Open AccessTargeted Antioxidant, Catalase–SKL, Reduces Beta‐Amyloid Toxicity in the Rat Brain
Author(s) -
Nell Hayley J.,
Au Jennifer. L.,
Giordano Courtney R.,
Terlecky Stanley R.,
Walton Paul A.,
Whitehead Shawn N.,
Cechetto David.F.
Publication year - 2017
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12368
Subject(s) - neuroinflammation , morris water navigation task , basal forebrain , amyloid beta , neurotoxicity , toxicity , amyloid (mycology) , microglia , pharmacology , cholinergic , neuroscience , pathology , medicine , biology , hippocampus , inflammation , disease
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 Aβ 25–35 in 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 Aβ 25‐35 toxicity by significantly decreasing microglia activation in the basal forebrain and thalamus, and reducing cholinergic loss in the basal forebrain. Aβ 25–35 animals showed deficits in long‐term reference memory in the Morris water maze, while Aβ 25–35 animals 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 Aβ 25–35.