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Neurotrophin-induced strengthening of synaptic connectivity: cellular mechanisms and functional effects on memory storage in the young adult and aged brain

Objective



Neurotrophins belong to a family of molecules, associated with nerve tissues, which have the capacity to affect a variety of cell growth parameters. Their importance in development of the nervous system is without question and well detailed but in the adult the significance of neurotrophins in the normal functioning of the central nervous system has been so far less clear.
Recently it has been shown in the in vitro hippocampal slice preparation that brain-derived neurotrophic factor, BDNF, can create a state of long-term potentiation (LTP) associated with heightened synaptic connectivity. The mechanism of BDNF-LTP is, analogous to long-term memory formation, dependent on protein synthesis. A further study from the coordinator of this proposal went on to show BDNF-LTP in intact young adult rats. These striking findings and others suggest clearly:
1, that BDNF can have significant influence in relation to memory 2, that interventional studies employing BDNF are exaggerations of a normal component of synaptic stabilization and memory storage in the intact adult.
The present proposal is designed to explore these two suggestions and, in line with the BIOTECHNOLOGY Area 4.4 Work Programme, to extend the investigation to aged animals.
A multidisciplinary consortium of European scientists all with international reputations, has been drawn together and a project based on three work packages has been created for:
1, Exploration of synaptic mechanisms and gene expression in BDNF-LTP. 2, Determination of the functional consequences of BDNF-LTP 3, Investigation of the involvement of BDNF-LTP in normal memory development
The aim is to run in parallel a programme of relatively basic research and functional studies designed to explore the possible role of BDNF interventions in promotion of memory. The immediacy of application of these latter studies to alleviation of memory impairment in senile dementia is noted. The exploitation plans will benefit a major European industrial concern.
The work proposed both fits the BIOTECHNOLOGY work programme and gains added value from being given a European dimension. The technologies involved cannot all be undertaken at any one of the involved research centres.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

UNIVERSITY OF BERGEN
Address
19,Aarstadveien 19
5009 Bergen
Norway

Participants (4)

Glaxo Research and Development Ltd
United Kingdom
Address
Gunnels Wood Road
SG1 2NY Stevenage
MEDICAL RESEARCH COUNCIL
United Kingdom
Address
The Ridgeway Mill Hill
NW7 1AA London
The Provost Fellows and Scholars of the Holy and Undivided Trinity of Queen Elizabeth near Dublin hereinafter TCD
Ireland
Address
East Theatre, Trinity College
2 Dublin
UNIVERSITY COLLEGE LONDON
United Kingdom
Address
Gower Street
London