in the brain has been implicated as a major contributor to the cellular pathology and cognitive impairment observed in Alzheimer's disease. Beta-amyloid may exert its toxic effects by increasing reactive oxygen species and neuroinflammation in the brain. This study set out to investigate whether a genetically engineered derivative of the peroxisomal antioxidant enzyme catalase (CAT-SKL), is able to reduce the toxicity induced by intracerebroventricular injection of Aβ25-35in the mature rat brain. Histopathological and immunohistochemical analyses were used to evaluate neuroinflammation, and neuronal loss. Spatial learning and reference memory was assessed using the Morris water maze. CAT-SKL treatment was able to reduce the pathology induced by Aβ25-35toxicity by significantly decreasing microglia activation in the basal forebrain and thalamus, and reducing cholinergic loss in the basal forebrain. Aβ25-35animals showed deficits in long-term reference memory in the Morris water maze, while Aβ25-35animals treated with CAT-SKL did not demonstrate long-term memory impairments. This preclinical data provides support for the use of CAT-SKL in reducing neuroinflammation and long-term reference memory deficits induced by Aβ25-35.
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, N6A 5C1, Canada.
authors.forename: Hayley J
authors.initials: HJ
authors.lastname: Nell
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, N6A 5C1, Canada.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Au
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, 48201.
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Giordano
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, 48201.
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Terlecky
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, N6A 5C1, Canada.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Walton
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, N6A 5C1, Canada.
authors.forename: Shawn N
authors.initials: SN
authors.lastname: Whitehead
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, N6A 5C1, Canada.
authors.forename: David F
authors.initials: DF
authors.lastname: Cechetto
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001921:Brain / Q000201:enzymology; D002374:Catalase / Q000032:analysis; D016923:Cell Death; D004353:Drug Evaluation, Preclinical; D007859:Learning Disabilities / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000188:drug therapy / Q000517:prevention & control; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000633:toxicity*; D016548:Prosencephalon / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D065853:Spatial Learning / Q000187:drug effects; D013788:Thalamus / Q000737:chemistry / Q000187:drug effects / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D002374:Catalase; C000626312:catalase-SKL, rat
keywords: beta amyloid; catalase; neuroinflammation; oxidative stress