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Neurotoxicity Research

, Volume 25, Issue 4, pp 335–347 | Cite as

Role of Nuclear Receptor on Regulation of BDNF and Neuroinflammation in Hippocampus of β-Amyloid Animal Model of Alzheimer’s Disease

  • Atish PrakashEmail author
  • Anil Kumar
Original Article

Abstract

Peroxisome proliferator-activated receptor-γ (PPAR-γ) 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-γ agonist, on cognitive impairment in an animal model of Alzheimer’s disease induced by β-amyloid. Wistar rats received intracerebroventricular (ICV) β-amyloid (βA) application (3 nmol/3 μL), 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-α, IL-6), caspase activity, and BDNF levels were measured in the hippocampus. ICV βA-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 βA-treated rats. However, pretreatment with PPAR-γ antagonist BADGE (15 mg/kg) with higher dose of pioglitazone significantly reversed its protective action in memory impairment in βA-treated rats, which indicates the involvement of PPAR-γ receptors mediating neuroprotective action. These results demonstrate that pioglitazone offers protection against β-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.

Keywords

Amyloid BDNF PPAR-γ Apoptosis Mitochondria 

Notes

Acknowledgments

Authors are thankful to the financial support of Indian Council of Medical Research (ICMR), New Delhi for carrying out this work.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Pharmacology DivisionUniversity Institute of Pharmaceutical Sciences, Panjab UniversityChandigarhIndia
  2. 2.Pharmacology DivisionIndo Soviet College of PharmacyMogaIndia

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