In brain disorders where there is disrupted neural signalling, replacing missing neurochemicals via oral therapy may fail to restore the natural temporal sequencing required for normal function. For Parkinson's disease (PD), the effectiveness of oral therapy used to replace dopamine is usually limited to a handful of years before the appearance of side effects.
We believe that optimising treatment for PD requires restoration of natural patterns of dopamine activity, involving phasic pulses of dopamine agonists of several seconds in duration, upon low tonic background levels. We have therefore designed technology to emulate the natural timing of dopamine release in order to reinforce only useful actions, with the aim of avoiding the development of unwanted movements (dyskinesias) and other side effects of oral therapy.
We have developed a liposome-based system to deliver receptor agonists at optimal timing to specific areas in the brain. Coupled with a controller system utilising focussed ultrasound to target brain areas non-invasively, we have applied various approaches to measure agonist release and evaluate cellular effects in target areas.
In this talk I will overview our proof-of-concept work delivering dopamine agonists, demonstrating neuromodulation effects of phasic receptor activation in neurons recorded in vitro and in vivo in rats. I will also show behavioural data using our sheep neurotoxin model, designed to facilitate scale-up to a brain with similar architecture to humans. Because of the targeted non-invasive nature of the technology, the system can also be used to deliver other neurochemicals requiring a programmed temporal regimen. To exemplify this, I will also show preliminary application of the technology to dampen epileptiform activity in the brain designed for on-demand focal seizure suppression.
N.B. References available upon request.
Zoom link for Professor John Reynolds' seminar
Zoom password: bioc
|Date||Tuesday, 6 September 2022|
|Time||12:00pm - 1:00pm|
|Audience||Undergraduate students,Postgraduate students,Staff|
|Event Category||Health Sciences|
Online and in-person
|Location||Biochemistry Seminar Room G.13 (BIG13) and via Zoom, Dunedin|
|Contact Name||Department of Biochemistry|