DOPAL and the Olfactory Bulb: a novel platform to mimic prodromal Parkinson's disease

A main limitation for the clinical use of cell transplantation in Parkinson’s disease (PD) is caused by the lack of reliable, inexpensive and easy models for the development, assessment and validation of these potentially powerful therapies. In this sense, organotypic brain slices can be a useful tool combining the main advantages of in vivo studies with the excellent experimental accessibility of in vitro models. Knowing that the olfactory bulb (OB) is one of the first part of the brain affected in PD, the aim of our study was to determine the utility of cultured olfactory bulb (OB) slices, as a platform to model prodromal PD. To induce Parkinson’s-like dysfunction, slices were treated with DOPAL, a metabolite of dopamine, physiologically present in the OB and whose concentration is increased in PD patients. DOPAL caused a significant increase the content of ROS and nitrites (p<0.05), resulting in reduced viability of treated slices. A possible mechanism of action is through the damage of mitochondria and the impairment of the physiological energy homeostasis in the cells. Using the Seahorse extracellular flux analysis, we detected signs of mitochondrial damage, such as significantly increased proton leak or significantly decreased coupling efficacy and spare respiratory capacity, all of which appeared within minutes DOPAL addition to culture media (p<0.05).

In conclusion, OB slices show great promise as a tool that could be used to test prospective cell-based therapies for PD.