Title : Continuous real-time monitoring of brain extracellular fluid using microamperometric sensors and their application in a humanized mouse model of Parkinson’s disease
In vivo amperometry is an electroanalytical technique whereby a sensitive and selective microelectrochemical sensor is implanted into a particular brain region for continuous real-time recordings of a particular neurochemical. A suitable potential is applied to the sensor surface, generating a faradaic current that is proportional to the concentration of the detected neurochemical. This presentation will discuss the in vitro development and characterization of an electrochemical sensor through to its subsequent in vivo characterization in the rodent brain and its eventual application in an animal model of disease. Current work is focusing on the ability of this technique to measure neurochemical transitions in a humanized mouse model of Parkinson’s disease (PD). In summary, PD patient-derived induced pluripotent stem cells (iPSC) are differentiated into dopaminergic neurons and transplanted into the striatum of NOD SCID mice to facilitate anatomical integration over a couple of months. To date, there has been limited translation from existing animal models of PD to clinical neuroprotection in human populations. A large number of potentially neuroprotective compounds from a broad range of pharmacological groups have been identified in rodent and primate models, however, none have proven neuroprotective during clinical testing. The general consensus is that this disparity is mainly due to the aetiopathogenic diversity of PD and humanised models can potentially bridge the gap between standard pre-clinical animal models of PD and clinical translation. This humanised mouse model will facilitate unprecedented access to perform amperometric recordings within the microenvironment of transplanted PD human cells.
Audience take away:
• How to develop and characterize a sensitive and selective amperometric sensor in vivo.
• How to characterize an amperometric sensor in rodent brain extracellular fluid.
• The application of amperometry to measure from within transplanted PD human cells.
• Knowledge of work being performed by SysMedPD consortium on the development of a neuroprotective treatment to slow down the progression of PD.