Targeted Antioxidant, Catalase-SKL, Reduces Beta-Amyloid Toxicity in the Rat Brain
| Autor: | Stanley R. Terlecky, Shawn N. Whitehead, David F. Cechetto, Jennifer. L. Au, Paul A. Walton, Courtney R. Giordano, Hayley J. Nell |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cellular pathology Basal forebrain Microglia business.industry General Neuroscience Morris water navigation task Pharmacology medicine.disease_cause Pathology and Forensic Medicine 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Toxicity medicine Cholinergic Neurology (clinical) business Neuroscience 030217 neurology & neurosurgery Neuroinflammation Oxidative stress |
| Zdroj: | Brain Pathology. 27:86-94 |
| ISSN: | 1015-6305 |
| Popis: | 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 Aβ25-35 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 Aβ25-35 toxicity by significantly decreasing microglia activation in the basal forebrain and thalamus, and reducing cholinergic loss in the basal forebrain. Aβ25-35 animals showed deficits in long-term reference memory in the Morris water maze, while Aβ25-35 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 Aβ25-35. |
| Databáze: | OpenAIRE |
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