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HT4PD SIGNED
The role of the serotonin 5-HT4 receptor in motor and non-motor symptoms of Parkinson’s disease
Total Cost €
0EC-Contrib. €
0Partnership
0Views
0HT4PD project word cloud
Explore the words cloud of the HT4PD project. It provides you a very rough idea of what is the project "HT4PD" about.
severity
unilaterally
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projection
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action
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inhibitors
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serotonergic
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lid
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involuntary
occurring
transgenic
probe
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dorsolateral
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virally
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depotentiation
movements
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mechanism
spiny
knockdown
striatal
markers
altered
behaviors
attenuate
neuron
ltd
modulate
implicated
counteract
ssris
parkinson
protein
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mice
anxiety
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hippocampus
altering
contrast
diminished
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dopa
uncontrollably
investigation
ventral
pharmacologically
treatment
models
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ispns
dyskinesia
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behavior
striatum
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antidepressant
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ohda
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shows
depression
enriched
metabolism
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motor
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overexpression
cellular
examined
Project "HT4PD" data sheet
The following table provides information about the project.
| Coordinator |
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Organization address contact info |
| Coordinator Country | France [FR] |
| Total cost | 295˙061 € |
| EC max contribution | 295˙061 € (100%) |
| Programme |
1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility) |
| Code Call | H2020-MSCA-IF-2019 |
| Funding Scheme | MSCA-IF-EF-CAR |
| Starting year | 2021 |
| Duration (year-month-day) | from 2021-01-01 to 2023-12-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE | FR (PARIS) | coordinator | 295˙061.00 |
Map
Project objective
Parkinson’s Disease (PD) is caused by dopaminergic neuron loss resulting in motor symptoms that are treated with L-DOPA. However, ≤90% of patients develop involuntary movements, termed L-DOPA induced dyskinesia (LID). Another less well studied, but highly occurring PD symptom is depression. There is evidence that the serotonin system is implicated in both, LID and PD-linked depression. Serotonergic (5-HT) neurons uncontrollably release L-DOPA-derived dopamine, and HTR1a/b agonists counteract such release and LIDs. Serotonin re-uptake inhibitors (SSRIs) also attenuate LID, through a still unknown mechanism. The striatally enriched Gαs-coupled receptor, HTR4, has the potential to enhance excitability of spiny projection neurons, to affect the balance of striatal pathways that is disrupted in PD and is a candidate to modulate LID and PD-depression. D2 agonists reduce depressive behavior in PD models, pointing towards a role for the striatum. Specifically, the dorsolateral striatum shows diminished metabolism, in contrast to non-PD-depression where the ventral striatum is a substrate. HTR4 in cortex and hippocampus was linked to antidepressant action. Agonists and overexpression yield anti-depressant-like responses, however, striatal HTR4 in PD-depression has not been examined. 1. We will determine HTR4 protein expression on a cellular level (dSPNs, iSPNs) in transgenic mice. We will virally overexpress, knockdown and pharmacologically manipulate HTR4 and assess striatally-driven behaviors. 2. We will probe HTR4 in motor symptoms by altering expression/activity in unilaterally 6-OHDA lesioned mice. We will evaluate LID onset/severity, dyskinesia markers and LTP, depotentiation and LTD. 3. We will test bilaterally-lesioned mice with altered HTR4 expression/activity in depression/anxiety paradigms. We will determine the effect on the action of D2, HTR1a agonists and SSRIs. Our comprehensive investigation of HTR4 will lead to a new understanding and treatment of PD.
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