ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)

Biotechnologia Acta Т. 18, No. 2, 2025
P.  , Bibliography 5 , Engl.
UDC

HIPSC-DIFFERENTIATED DOPAMINERGIC NEURONS ARE A USEFUL TOOL FOR STUDYING THEIR NEUROPHYSIOLOGY AND MATURATION

.O. Pavlova ^1,2, L. Vandries ², V. Seutin

¹ Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv;
² Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liege, Belgium

Dopaminergic (DA) neurons play a crucial role in motor control, motivation, and cognition, with their degeneration in Parkinson’s disease leading to severe motor deficits. While rodent models are widely used, species-specific differences necessitate human-relevant models.

Aim. This study investigates the functional maturation of DA neurons derived from human induced pluripotent stem cells (IPS).

Methods. DA differentiation was performed using a mCherry-based TH reporter iPS line. Immunocytochemistry confirmed neuronal identity, while patch-clamp recordings assessed electrophysiological properties, including firing rate, action potential duration, Ih current, and dopamine sensitivity.

Results. TH expression was detected from day 10, reaching 64% by day 30. Electrophysiological maturation followed a distinct timeline, with spontaneous activity emerging around day 20 and stable pacemaking developing by day 40, along with D2 receptor-mediated autoinhibition.

Conclusions. Our findings demonstrate that hIPSC-derived DA neurons attain an adult-like profile by day 40, making them a viable model for studying Parkinson’s disease mechanisms and testing potential therapies. Further research will focus on slow pacemaking mechanisms in these neurons.

Keywords: Dopaminergic neurones, human induced pluripotent stem cells, electrophysiology, pacemaking, Parkinson's disease.

© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2025