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Effects of GLP-1 analogue, liraglutide on inflammation, stem cell proliferation, differentiation and cognition in mouse brain

Alzheimer's disease (AD) is the most common form of dementia in the elderly and is characterized as a 'progressive neurodegenerative disorder' with neuronal amyloid deposition and impaired cognitive function. Impaired insulin signaling is one of the many similarities between AD and type 2 diabetes. Currently no effective treatment is on the market for AD and hence novel therapeutic strategies are needed. In this study, effects of GLP-l analogue, liraglutide on neuroinflammation, stem cell proliferation, differentiation and cognition were investigated. Chronic treatment of liraglutide enhanced neurogenesis in 3, 6, 12, 15 months old APP IPS 1 mice and exerted beneficial effects on different pathological hallmarks (amyloid and dense core plaque, neurogenesis, synaptic density and inflammation) in 7 months old APP/PS 1 mice. Liraglutide administration reduced mean activated microglia load, reactive astrocyte load, cytokines and nitrite levels in the brains of mouse model of neuroinflammation (irradiated mouse brain) indicating that liraglutide has direct role in reducing neuroinflammation. Liraglutide also increased the stem cell pool, progenitor cell proliferation and differentiation, enhanced LTP, recognition memory in irradiated mouse brain. These observations highlight the immense potential of liraglutide as a therapeutic agent for the treatment of neurodegenerative disorders such as Alzheimer's disease.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:674740
Date January 2013
CreatorsParthsarathy, Vadivel
PublisherUlster University
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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