Building human Midbrain-Striatum assembloids for in vitro modeling of Parkinson’s disease
Human brain organoids have a great potential for in vitro modelling of neurodegenerative diseases such as Parkinson’s disease (PD). Specifically, midbrain organoids have been a useful tool for studying the disease hallmarks, such as dopaminergic neuron’s degeneration and α-synuclein aggregation. However, the midbrain is not the only affected brain region in PD and to elucidate the initiation and progression of dopaminergic neuron’s degeneration we aim at studying their connectivity with their neighbouring brain region, the striatum. The nigrostriatal pathway, which is the connection between the midbrain and the dorsal striatum, is involved in the facilitation of the voluntary movement and is highly affected in PD. The dopamine that is released from the dopaminergic neurons binds to dopaminergic receptors on the GABAergic medium spiny neurons (MSNs) in the dorsal striatum and modulates the activity of basal ganglia through the direct and indirect pathway. In this study, we aim to establish a midbrain- striatum assembloid in vitro model that will recapitulate the physiological properties of the nigrostriatal pathway. Here we show the generation of striatum organoids that successfully develop striatum specific neurons as well as of midbrain- striatum assembloids recapitulating the nigrostriatal dopaminergic neurons projections.