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Sequential or Simul...
Sequential or Simultaneous Injection of Preformed Fibrils and AAV Overexpression of Alpha-Synuclein Are Equipotent in Producing Relevant Pathology and Behavioral Deficits
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- Negrini, Matilde (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Beteendevetenskapligt laboratorium,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Behavioural Neuroscience Laboratory,Lund University Research Groups
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- Tomasello, Giuseppe (författare)
- Lund University,Lunds universitet,Beteendevetenskapligt laboratorium,Forskargrupper vid Lunds universitet,Behavioural Neuroscience Laboratory,Lund University Research Groups
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- Davidsson, Marcus (författare)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Beteendevetenskapligt laboratorium,Molecular Neuromodulation,Lund University Research Groups,Behavioural Neuroscience Laboratory,Barrow Neurological Institute, Phoenix
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- Fenyi, Alexis (författare)
- The French National Centre for Scientific Research (CNRS)
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- Adant, Cécile (författare)
- Lund University
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- Hauser, Swantje (författare)
- Lund University,Lunds universitet,Beteendevetenskapligt laboratorium,Forskargrupper vid Lunds universitet,Behavioural Neuroscience Laboratory,Lund University Research Groups
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- Espa, Elena (författare)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Basal Ganglia Pathophysiology,Lund University Research Groups
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- Gubinelli, Francesco (författare)
- Lund University,Lunds universitet,Beteendevetenskapligt laboratorium,Forskargrupper vid Lunds universitet,Behavioural Neuroscience Laboratory,Lund University Research Groups
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- Manfredsson, Fredric P. (författare)
- Barrow Neurological Institute, Phoenix
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- Melki, Ronald (författare)
- The French National Centre for Scientific Research (CNRS)
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- Heuer, Andreas (författare)
- Lund University,Lunds universitet,Beteendevetenskapligt laboratorium,Forskargrupper vid Lunds universitet,Behavioural Neuroscience Laboratory,Lund University Research Groups
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(creator_code:org_t)
- 2022
- 2022
- Engelska 21 s.
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Ingår i: Journal of Parkinson's Disease. - 1877-7171. ; 12:4, s. 1133-1153
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Background: Preclinical rodent models for Parkinson's disease (PD) based on viral human alpha-synuclein (h-αSyn) overexpression recapitulate some of the pathological hallmarks as it presents in humans, such as progressive cell loss and additional synucleinopathy in cortical and subcortical structures. Recent studies have combined viral vector-based overexpression of human wild-type αSyn with the sequential or simultaneous inoculation of preformed fibrils (PFFs) derived from human αSyn. Objective: The goal of the study was to investigate whether sequential or combined delivery of the AAV vector and the PFFs are equipotent in inducing stable neurodegeneration and behavioral deficits. Methods: Here we compare between four experimental paradigms (PFFs only, AAV-h-αSyn only, AAV-h-αSyn with simultaneous PFFs, and AAV-h-αSyn with sequential PFFs) and their respective GFP control groups. Results: We observed reduction of TH expression and loss of neurons in the midbrain in all AAV (h-αSyn or GFP) injected groups, with or without additional PFFs inoculation. The overexpression of either h-αSyn or GFP alone induced motor deficits and dysfunctional dopamine release/reuptake in electrochemical recordings in the ipsilateral striatum. However, we observed a substantial formation of insoluble h-αSyn aggregates and inflammatory response only when h-αSyn and PFFs were combined. Moreover, the presence of h-αSyn induced higher axonal pathology compared to control groups. Conclusion: Simultaneous AAV and PFFs injections are equipotent in the presented experimental setup in inducing histopathological and behavioral changes. This model provides new and interesting possibilities for characterizing PD pathology in preclinical models and means to assess future therapeutic interventions.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- AAV
- alpha synuclein
- behavioral deficits
- dopamine
- inflammation
- motor deficits
- Parkinson's disease
- phosphorylated synuclein
- preclinical rodent model
- preformed fibrils
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Negrini, Matilde
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Tomasello, Giuse ...
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Davidsson, Marcu ...
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Fenyi, Alexis
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Adant, Cécile
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Hauser, Swantje
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visa fler...
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Espa, Elena
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Gubinelli, Franc ...
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Manfredsson, Fre ...
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Melki, Ronald
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Heuer, Andreas
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Journal of Parki ...
- Av lärosätet
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Lunds universitet