Role of cholesterol in neurotransmitter receptor trafficking and synaptic plasticity

Projektinformationen

SynaptoChol

ID Finanzhilfevereinbarung: 299864

Abgeschlossenes Projekt

Startdatum 1 August 2012

Enddatum 20 November 2014

Finanziert unter

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Gesamtkosten € 168 896,40

EU-Beitrag € 168 896,40

Koordiniert durch

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain

Ziel

Synaptic connections in the brain are continuously remodeled in response to neuronal activity. This process, known as synaptic plasticity, is widely thought to underlie learning and memory, and to be altered in several cognitive disorders. An important aspect of synaptic plasticity is the regulated movement of neurotransmitter receptors in and out of the synaptic membrane.
Cholesterol is an essential membrane component, and it plays a major role in membrane compartmentalization and trafficking. Although cholesterol only accounts for 2% of the body’s weight, the brain contains 25% of the body’s total cholesterol. The enrichment in cholesterol suggests a relevant role for this lipid in brain function. In fact, it, it is being increasingly recognized that cholesterol homeostasis have a role in neurological diseases. However, the precise role of lipids in neurotransmitter receptor trafficking is virtually unexplored. Here, we hypothesize that cholesterol plays a direct role in neurotransmitter receptor trafficking and therefore contributes to synaptic plasticity.
To test this hypothesis, we are developing genetic tools to manipulate cholesterol levels in living neurons. We take advantage of the fact that neurons possess a unique strategy to metabolize the cholesterol originally provided by astrocytes, through the expression of the enzyme CYP46A1. To alter cholesterol content in a cell autonomous way, we will manipulate the levels of CYP46A1 exclusively in neurons. To evaluate the physiological consequences, electrophysiological recordings and cell biological studies will be performed in organotypic hippocampal slice cultures. Hence, this proposal involves the use of a multidisciplinary approach.
We believe that this project will contribute to define the influence of cholesterol in synaptic plasticity. In addition to its intrinsic value, the knowledge generated should help to understand the cognitive deficits typical of disorders due cholesterol homeostasis genes.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › biochemistry › biomolecules › lipids
• medical and health sciences › basic medicine › physiology › homeostasis
• natural sciences › biological sciences › biochemistry › biomolecules › proteins › enzymes

Programm/Programme

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Thema/Themen

• FP7-PEOPLE-2011-IEF - Marie-Curie Action: "Intra-European fellowships for career development"

Aufforderung zur Vorschlagseinreichung

FP7-PEOPLE-2011-IEF
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

MC-IEF - Intra-European Fellowships (IEF)

Koordinator

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS

Kontakt Verwaltung

Alberto Sereno Alvarez (Mr.)

• EU-Beitrag: € 168 896,40
• Adresse: CALLE SERRANO 117 ; 28006 Madrid ; Spanien
• Region: Comunidad de Madrid › Comunidad de Madrid › Madrid
• Aktivitätstyp: Research Organisations
• Gesamtkosten: Keine Daten