The role of microglial PARP-1 in Alzheimer’s disease

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dc.contributor.authorRezaeian Mehrabadi, Abbas
dc.contributor.examiningcommitteeMiller, Donald (Pharmacology and Therapeutics) Jackson, Michael (Pharmacology and Therapeutics) Karimi, Soheila (Physiology & Pathophysiology)en_US
dc.contributor.supervisorKauppinen, Tiina (Pharmacology and Therapeutics)en_US
dc.date.accessioned2018-01-03T16:52:32Z
dc.date.available2018-01-03T16:52:32Z
dc.date.issued2017-04en_US
dc.degree.disciplinePharmacology and Therapeuticsen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractAlzheimer’s disease (AD) is a neurodegenerative disorder with profound chronic neuroinflammation. Our previous studies have identified poly(ADP-ribose) polymerase-1 (PARP-1) as a key driver of microglial pro-inflammatory functions. Here we tested a hypothesis that microglial PARP-1-mediated pro-inflammatory activation can affect AD disease progression (in vivo) and directly disrupt blood-brain barrier integrity (in vitro). The cognitive functions in AD and WT mice were assessed by behavioral test. The brain tissue was analyzed by immunocytochemistry and cultured endothelial cells were analyzed for tight junction proteins expression and permeability assays. Microglial constitutive PARP-1 activation induced cognitive impairments in WT and AD mice, changed microglial morphology, increased their number and intensity and induced astrogliosis. NO and TNFα that released by Aβ-induced microglia reduced the expression of tight junction proteins and increased paracellular permeability in endothelial cells. In Conclusion, our data demonstrate that microglial continuous PARP-1 activation can directly drive AD pathology and progression.en_US
dc.description.noteFebruary 2018en_US
dc.identifier.urihttp://hdl.handle.net/1993/32727
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsopen accessen_US
dc.subjectAlzheimer' Diseaseen_US
dc.subjectMicrogliaen_US
dc.subjectPARP-1en_US
dc.titleThe role of microglial PARP-1 in Alzheimer’s diseaseen_US
dc.typemaster thesisen_US
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