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Reducing inflammation and rescuing FTD-related behavioral deficits in progranulin-deficient mice with alpha 7 nicotinic acetylcholine receptor agonists
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Rekke forfattare: 102015 (engelsk)Inngår i: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 97, nr 4, s. 454-462Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Mutations in the progranulin gene cause frontotemporal dementia (FTD), a debilitating neurodegenerative disease that involves atrophy of the frontal and temporal lobes and affects personality, behavior, and language. Progranulin-deficient mouse models of FTD exhibit deficits in compulsive and social behaviors reminiscent of patients with FTD, and develop excessive microgliosis and increased release of inflammatory cytokines. Activation of nicotinic acetylcholine receptors (nAChRs) by nicotine or specific alpha 7 nAChR agonists reduces neuroinflammation. Here, we investigated whether activation of nAChRs by nicotine or alpha 7 agonists improved the excessive inflammatory and behavioral phenotypes of a progranulin-deficient FTD mouse model. We found that treatment with selective alpha 7 agonists, PHA-568487 or ABT-107, strongly suppressed the activation of NF-kappa B in progranulin-deficient cells. Treatment with ABT-107 also reduced microgliosis, decreased TNF alpha levels, and reduced compulsive behavior in progranulin-deficient mice. Collectively, these data suggest that targeting activation of the alpha 7 nAChR pathway may be beneficial in decreasing neuroinflammation and reversing some of the behavioral deficits observed in progranulin-deficient FTD.

sted, utgiver, år, opplag, sider
2015. Vol. 97, nr 4, s. 454-462
Emneord [en]
Frontotemporal dementia, Progranulin, Nicotine, Inflammation, Microglial activation
HSV kategori
Identifikatorer
URN: urn:nbn:se:su:diva-159638DOI: 10.1016/j.bcp.2015.07.016ISI: 000363437200012PubMedID: 26206194OAI: oai:DiVA.org:su-159638DiVA, id: diva2:1245443
Tilgjengelig fra: 2018-09-05 Laget: 2018-09-05 Sist oppdatert: 2018-09-05bibliografisk kontrollert

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