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Enhanced functional recovery by levodopa is associated with decreased levels of synaptogyrin following stroke in aged mice

Häggman Henrikson, Jens ; Pombo Antunes, Ana Rita LU ; Wieloch, Tadeusz LU and Ruscher, Karsten LU (2020) In Brain Research Bulletin 155. p.61-66
Abstract

Levodopa is a precursor to dopamine that has been shown to improve functional recovery following stroke partly achieved through mechanisms of brain plasticity. This study investigates if dopamine might affect plasticity by having a direct effect on synaptic plasticity through alterations in neurotransmitter release and re-uptake. Synaptogyrin is a synaptic vesicle protein that has been suggested to be involved in dopamine re-uptake in the synaptic terminal. Therefore, we investigated if levodopa has an effect on the expression of synaptogyrin 1. Thy1-YFP mice were subjected to photothrombosis as an experimental model of stroke. Starting two days after surgery they were treated with either levodopa or a vehicle solution (saline) on a... (More)

Levodopa is a precursor to dopamine that has been shown to improve functional recovery following stroke partly achieved through mechanisms of brain plasticity. This study investigates if dopamine might affect plasticity by having a direct effect on synaptic plasticity through alterations in neurotransmitter release and re-uptake. Synaptogyrin is a synaptic vesicle protein that has been suggested to be involved in dopamine re-uptake in the synaptic terminal. Therefore, we investigated if levodopa has an effect on the expression of synaptogyrin 1. Thy1-YFP mice were subjected to photothrombosis as an experimental model of stroke. Starting two days after surgery they were treated with either levodopa or a vehicle solution (saline) on a daily basis until day seven following surgery. On day seven they were sacrificed and their brains stained for Dopamine 1 receptor (D1R), Dopamine 2 receptor (D2R) and Parvalbumin (PV). Neu-N stainings were used to estimate infarct size. A second group of mice were subjected to photothrombosis and also treated with either levodopa or a vehicle solution in the same manner as previously mentioned. On day seven they were then sacrificed, and samples of brain tissue were taken for protein determination. Western blots were carried out to investigate possible differences in synaptogyrin expression between the two groups. Immunofluorescent stains showed the presence of dopamine receptors on the YFP-positive neurons and on PV-expressing neurones. Our Western Blot analysis showed a significant decrease in the expression of synaptogyrin in levodopa-treated mice. Our stains showed co-localisation with Thy-1 neurones and PV-expressing neurones for both D1 and D2 receptors. This indicates that dopamine has the ability to bind to, and directly influence cortical neurons, as well as inhibitory interneurons. We discovered a considerable decrease in synaptogyrin expression through levodopa treatment, suggesting that this might be a mechanism for regulating brain plasticity.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aged animals, Dopamine signalling, Neuronal plasticity, Stroke recovery, Synaptogyrin
in
Brain Research Bulletin
volume
155
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:85076113887
ISSN
0361-9230
DOI
10.1016/j.brainresbull.2019.11.019
language
English
LU publication?
yes
id
b6ea1ef7-07dd-4f9d-ac74-e43ed1c7f7a9
date added to LUP
2019-12-19 10:31:17
date last changed
2020-01-13 02:36:56
@article{b6ea1ef7-07dd-4f9d-ac74-e43ed1c7f7a9,
  abstract     = {<p>Levodopa is a precursor to dopamine that has been shown to improve functional recovery following stroke partly achieved through mechanisms of brain plasticity. This study investigates if dopamine might affect plasticity by having a direct effect on synaptic plasticity through alterations in neurotransmitter release and re-uptake. Synaptogyrin is a synaptic vesicle protein that has been suggested to be involved in dopamine re-uptake in the synaptic terminal. Therefore, we investigated if levodopa has an effect on the expression of synaptogyrin 1. Thy1-YFP mice were subjected to photothrombosis as an experimental model of stroke. Starting two days after surgery they were treated with either levodopa or a vehicle solution (saline) on a daily basis until day seven following surgery. On day seven they were sacrificed and their brains stained for Dopamine 1 receptor (D1R), Dopamine 2 receptor (D2R) and Parvalbumin (PV). Neu-N stainings were used to estimate infarct size. A second group of mice were subjected to photothrombosis and also treated with either levodopa or a vehicle solution in the same manner as previously mentioned. On day seven they were then sacrificed, and samples of brain tissue were taken for protein determination. Western blots were carried out to investigate possible differences in synaptogyrin expression between the two groups. Immunofluorescent stains showed the presence of dopamine receptors on the YFP-positive neurons and on PV-expressing neurones. Our Western Blot analysis showed a significant decrease in the expression of synaptogyrin in levodopa-treated mice. Our stains showed co-localisation with Thy-1 neurones and PV-expressing neurones for both D1 and D2 receptors. This indicates that dopamine has the ability to bind to, and directly influence cortical neurons, as well as inhibitory interneurons. We discovered a considerable decrease in synaptogyrin expression through levodopa treatment, suggesting that this might be a mechanism for regulating brain plasticity.</p>},
  author       = {Häggman Henrikson, Jens and Pombo Antunes, Ana Rita and Wieloch, Tadeusz and Ruscher, Karsten},
  issn         = {0361-9230},
  language     = {eng},
  pages        = {61--66},
  publisher    = {Elsevier},
  series       = {Brain Research Bulletin},
  title        = {Enhanced functional recovery by levodopa is associated with decreased levels of synaptogyrin following stroke in aged mice},
  url          = {http://dx.doi.org/10.1016/j.brainresbull.2019.11.019},
  doi          = {10.1016/j.brainresbull.2019.11.019},
  volume       = {155},
  year         = {2020},
}