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SELF-FUNDING MSc BY RESEARCH: Modulation of Brain Energy Metabolism by Astrocytic G-protein-coupled Receptors


   School of Physiology and Pharmacology

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  Dr A Teschemacher  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

It has been becoming increasingly clear that ‘neuro’science research must consider the roles of non-neuronal cells in the central nervous system if integrated brain function is to be understood. We have by now come to appreciate that astrocytes, the most abundant type of glia cells in the brain, play fundamental roles in neurotransmission, not only by fuelling the underlying cellular processes and by removing waste products, but also by integrating, amplifying, and modulating neuronal signals (Verkhratsky et al., 2015). Astrocytes handle glucose intake across the blood-brain barrier, contain the glycogen stores of the brain and, following glycolysis, release lactate into the extracellular space. This lactate may support neuronal function in states of increased energy demand, for example during memory formation (Alberini et al., 2017). However, beyond energy supply, recent evidence has suggested that lactate also acts as extracellular signalling molecule, for example in context of central arousal to salient stimuli, or in autonomic control (Tang et al., 2014;Teschemacher et al., 2015;Mosienko et al., 2015;Mosienko et al., 2018).

 Whilst lacking in electrical excitability, astrocytes express a plethora of G-protein-coupled receptors and highly complex intracellular signalling cascades of which we currently have only limited understanding. Over the recent decade, molecular and imaging tools suitable for investigating these have been developed. This research project will use astrocytes in dissociated and slice cultures, viral vector transgenesis, confocal imaging and biosensor electrode measurements to study the effects of GPCR activation on lactate production and release.

 


Funding Notes

This project is for students who can fund the project themselves; there is no financial support.
Please apply to the Faculty of Life Sciences, School of Physiology and Pharmacology, selecting the programme 'MSc by Research'
http://www.bristol.ac.uk/study/postgraduate/apply/

References

1. Alberini CM, Cruz E, Descalzi G, Bessieres B, Gao V (2017) Astrocyte glycogen and lactate: New insights into learning and memory mechanisms. GLIA 66:1244-1262.
2. Mosienko V, Rasooli-Nejad S, Kishi K, De Both M, Jane D, Huentelman MJ, Kasparov S, Teschemacher AG (2018) Putative receptors underpinning L-lactate signalling in locus coeruleus. Neuroglia 1:365-doi:10.3390/neuroglia1020025.
3. Mosienko V, Teschemacher AG, Kasparov S (2015) Is L-lactate a novel signaling molecule in the brain? J Cereb Blood Flow Metab 35:1069-1075.
4. Tang F, Lane S, Korsak A, Paton JF, Gourine AV, Kasparov S, Teschemacher AG (2014) Lactate-mediated glia-neuronal signaling in the mammalian brain. Nature Communications 5:3284-DOI: 10.1038/ncomms4284.
5. Teschemacher AG, Gourine AV, Kasparov S (2015) A Role for Astrocytes in Sensing the Brain Microenvironment and Neuro-Metabolic Integration. Neurochem Res 40:2386-2393.
6. Verkhratsky A, Nedergaard M, Hertz L (2015) Why are astrocytes important? Neurochem Res 40:389-401.

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