Journal
NEUROTOXICITY RESEARCH
Volume 25, Issue 4, Pages 335-347Publisher
SPRINGER
DOI: 10.1007/s12640-013-9437-9
Keywords
Amyloid; BDNF; PPAR-gamma; Apoptosis; Mitochondria
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Funding
- Indian Council of Medical Research (ICMR), New Delhi
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Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have been reported to provide neuroprotective effects against neurodegenerative diseases. The current study was carried out to investigate the effects of chronic administration of pioglitazone, a PPAR-gamma agonist, on cognitive impairment in an animal model of Alzheimer's disease induced by beta-amyloid. Wistar rats received intracerebroventricular (ICV) beta-amyloid (beta A) application (3 nmol/3 mu L), and behavioral alterations (locomotor activity and memory performance) were assessed. Animals were sacrificed immediately following the last behavioral session, and their brains were removed and dissected. Mitochondrial enzymes, oxidative parameters, inflammatory mediators (TNF-alpha, IL-6), caspase activity, and BDNF levels were measured in the hippocampus. ICV beta A-treated rats showed a memory deficit and significantly decreased BDNF level, simultaneously, increase in mitochondrial oxidative damage and inflammatory mediators in the hippocampus. Memory impairment and oxidative damage were reversed by administration of pioglitazone (15 and 30 mg/kg). Pioglitazone also significantly restored the BDNF level and attenuated the actions of inflammatory markers in ICV beta A-treated rats. However, pretreatment with PPAR-gamma antagonist BADGE (15 mg/kg) with higher dose of pioglitazone significantly reversed its protective action in memory impairment in beta A-treated rats, which indicates the involvement of PPAR-gamma receptors mediating neuroprotective action. These results demonstrate that pioglitazone offers protection against beta-amyloid-induced memory dysfunction possibly due to its antioxidant, anti-inflammatory, anti-apoptotic action and neurogenesis-like effect therefore, could have a therapeutic potential in Alzheimer's disease.
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