α-Synuclein induced toxicity in brain stem serotonin neurons mediated by an AAV vector driven by the tryptophan hydroxylase promoter
Wan, Oi Wan LU ; Shin, Eunju LU ; Mattsson, Bengt LU ; Caudal, Dorian ; Svenningsson, Per and Björklund, Anders LU
(2016)
In Scientific Reports
6.
- Abstract
We studied the impact of α-synuclein overexpression in brainstem serotonin neurons using a novel vector construct where the expression of human wildtype α-synuclein is driven by the tryptophan hydroxylase promoter, allowing expression of α-synuclein at elevated levels, and with high selectivity, in serotonergic neurons. α-Synuclein induced degenerative changes in axons and dendrites, displaying a distorted appearance, suggesting accumulation and aggregation of α-synuclein as a result of impaired axonal transport, accompanied by a 40% loss of terminals, as assessed in the hippocampus. Tissue levels of serotonin and its major metabolite 5-HIAA remained largely unaltered, and the performance of the α-synuclein overexpressing rats in tests... (More)
We studied the impact of α-synuclein overexpression in brainstem serotonin neurons using a novel vector construct where the expression of human wildtype α-synuclein is driven by the tryptophan hydroxylase promoter, allowing expression of α-synuclein at elevated levels, and with high selectivity, in serotonergic neurons. α-Synuclein induced degenerative changes in axons and dendrites, displaying a distorted appearance, suggesting accumulation and aggregation of α-synuclein as a result of impaired axonal transport, accompanied by a 40% loss of terminals, as assessed in the hippocampus. Tissue levels of serotonin and its major metabolite 5-HIAA remained largely unaltered, and the performance of the α-synuclein overexpressing rats in tests of spatial learning (water maze), anxiety related behavior (elevated plus maze) and depressive-like behavior (forced swim test) was not different from control, suggesting that the impact of the developing axonal pathology on serotonin neurotransmission was relatively mild. Overexpression of α-synuclein in the raphe nuclei, combined with overexpression in basal forebrain cholinergic neurons, resulted in more pronounced axonal pathology and significant impairment in the elevated plus maze. We conclude that α-synuclein pathology in serotonergic or cholinergic neurons alone is not sufficient to impair non-motor behaviors, but that it is their simultaneous involvement that determines severity of such symptoms.
(Less)
- author
- Wan, Oi Wan
LU
; Shin, Eunju
LU
; Mattsson, Bengt
LU
; Caudal, Dorian
; Svenningsson, Per
and Björklund, Anders
LU
- organization
- publishing date
- 2016-05-23
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Journal Article
- in
- Scientific Reports
- volume
- 6
- article number
- 26285
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:27211987
- scopus:84969915719
- wos:000376233700001
- ISSN
- 2045-2322
- DOI
- 10.1038/srep26285
- language
- English
- LU publication?
- yes
- id
- 3a558946-d1c0-4ca3-a544-6739eba9eba3
- date added to LUP
- 2016-11-23 14:03:50
- date last changed
- 2025-01-12 15:47:34
@article{3a558946-d1c0-4ca3-a544-6739eba9eba3,
abstract = {{<p>We studied the impact of α-synuclein overexpression in brainstem serotonin neurons using a novel vector construct where the expression of human wildtype α-synuclein is driven by the tryptophan hydroxylase promoter, allowing expression of α-synuclein at elevated levels, and with high selectivity, in serotonergic neurons. α-Synuclein induced degenerative changes in axons and dendrites, displaying a distorted appearance, suggesting accumulation and aggregation of α-synuclein as a result of impaired axonal transport, accompanied by a 40% loss of terminals, as assessed in the hippocampus. Tissue levels of serotonin and its major metabolite 5-HIAA remained largely unaltered, and the performance of the α-synuclein overexpressing rats in tests of spatial learning (water maze), anxiety related behavior (elevated plus maze) and depressive-like behavior (forced swim test) was not different from control, suggesting that the impact of the developing axonal pathology on serotonin neurotransmission was relatively mild. Overexpression of α-synuclein in the raphe nuclei, combined with overexpression in basal forebrain cholinergic neurons, resulted in more pronounced axonal pathology and significant impairment in the elevated plus maze. We conclude that α-synuclein pathology in serotonergic or cholinergic neurons alone is not sufficient to impair non-motor behaviors, but that it is their simultaneous involvement that determines severity of such symptoms.</p>}},
author = {{Wan, Oi Wan and Shin, Eunju and Mattsson, Bengt and Caudal, Dorian and Svenningsson, Per and Björklund, Anders}},
issn = {{2045-2322}},
keywords = {{Journal Article}},
language = {{eng}},
month = {{05}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{α-Synuclein induced toxicity in brain stem serotonin neurons mediated by an AAV vector driven by the tryptophan hydroxylase promoter}},
url = {{http://dx.doi.org/10.1038/srep26285}},
doi = {{10.1038/srep26285}},
volume = {{6}},
year = {{2016}},
}