000281436 001__ 281436
000281436 005__ 20260105130637.0
000281436 0247_ $$2doi$$a10.1016/j.pbb.2025.174096
000281436 0247_ $$2pmid$$apmid:40939811
000281436 0247_ $$2ISSN$$a0091-3057
000281436 0247_ $$2ISSN$$a1873-5177
000281436 0247_ $$2altmetric$$aaltmetric:181541009
000281436 037__ $$aDZNE-2025-01121
000281436 041__ $$aEnglish
000281436 082__ $$a540
000281436 1001_ $$aCinar, Elif$$b0
000281436 245__ $$aAutophagy activation ameliorates cognitive deficits and alpha-synuclein pathology in an adeno-associated viral vector mediated rat model of Lewy body disorders.
000281436 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2025
000281436 3367_ $$2DRIVER$$aarticle
000281436 3367_ $$2DataCite$$aOutput Types/Journal article
000281436 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1762876849_13692
000281436 3367_ $$2BibTeX$$aARTICLE
000281436 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000281436 3367_ $$00$$2EndNote$$aJournal Article
000281436 520__ $$aLewy body disorders (LBD), including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB), are characterized by the aggregation of alpha-synuclein (a-syn). Despite shared pathological features, these disorders have distinct clinical characteristics, in terms of both motor and cognitive symptoms. We created a unique rat model of dual-site injection of adeno-associated viral vectors carrying human a-syn (AAV5-h-a-syn) simultaneously and bilaterally into the substantia nigra and dentate gyrus, to recapitulate both nigrostriatal and hippocampal-based a-syn pathology associated with PDD and DLB. Inspired by the distinct pathological features of the model, namely the CA2-dominated accumulation of phosphorylated a-syn, in the current study we aimed to evaluate comparatively the consequences of autophagic induction on a-syn pathology in these targeted areas. This was achieved by the chronic administration of rapamycin, for 8 weeks starting 10 weeks post-AAV injections. Behavioral assessments were conducted by evaluation of locomotor activity, anxiety-related behavior, object and spatial learning and memory. Histopathological examinations involved in-depth analysis of a-syn pathology, neuronal and synaptic integrity and autophagic markers. Results demonstrated that rapamycin significantly ameliorated cognitive deficits and reduced phosphorylated a-syn accumulation, significantly in CA2 throughout all its sublayers and partially in CA3 sublayers. Despite no alteration in NeuN and TH levels, synaptophysin expressions were decreased in both the hippocampus and striatum in a-syn overexpressing animals, which were partially restored by rapamycin treatment. Intriguingly, autophagic activation, as indicated by the increased expression of beclin-1, LC3-I/II, p62, and Atg proteins, was predominantly observed in the hippocampus but not in the striatum, suggesting region-specific differential response to autophagic induction in terms of a-syn pathology. This dual-site injection model provides a valuable tool for studying a-syn-related dementia and evaluating potential restorative therapies. Our findings underscore the importance of autophagy-targeting early interventions to alleviate cognitive deficits by reducing hippocampal a-syn burden in LBD.
000281436 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000281436 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000281436 650_7 $$2Other$$aAlpha-synucleinopathies
000281436 650_7 $$2Other$$aCA2
000281436 650_7 $$2Other$$aDementia
000281436 650_7 $$2Other$$aHippocampus
000281436 650_7 $$2Other$$aParkinson's disease
000281436 650_7 $$2Other$$aRapamycin
000281436 650_7 $$2Other$$aStratum pyramidale
000281436 650_7 $$2Other$$aSynaptic integrity
000281436 650_2 $$2MeSH$$aAnimals
000281436 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000281436 650_2 $$2MeSH$$aalpha-Synuclein: genetics
000281436 650_2 $$2MeSH$$aAutophagy: drug effects
000281436 650_2 $$2MeSH$$aAutophagy: physiology
000281436 650_2 $$2MeSH$$aRats
000281436 650_2 $$2MeSH$$aDependovirus: genetics
000281436 650_2 $$2MeSH$$aLewy Body Disease: pathology
000281436 650_2 $$2MeSH$$aLewy Body Disease: metabolism
000281436 650_2 $$2MeSH$$aLewy Body Disease: psychology
000281436 650_2 $$2MeSH$$aLewy Body Disease: therapy
000281436 650_2 $$2MeSH$$aMale
000281436 650_2 $$2MeSH$$aDisease Models, Animal
000281436 650_2 $$2MeSH$$aGenetic Vectors
000281436 650_2 $$2MeSH$$aCognitive Dysfunction: therapy
000281436 650_2 $$2MeSH$$aSirolimus: pharmacology
000281436 650_2 $$2MeSH$$aHumans
000281436 650_2 $$2MeSH$$aRats, Sprague-Dawley
000281436 7001_ $$aYalcin-Cakmakli, Gül$$b1
000281436 7001_ $$aAkyel, Hilal$$b2
000281436 7001_ $$0P:(DE-2719)2772760$$aUlusoy, Ayse$$b3$$udzne
000281436 7001_ $$aTel, Banu Cahide$$b4
000281436 7001_ $$aElibol, Bülent$$b5
000281436 773__ $$0PERI:(DE-600)2008734-2$$a10.1016/j.pbb.2025.174096$$gVol. 257, p. 174096 -$$p174096$$tPharmacology, biochemistry and behavior$$v257$$x0091-3057$$y2025
000281436 8564_ $$uhttps://pub.dzne.de/record/281436/files/DZNE-2025-01121%20SUP.zip
000281436 8564_ $$uhttps://pub.dzne.de/record/281436/files/DZNE-2025-01121_Restricted.pdf
000281436 8564_ $$uhttps://pub.dzne.de/record/281436/files/DZNE-2025-01121_Restricted.pdf?subformat=pdfa$$xpdfa
000281436 909CO $$ooai:pub.dzne.de:281436$$pVDB
000281436 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2772760$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE
000281436 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000281436 9141_ $$y2025
000281436 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2024-12-13$$wger
000281436 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bPHARMACOL BIOCHEM BE : 2022$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2024-12-13
000281436 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2024-12-13
000281436 9201_ $$0I:(DE-2719)1013044$$kAG Ulusoy$$lParkinson's and Spatial Omics$$x0
000281436 980__ $$ajournal
000281436 980__ $$aVDB
000281436 980__ $$aI:(DE-2719)1013044
000281436 980__ $$aUNRESTRICTED