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The University of Southampton
Biological Sciences

Research project: Investigating the interface between metabolism and neurodegeneration

Currently Active: 
Yes
Project type: 
Grant

Efficient neuronal transmission requires steady energy production, supplied predominantly through glucose and lactate metabolism. This project will more closely examine this relationship between metabolism and synaptic communication during normal ageing and disease states.

 

Neurodegeneration is a key pathological hallmark of a number of disease states including: Alzheimer’s, Parkinson’s and Huntington’s disease. A number of these conditions also encompass alterations in neuronal metabolism as an early mitigating factor in disease progression. It is therefore of interest to investigate potential links between deranged neuronal energy production and impaired synaptic transmission.

 Efficient electro-chemical coupling between synapses requires constant yet flexible energy production. Under basal conditions, oxidation of glucose by neurons is near maximal, with activity-dependent (increased firing and synaptic activity) enhancement in utilisation correlating with increased glycolysis. While glycolysis is less efficient than oxidative metabolism (2 vs. 33 ATP per mol of glucose), it can generate sufficient ATP for neurons by producing it at a higher rate. Effective glucose metabolism has also previously been noted to be required for the induction of long term potentiation, a widely accepted cellular correlate of learning and memory. In addition to energy production, neuronal substrate metabolism also acts to replenish neurotransmitter levels, allowing increased synaptic activity. It is therefore of interest to investigate whether perturbations in energy/neurotransmitter production might underlie impaired synaptic functioning in neurodegenerative disease states.

 Brain slice electrophysiology and single cell amperometric oxygen flux detection will be used to investigate how pathophysiological features of Alzheimer’s disease alter metabolic flux and in turn impair synaptic connectivity. It is hoped that targets may in turn be highlighted and provide novel avenues for earlier treatment options.

Funding: Institute for Life Sciences
Funding duration: 06 October 2014 - 05 October 2017

Supervisors

 

Professor Peter Smith
Dr Mariana Vargas-Caballero

 

 

 

Related research groups

Biomedical Sciences
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