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Conference Paper: Adiponectin deficiency exacerbated neuropathologenesis and cognitive functions in Alzheimer’s disease mice: potential application of AdipoRon as Alzheimer’s disease treatment

TitleAdiponectin deficiency exacerbated neuropathologenesis and cognitive functions in Alzheimer’s disease mice: potential application of AdipoRon as Alzheimer’s disease treatment
Authors
Issue Date2019
PublisherHong Kong Academy of Medicine Press. The Journal's web site is located at http://www.hkmj.org/
Citation
The 24th Medical Research Conference, Hong Kong, 19 January 2019. In Hong Kong Medical Journal, 2019, v. 25 n. 1, Suppl. 1, p. 35, abstract no. 52 How to Cite?
AbstractIntroduction: Adiponectin (APN) reduces with age and has been implicated in Alzheimer’s disease (AD). Adiponectin has insulin-sensitising and anti-inflammatory abilities. We aimed to study if (i) APN deficiency affects amyloid β (Aβ) deposition, neuroinflammation and cognitive functions in AD mice; (ii) AdipoRon alleviates AD pathologies and cognitive functions in AD mice. Methods: Transgenic mice (5xFAD) carrying familial amyloid precursor protein and presenilin mutations were used in this study. We also generated an adiponectin-deficient AD mice (5xFAD;APN-/-) by crossing 5xFAD with APN-/- mice. These mice were fed with either vehicle or AdipoRon (50 mg/kg bodyweight per day) for 3 months. Cognitive functions of these mice were investigated. Neuropathological and molecular changes in the brains were examined. Results: Adiponectin deficiency in 5xFAD mice exacerbated memory deficits, and AD pathologies. Immunostaining demonstrated that microglia was reactivated but its phagocytic activity to Aβ was reduced in 5xFAD;APN-/- mice. Pro-inflammatory cytokine levels were elevated in the brain. Liquid chromatography–tandem mass spectrometry analysis confirmed that AdipoRon can cross the blood-brain barrier. AdipoRontreated 5xFAD and 5xFAD;APN-/- mice showed reduction of Aβ deposition in the cortex and hippocampus. AdipoRon also reduced generation of other cleavage products in amyloidosis. AdipoRon can suppress neuroinflammation, glial activation and resume the phagocytic activity of microglia. Mice treated with AdipoRon demonstrated increased activation of insulin signalling and insulin sensitisation. Lastly, AdipoRon reversed neuronal and dendritic spines reduction as well as cognitive functions in both 5xFAD and 5xFAD;APN-/- mice. Conclusion: In summary, our results demonstrated that APN deficiency exacerbated AD pathologies and neurodegeneration. Oral administration of AdipoRon can reverse cognitive impairments and AD pathologies by insulin sensitisation, demonstrating its therapeutic potential to treat AD.
DescriptionOrganizer: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
Persistent Identifierhttp://hdl.handle.net/10722/276244
ISSN
2017 Impact Factor: 1.226
2015 SCImago Journal Rankings: 0.279

 

DC FieldValueLanguage
dc.contributor.authorNg, CL-
dc.contributor.authorJian, M-
dc.contributor.authorBunting, M-
dc.contributor.authorMa, KFO-
dc.contributor.authorChung, SK-
dc.contributor.authorChan, KH-
dc.date.accessioned2019-09-10T02:58:56Z-
dc.date.available2019-09-10T02:58:56Z-
dc.date.issued2019-
dc.identifier.citationThe 24th Medical Research Conference, Hong Kong, 19 January 2019. In Hong Kong Medical Journal, 2019, v. 25 n. 1, Suppl. 1, p. 35, abstract no. 52-
dc.identifier.issn1024-2708-
dc.identifier.urihttp://hdl.handle.net/10722/276244-
dc.descriptionOrganizer: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong-
dc.description.abstractIntroduction: Adiponectin (APN) reduces with age and has been implicated in Alzheimer’s disease (AD). Adiponectin has insulin-sensitising and anti-inflammatory abilities. We aimed to study if (i) APN deficiency affects amyloid β (Aβ) deposition, neuroinflammation and cognitive functions in AD mice; (ii) AdipoRon alleviates AD pathologies and cognitive functions in AD mice. Methods: Transgenic mice (5xFAD) carrying familial amyloid precursor protein and presenilin mutations were used in this study. We also generated an adiponectin-deficient AD mice (5xFAD;APN-/-) by crossing 5xFAD with APN-/- mice. These mice were fed with either vehicle or AdipoRon (50 mg/kg bodyweight per day) for 3 months. Cognitive functions of these mice were investigated. Neuropathological and molecular changes in the brains were examined. Results: Adiponectin deficiency in 5xFAD mice exacerbated memory deficits, and AD pathologies. Immunostaining demonstrated that microglia was reactivated but its phagocytic activity to Aβ was reduced in 5xFAD;APN-/- mice. Pro-inflammatory cytokine levels were elevated in the brain. Liquid chromatography–tandem mass spectrometry analysis confirmed that AdipoRon can cross the blood-brain barrier. AdipoRontreated 5xFAD and 5xFAD;APN-/- mice showed reduction of Aβ deposition in the cortex and hippocampus. AdipoRon also reduced generation of other cleavage products in amyloidosis. AdipoRon can suppress neuroinflammation, glial activation and resume the phagocytic activity of microglia. Mice treated with AdipoRon demonstrated increased activation of insulin signalling and insulin sensitisation. Lastly, AdipoRon reversed neuronal and dendritic spines reduction as well as cognitive functions in both 5xFAD and 5xFAD;APN-/- mice. Conclusion: In summary, our results demonstrated that APN deficiency exacerbated AD pathologies and neurodegeneration. Oral administration of AdipoRon can reverse cognitive impairments and AD pathologies by insulin sensitisation, demonstrating its therapeutic potential to treat AD.-
dc.languageeng-
dc.publisherHong Kong Academy of Medicine Press. The Journal's web site is located at http://www.hkmj.org/-
dc.relation.ispartofHong Kong Medical Journal-
dc.relation.ispartof24th Medical Research Conference-
dc.rightsHong Kong Medical Journal. Copyright © Hong Kong Academy of Medicine Press.-
dc.titleAdiponectin deficiency exacerbated neuropathologenesis and cognitive functions in Alzheimer’s disease mice: potential application of AdipoRon as Alzheimer’s disease treatment-
dc.typeConference_Paper-
dc.identifier.emailNg, CL: royclng@hku.hk-
dc.identifier.emailMa, KFO: oscarmkf@HKUCC-COM.hku.hk-
dc.identifier.emailChung, SK: skchung@hkucc.hku.hk-
dc.identifier.emailChan, KH: koonho@hku.hk-
dc.identifier.authorityNg, CL=rp02376-
dc.identifier.authorityChung, SK=rp00381-
dc.identifier.authorityChan, KH=rp00537-
dc.identifier.hkuros302696-
dc.identifier.volume25-
dc.identifier.issue1, Suppl. 1-
dc.identifier.spage35, abstract no. 52-
dc.identifier.epage35, abstract no. 52-
dc.publisher.placeHong Kong-

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