ePoster

TRIPLE ASSEMBLOIDS TO MODEL CORTICO-STRIATAL AND NIGRO-STRIATAL CONNECTIVITY IN PARKINSON’S DISEASE

Pauline Lachaland 8 co-authors

Paris Brain Institute

FENS Forum 2026 (2026)
Barcelona, Spain
Board PS03-08AM-371

Presentation

Date TBA

Board: PS03-08AM-371

Poster preview

TRIPLE ASSEMBLOIDS TO MODEL CORTICO-STRIATAL AND NIGRO-STRIATAL CONNECTIVITY IN PARKINSON’S DISEASE poster preview

Event Information

Poster Board

PS03-08AM-371

Abstract

Parkinson’s Disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra, resulting in motor deficits. These neurons project to the striatum, where they modulate cortical motor integration by medium spiny neurons (MSNs). Traditional animal models using neurotoxins or transgenic mutations offer insights into PD but fail to fully replicate the human disease, limiting treatment development.
To improve PD modelling, we developed a 3D human organoid system derived from induced pluripotent stem cells (iPSCs). This model integrates ventral midbrain organoids (VMO) representing DA neurons, ventral forebrain organoids (VFO) for striatal MSNs, and dorsal forebrain organoids (DFO) for cortical neurons, recreating key aspects of basal ganglia circuitry.
We confirmed DA neuron differentiation in VMOs, MSN markers (DARPP32) and GABA-expressing cells in VFOs, and glutamatergic cortical layers in DFOs by day 90. Enhanced maturation of DA neurons and cortical organization were observed, with DA and glutamatergic projections observed in VFO, in the vicinity of the MSNs.
Preliminary results using PRKN knock-out (KO) iPSCs, a gene linked to autosomal recessive PD, demonstrated altered calcium activity in VFO-VMO assembloids. These findings highlight the potential of this model to unravel mechanisms of DA neuron degeneration and basal ganglia circuit development in PD.

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