H2020Индивидуална стипендия2019–2021

SCAMPICITY · cAMP-dependend plasticity of striatal projection neurons in health and disease

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-04-01 → 2021-03-31
Финансиране от ЕС: 174 806 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Невронните връзки в стриатума на мозъка се изследват чрез влиянието на молекулата cAMP върху тяхната пластичност. Познаването на тези процеси при болестта на Паркинсон може да помогне за разработването на нови терапевтични подходи за контрол на движението.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

cAMP-dependend plasticity of striatal projection neurons in health and disease

Neurons are very complex cells, with complex functions. They build the foundation of how our brains work, and understanding neurons is therefore a necessary step to understand the brain. In this project we focused on a very specific type of neuron, the spiny projection neuron of the striatum. The striatum is an evolutionary conserved area of the brain and part of the basal ganglia, a sub-cortical network that is involved in the control of movement. Many movement disorders, such as Parkinson’s disease, are characterized by dysfunction of the basal ganglia and striatal neurons. Parkinson’s disease is the second most common neurodegenerative disorder and an increasing risk for aging societies. Unfortunately, there is no cure of the disease, and symptomatic treatment (such as with L-DOPA) is not without problems. Since striatal neurons play a major part in the disease pathology, advancing the knowledge about their function harbors the potential of developing new therapeutic approaches. In specific, this project was aimed at understanding the role of cyclic nucleotides in spiny projection neuron function. Cyclic nucleotides are important second messengers in many nerve cells, and their most prominent members are cyclic adenosine monophosphate and cyclic guanosine monophosphate (cAMP and cGMP, respectively). The first main objective therefore was to investigate how synaptic plasticity of striatal neurons is influenced by cyclic nucleotides, specifically cAMP. Secondly, we wanted to know if this regulation is altered in a model of Parkinson’s disease.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The project aims to reveal the so far unknown role of cAMP in structural and synaptic plasticity of striatal spiny projection neurons (SPNs) in health and disease. Striatal SPNs divide into two subgroups: the dSPNs and iSPNs. While dSPNs preferentially express the D1 dopamine (DA) receptor, iSPNs express the D2 receptor. Both are coupled to the cAMP second messenger cascade, however the D1-receptor activates and the D2-receptor inhibits it. DA has therefore opposite effects on the two SPN groups, both mediated by cAMP. Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterized by typical motor symptoms caused by the death of DA neurons and the subsequent lack of DA in the striatum. A long-standing but untested notion in the field is that loss of DA leads to aberrant cAMP levels and signaling in SPNs.The project will look at the role of cAMP in SPN synaptic and structural plasticity. We will use novel optogenetic tools that allow cell-type specific activation of cAMP, with high spatiotemporal resolution. Focusing on corticostriatal synaptic transmission, we want to ask if transient activation of cAMP alone is sufficient to induce plasticity (e.g. strengthening or weakening) of this synapse. Secondly, we will use known plasticity protocols and test if precise activation of cAMP can interrupted or potentiated them. Unpublished data suggest that in vivo drug treatments that presumably elevate cAMP in SPNs induce structural plasticity, i.e. loss of dendritic spines. Following this we will unravel if cell-type specific activation of cAMP is sufficient to induce structural changes and how this relates to synaptic plasticity. Lastly, we will test the long-standing notion that cAMP levels and the responsiveness of the cascade are altered in an animal model of PD. This project will advance our understanding of how SPNs work by unraveling cAMP’s role in plasticity, and potentially inform future strategies to combat PD.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF · HamburgКоординаторГермания