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Visualization of early oligomeric α‐synuclein pathology and its impact on the dopaminergic system in the (Thy‐1)‐h[A30P]α‐syn transgenic mouse model
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- Behere, Anish, 1993- (författare)
- Uppsala universitet,Institutionen för folkhälso- och vårdvetenskap,Molecular Geriatrics,Department of Public Health and Caring Sciences Uppsala University Uppsala Sweden
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- Thörnqvist, Per-Ove (författare)
- Uppsala universitet,Winberg: Beteendeneuroendokrinologi,Department of Neuroscience, Physiology Unit Uppsala University Uppsala Sweden
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- Winberg, Svante (författare)
- Uppsala universitet,Winberg: Beteendeneuroendokrinologi,Department of Neuroscience, Physiology Unit Uppsala University Uppsala Sweden
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- Ingelsson, Martin (författare)
- Uppsala universitet,Geriatrik,Department of Public Health and Caring Sciences Uppsala University Uppsala Sweden
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- Bergström, Joakim (författare)
- Uppsala universitet,Geriatrik,Department of Public Health and Caring Sciences Uppsala University Uppsala Sweden
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- Ekmark-Lewén, Sara (författare)
- Uppsala universitet,Geriatrik,Department of Public Health and Caring Sciences Uppsala University Uppsala Sweden
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(creator_code:org_t)
- 2021-07-22
- 2021
- Engelska.
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Ingår i: Journal of Neuroscience Research. - : John Wiley & Sons. - 0360-4012 .- 1097-4547. ; 99:10, s. 2525-2539
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Abstract
Ämnesord
Stäng
- Aggregation of alpha-synuclein (alpha-syn) into Lewy bodies and Lewy neurites is a pathological hallmark in the Parkinson ' s disease (PD) brain. The formation of alpha-syn oligomers is believed to be an early pathogenic event and the A30P mutation in the gene encoding alpha-syn, causing familial PD, has been shown to cause an accelerated oligomerization. Due to the problem of preserving antigen conformation on tissue surfaces, alpha-syn oligomers are difficult to detect ex vivo using conventional immunohistochemistry with oligomer-selective antibodies. Herein, we have instead employed the previously reported alpha-syn oligomer proximity ligation assay (ASO-PLA), along with a wide variety of biochemical assays, to discern the pathological progression of alpha-syn oligomers and their impact on the dopaminergic system in male and female (Thy-1)-h[A30P]alpha-syn transgenic (A30P-tg) mice. Our results reveal a previously undetected abundance of alpha-syn oligomers in midbrain of young mice, whereas phosphorylated (pS129) and proteinase k-resistant alpha-syn species were observed to a larger extent in aged mice. Although we did not detect loss of dopaminergic neurons in A30P-tg mice, a dysregulation in the monoaminergic system was recorded in older mice. Taken together, ASO-PLA should be a useful method for the detection of early changes in alpha-syn aggregation on brain tissue, from experimental mouse models in addition to post mortem PD cases.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- A30PA30P. alpha-synuclein
- oligomers
- Parkinson's disease
- proximity ligation assay
- pS129
- Medical Science
- Medicinsk vetenskap
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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