GliaSound

GENERATOR FUND

Awarded: 2021

GW4 community leads
University of Bath: Philip Regan (PI)
University of Bristol: Daniel Whitcomb
University of Exeter: Jonathon Witton

Project overview

Investigating the potential of ultrasound stimulation as a regulator of neuroimmune function.

Background

Our society is aging, and with it, an increasing prevalence of age-related health implications is adversely affecting population wellbeing. The brain is, arguably, the most affected and least treatable biological target of aging. As we age, cumulative risk factors contribute to the deterioration of brain health that can manifest in progressive cognitive impairment and increasingly, severe neurodegenerative diseases.

Neuroimmune signalling describes the complex interplay between cells in the brain that ordinarily serves to maintain brain health but, during aging and risk factor exposure, can become compromised to accelerate brain decline and disease progression. Data from recent studies hold promise that neuroimmune signalling may be modifiable by non-invasive brain stimulation techniques, such as ultrasound stimulation, which is emerging as a possible solution to combat neurodegeneration. The clinical success of ultrasound stimulation will ultimately be governed by knowing how, when and where in the brain to stimulate in order to effectively modulate neural function. Our regional research collaboration will enable unprecedented characterisation of ultrasound effects on neuroimmune signalling, ranging from the single-cell level to brain network analysis.

It is the vision of our GW4 community, together with current and future academic and industrial collaborators, to ultimately create meaningful impact through rational design of innovative cutting-edge ultrasonic brain therapeutics aimed at promoting healthy aging in our society.

Project summary

We propose to examine, and characterise, the modulation of microglia (the resident immune cells of the central nervous system) and neuroimmune function by ultrasound stimulation (US). Doing so will enable us to address whether, and how, US can activate protective neuroimmune responses and can therefore have clinical utility as a brain therapeutic.

Our initial project aims will be met across several experimental models, achieved through the collaborative expertise of our GW4 members. Experimental aims will incorporate (i) primary cultured microglia and neurons, to assess cell-specific effects and biological mechanisms of US neuroimmune modulation, (ii) live brain slices from transgenic mice to measure how US affects neuroimmune interactions in the working brain, and (iii) cultured brain slices, to assess dynamics of US modulation of neuronal physiology, and it’s dependence on neuroimmune signalling.

We anticipate that our proposed research will provide a platform on which to build and extend our GW4 community for long-term sustainable research into this important and innovative field.

Community site (GW4 Portal)