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Selective vulnerability of supragranular layer neurons in schizophrenia

Selective vulnerability of supragranular layer neurons in schizophrenia

Authors :
Batiuk, Mykhailo Y.
Tyler, Teadora
Mei, Shenglin
Rydbirk, Rasmus
Petukhov, Viktor
Sedmak, Dora
Frank, Erzsebet
Feher, Virginia
Habek, Nikola
Hu, Qiwen
Igolkina, Anna
Roszik, Lilla
Pfisterer, Ulrich
Petanjek, Zdravko
Adorjan, Istvan
Kharchenko, Peter V.
Khodosevich, Konstantin
Batiuk, Mykhailo Y.
Tyler, Teadora
Mei, Shenglin
Rydbirk, Rasmus
Petukhov, Viktor
Sedmak, Dora
Frank, Erzsebet
Feher, Virginia
Habek, Nikola
Hu, Qiwen
Igolkina, Anna
Roszik, Lilla
Pfisterer, Ulrich
Petanjek, Zdravko
Adorjan, Istvan
Kharchenko, Peter V.
Khodosevich, Konstantin
Source :
Batiuk , M Y , Tyler , T , Mei , S , Rydbirk , R , Petukhov , V , Sedmak , D , Frank , E , Feher , V , Habek , N , Hu , Q , Igolkina , A , Roszik , L , Pfisterer , U , Petanjek , Z , Adorjan , I , Kharchenko , P V & Khodosevich , K 2021 ' Selective vulnerability of supragranular layer neurons in schizophrenia ' .
Publication Year :
2021

Abstract

Schizophrenia is one of the most wide-spread mental brain disorders with complex and largely unknown etiology. To characterize the impact of schizophrenia at a cellular level, we performed single nucleus RNA sequencing of gt;190,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls (7 vs 11, respectively). In addition, to correlate data with cortical anatomy, gt;100,000 neurons were analyzed topographically by immunohistochemistry in an extended cohort of cases with schizophrenia and controls (10 vs 10). Compositional analysis of RNA sequencing data revealed reduction in relative abundance across all families of GABAergic neurons and a concomitant increase in principal neurons, which was most pronounced for supragranular subtypes (layers 2-3). Moreover, supragranular subtypes of GABAergic interneurons showed most dramatic transcriptomic changes. These results were substantiated by histological analysis, which revealed a reduction in the density of calretinin, calbindin and parvalbumin GABAergic interneurons particularly in layer 2. Common effect of schizophrenia on supragranular neuronal networks was underlined by downregulation of protein processing genes and upregulation of neuronal development/plasticity genes across supragranular subtypes of principal neurons and GABAergic interneurons. In situ hybridization and spatial transcriptomics further confirmed supragranular layer neuron vulnerability, revealing complexity of schizophrenia-affected cortical circuits. These point towards general network impairment within supragranular layers being a core substrate associated with schizophrenia symptomatology.Competing Interest StatementThe authors have declared no competing interest.

Details

Database :
OAIster
Journal :
Batiuk , M Y , Tyler , T , Mei , S , Rydbirk , R , Petukhov , V , Sedmak , D , Frank , E , Feher , V , Habek , N , Hu , Q , Igolkina , A , Roszik , L , Pfisterer , U , Petanjek , Z , Adorjan , I , Kharchenko , P V & Khodosevich , K 2021 ' Selective vulnerability of supragranular layer neurons in schizophrenia ' .
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1322777335
Document Type :
Electronic Resource