Human midbrain organoids and PD


KEYWORDS

  • Astrocytes

  • Human samples

  • Parkinson's disease


TECHNIQUES

  • Brain organoids

  • iPSCs and reprogramming

  • Transcriptomics

Human-derived iPSCs and brain organoids to model Parkinson's disease in vitro

Our investigation is focused on understanding the role of astrocytes in the onset and development of Parkinson's disease (PD). The principal hallmark of PD is the selective neurodegeneration of dopaminergic neurons. Mounting evidence suggests that astrocytes may contribute to dopaminergic neurodegeneration through decreased homeostatic support and deficient neuroprotection. To clarify the exact role of astrocytes in the onset and development of PD, we use different human model from the induced pluripotent stem cells (iPSC)-derived astrocytes to the more complex midbrain organoids from PD patients. We found that PD astrocytes are characterized by a significant decrease in S100B and GFAP expression associated with marked decrease in astrocyte complexity. PD-derived astrocytes also demonstrate aberrant mitochondrial morphology, decreased mitochondrial activity and ATP production along with an increase of glycolysis and increased production of reactive oxygen species.

Human brain organoid obtained from donor-derived iPSCs, stained with astrocytic marker GFAP (AiryScan)


Publications related to this topic

  • Ramos-Gonzalez P, Mato S, Chara JC, Verkhratsky A, Matute C, Cavaliere F. Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation. NPJ Parkinsons Dis 2021; 7: 31. [LINK]

  • Cavaliere F, Cerf L, Dehay B, Ramos-Gonzalez P, De Giorgi F, Bourdenx M, Bessede A, Obeso JA, Matute C, Ichas F, Bezard E. In vitro α-synuclein neurotoxicity and spreading among neurons and astrocytes using Lewy body extracts from Parkinson disease brains. Neurobiol Dis 2017; 103: 101–112. [LINK]