Understanding the role of parvalbumin interneuron development in schizophrenia using human cerebral organoids

Información del proyecto

Schizophrenia Organoids

Identificador del acuerdo de subvención: 707109

DOI 10.3030/707109

Proyecto cerrado

Fecha de la firma de la CE 28 Abril 2016

Fecha de inicio 1 Septiembre 2017

Fecha de finalización 31 Agosto 2019

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total € 178 156,80

Aportación de la UE € 178 156,80

Coordinado por

INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH
Austria

Objetivo

Neuropsychiatric disorders account for 1/5 of the total disease burden in Europe causing mental anguish and decreased quality of life for those affected, especially for schizophrenia patients. An intriguing theory suggests that altered brain development results in schizophrenia, and the selective cellular defects in parvalbumin (PV) inhibitory interneurons observed in schizophrenic patient brains. However, the role of altered interneuron development in producing these pathophysiological hallmarks of schizophrenia is currently unknown due to a lack of cellular models of human interneuron development. Cerebral organoids are a revolutionary in vitro model of embryonic brain development generating complex brain circuits and recapitulating many aspects of interneuron development. The generation of organoid tissue from hiPSCs allows for the growth of patient-specific brain tissue. Therefore, the current proposal will develop a cerebral organoid schizophrenia model to analyze PV-interneuron development. First, cerebral organoids will be grown from patient-derived hiPSCs genetically modified to include a PV-GFP reporter. Using this reporter, genome-wide PV-specific gene expression will be analyzed to identify deregulated developmental pathways during PV-interneuron development. Second, a phenotypic analysis of PV-interneuron development will determine how PV-interneuron synaptic morphology and/or migration are altered in this cerebral organoid schizophrenia model. These assays are relevant to disease-related pathology, and will include axonal morphological analysis and a novel organoid co-culture migration assay. These results will determine the role of interneuron development in the pathophysiology of neuropsychiatric disease for the first time in human tissue. Understanding the developmental mechanisms of schizophrenia will address a major unmet therapeutic need by inspiring new avenues of innovative therapeutic strategies.

Ámbito científico

Not validated

• medical and health sciences › basic medicine › physiology › pathophysiology
• medical and health sciences › medical biotechnology › cells technologies › stem cells
• medical and health sciences › basic medicine › pathology
• medical and health sciences › clinical medicine › psychiatry › schizophrenia
• natural sciences › biological sciences › genetics › genomes

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility

Tema(s)

• MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF)

Convocatoria de propuestas

H2020-MSCA-IF-2015

Régimen de financiación

MSCA-IF-EF-ST - Standard EF

Coordinador

INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH

• Aportación neta de la UEn: € 178 156,80
• Dirección: DR BOHRGASSE 3 ; 1030 Wien ; Austria
• Región: Ostösterreich › Wien › Wien
• Tipo de actividad: Private for-profit entities (excluding Higher or Secondary Education Establishments)
• Coste total: € 178 156,80