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dc.contributor.authorPatnaik R.
dc.contributor.authorSharma A.
dc.contributor.authorSkaper S.D.
dc.contributor.authorMuresanu D.F.
dc.contributor.authorLafuente J.V.
dc.contributor.authorCastellani R.J.
dc.contributor.authorNozari A.
dc.contributor.authorSharma H.S.
dc.date.accessioned2020-09-02T22:25:25Z
dc.date.available2020-09-02T22:25:25Z
dc.date.issued2018
dc.identifier10.1007/s12035-017-0743-8
dc.identifier.citation55, 1, 312-321
dc.identifier.issn08937648
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5766
dc.descriptionAlzheimer’s disease (AD) is one of the leading causes for disability and death affecting millions of people worldwide. Thus, novel therapeutic strategies are needed to reduce brain pathology associated with AD. In view of increasing awareness regarding involvement of histaminergic pathways in AD, we explored the role of one H3 receptor inverse agonist BF 2649 and one selective H3 receptor antagonist with partial H4 agonist activity in amyloid beta peptide (AβP) infusion-induced brain pathology in a rat model. AD-like pathology was produced by administering AβP (1–40) intracerebroventricular (i.c.v.) in the left lateral ventricle (250 ng/10 μl, once daily) for 4 weeks. Control rats received saline. In separate group of rats, either BF 2649 (1 mg/kg, i.p.) or clobenpropit (1 mg/kg, i.p.) was administered once daily for 1 week after 3 weeks of AβP administration. After 30 days, blood-brain barrier (BBB) breakdown, edema formation, neuronal, glial injuries, and AβP deposits were examined in the brain. A significant reduction in AβP deposits along with marked reduction in neuronal or glial reactions was seen in the drug-treated group. The BBB breakdown to Evans blue albumin and radioiodine in the cortex, hippocampus, hypothalamus, and cerebellum was also significantly reduced in these drug-treated groups. Clobenpropit showed superior effects than the BF2649 in reducing brain pathology in AD. Taken together, our observations are the first to show that blockade of H3 and stimulation of H4 receptors are beneficial for the treatment of AD pathology, not reported earlier. © Springer Science+Business Media New York 2016.
dc.language.isoen
dc.publisherHumana Press Inc.
dc.subjectAlzheimer’s disease (AD)
dc.subjectAmyloid beta peptide (AβP)
dc.subjectBF2649
dc.subjectBlood-brain barrier
dc.subjectBrain pathology
dc.subjectClobenpropit
dc.subjectH3 receptor inverse agonist
dc.subjectH3 receptors antagonist with partial H4 agonist
dc.subjectHistamine
dc.subjectalbumin
dc.subjectamyloid beta protein[1-40]
dc.subjectbf 2649
dc.subjectclobenpropit
dc.subjectglial fibrillary acidic protein
dc.subjecthistamine H3 receptor agonist
dc.subjectradioactive iodine
dc.subjectunclassified drug
dc.subjectamyloid beta protein
dc.subjectclobenpropit
dc.subjecthistamine agonist
dc.subjecthistamine H3 receptor antagonist
dc.subjecthistamine H4 receptor
dc.subjectHrh4 protein, rat
dc.subjectimidazole derivative
dc.subjectthiourea
dc.subjectAlzheimer disease
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectblood brain barrier
dc.subjectbrain cortex
dc.subjectbrain edema
dc.subjectbrain nerve cell
dc.subjectcell damage
dc.subjectcerebellum
dc.subjectcontrolled study
dc.subjectdrug effect
dc.subjectglia cell
dc.subjecthippocampus
dc.subjecthistopathology
dc.subjecthypothalamus
dc.subjectimmunohistochemistry
dc.subjectlateral brain ventricle
dc.subjectmale
dc.subjectnonhuman
dc.subjectrat
dc.subjectagonists
dc.subjectAlzheimer disease
dc.subjectanalogs and derivatives
dc.subjectanimal
dc.subjectbrain
dc.subjectchemically induced
dc.subjectinverse agonism
dc.subjectpartial agonism
dc.subjectpathology
dc.subjectSprague Dawley rat
dc.subjectAlzheimer Disease
dc.subjectAmyloid beta-Peptides
dc.subjectAnimals
dc.subjectBrain
dc.subjectDrug Inverse Agonism
dc.subjectDrug Partial Agonism
dc.subjectHistamine Agonists
dc.subjectHistamine H3 Antagonists
dc.subjectImidazoles
dc.subjectMale
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectReceptors, Histamine H4
dc.subjectThiourea
dc.titleHistamine H3 inverse agonist BF 2649 or antagonist with partial h4 agonist activity clobenpropit reduces amyloid beta peptide-induced brain pathology in alzheimer’s disease
dc.typeArticle


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