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In vivo quantificat...
In vivo quantification of glial activation in minipigs overexpressing human α-synuclein
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- Lillethorup, Thea Pinholt (författare)
- Aarhus University,Aarhus University Hospital
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- Glud, Andreas Nørgaard (författare)
- Aarhus University,Aarhus University Hospital
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- Landeck, Natalie (författare)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Alstrup, Aage Kristian Olsen (författare)
- Aarhus University,Aarhus University Hospital
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- Jakobsen, Steen (författare)
- Aarhus University Hospital,Aarhus University
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- Vang, Kim (författare)
- Aarhus University,Aarhus University Hospital
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- Doudet, Doris J. (författare)
- University of British Columbia,Aarhus University,Aarhus University Hospital
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- Brooks, David J. (författare)
- Imperial College London,Aarhus University,University of Newcastle upon Tyne,Aarhus University Hospital
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- Kirik, Deniz (författare)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Hinz, Rainer (författare)
- University of Manchester
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- Sørensen, Jens Christian (författare)
- Aarhus University
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- Landau, Anne M. (författare)
- Aarhus University,Aarhus University Hospital
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(creator_code:org_t)
- 2018-08-12
- 2018
- Engelska.
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Ingår i: Synapse. - : Wiley. - 0887-4476. ; 72:12
- Relaterad länk:
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http://dx.doi.org/10...
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https://www.research...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Parkinson’s disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha-synuclein (α-syn). The pathology of Parkinson’s disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergic response to overexpression of α-syn. We used positron emission tomography (PET) and the 18 kDa translocator protein radioligand, [11C](R)PK11195, to image brain microglial activation and (+)-α-[11C]dihydrotetrabenazine ([11C]DTBZ), to measure vesicular monoamine transporter 2 (VMAT2) availability in Göttingen minipigs following injection with recombinant adeno-associated virus (rAAV) vectors expressing either mutant A53T α-syn or green fluorescent protein (GFP) into the SN (4 rAAV-α-syn, 4 rAAV-GFP, 5 non-injected control minipigs). We performed motor symptom assessment and immunohistochemical examination of tyrosine hydroxylase (TH) and transgene expression. Expression of GFP and α-syn was observed at the SN injection site and in the striatum. We observed no motor symptoms or changes in striatal [11C]DTBZ binding potential in vivo or striatal or SN TH staining in vitro between the groups. The mean [11C](R)PK11195 total volume of distribution was significantly higher in the basal ganglia and cortical areas of the α-syn group than the control animals. We conclude that mutant α-syn expression in the SN resulted in microglial activation in multiple sub- and cortical regions, while it did not affect TH stains or VMAT2 availability. Our data suggest that microglial activation constitutes an early response to accumulation of α-syn in the absence of dopamine neuron degeneration.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- adeno-associated viral vectors
- alpha-synuclein
- animal model
- inflammation
- minipig
- Parkinson’s disease
- [C](R)PK11195
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Synapse
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Till lärosätets databas
- Av författaren/redakt...
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Lillethorup, The ...
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Glud, Andreas Nø ...
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Landeck, Natalie
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Alstrup, Aage Kr ...
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Jakobsen, Steen
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Vang, Kim
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visa fler...
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Doudet, Doris J.
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Brooks, David J.
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Kirik, Deniz
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Hinz, Rainer
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Sørensen, Jens C ...
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Landau, Anne M.
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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och Medicinska och f ...
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och Neurovetenskaper
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Synapse
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