Concussion, or mild traumatic brain injury (mTBI) affects millions world-wide each year due to motor accidents, falls, assaults, domestic violence, contact sports and war. It is now appreciated that a history of concussion increases the risk of developing long-term emotional and neurocognitive disorders. These include anxiety and depression, as well as neurodegenerative conditions such as Alzheimer’s. Critically, we do not know the mechanisms behind long-term negative effects of mTBI on brain health.
Over the last decade there is a growing literature emerging on how glial cells (microglia and astrocytes) and neuronal populations interact to control normal function and to understand how neuroinflammatory changes may be involved in the progression of a range of neuropsy chiatric and neurodegenerative disorders, a number of which are characterised by cognitive deficits.
In normal brain cognition is highly dependent on a balance between excitation (firing of pyramidal glutamatergic neurons) and inhibition (synchronisation of firing by parvalbumin containing GABAergic interneurons (PVI)). Gamma band oscillations, generated by these PVIs are crucial for maintenance of normal cognition. These interneurons are fast spiking, fast firing, have a high energy demand and as such are particularly susceptible to changes in neuroinflammation and oxidative stress. These interactions in different brains regions of relevance to cognition (e.g. prefrontal cortex & dorsal hippocampus) are now under intense scrutiny as changes in inflammation appear to be key drivers of brain injury, mood disorders and neurodegenerative disease. Understanding these interactions and their relationship over time in validated preclinical models related to TBI will aid in the identification and testing of novel therapeutic (both pharmacological and non-pharmacological (e.g. exercise)) interventions.
In the current project, we will investigate the immune cell response to mTBI in a clinically relevant mouse model. Our overall aims are to:
- Assess the influence mTBI on brain resident immune cells (microglia/astrocyte density and activation), brain tissue inflammation (multiplex cytokine array analysis) and neuronal populations (parvalbumin GABAergic interneurons and associated perineuronal nets)
- Utilise transgenic models and cell-depletion strategies in the mild TBI model. (Complimentary studies will be conducted in the moderate TBI model in Melbourne).
- Target immune and neuronal cell subtypes and functions in the brain to prevent / reverse neuronal and behavioural deficits in mice after mTBI.
Prof Michael Harte, Prof Stuart Allan, Dr Andrew Greenhalgh (The University of Manchester)
Dr Juliet Taylor, Prof Peter Crack (The University of Melbourne)
This project will be based at The University of Manchester, with at least 12 months spent at the University of Melbourne.
Candidates will need to meet the minimum entry requirements of both Universities to be accepted. You'll also need to be registered at both institutions for the duration of the programme. The entry criteria for the University of Melbourne can be found on their how to apply webpage. Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject to meet the entry criteria for the University of Manchester.
How to Apply
For further information about applying for one of the Manchester based projects can be found on our how to apply page. Candidates looking to apply for a Manchester-based project are encouraged to contact the named Manchester supervisor for an initial discussion before submitting an official application form. You MUST also submit an online application form - choose PhD Cancer Sciences.
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