Upper cortical layer-driven network impairment in schizophrenia.

Autor: Batiuk MY; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Tyler T; Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest H-1085, Hungary., Dragicevic K; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Mei S; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA., Rydbirk R; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Petukhov V; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Deviatiiarov R; The National Center for Personalized Medicine of Endocrine Diseases, Moscow 115478, Russia.; Kazan Federal University, Kazan 420043, Russia., Sedmak D; Croatian Institute for Brain Research and Center of Excellence for Basic, Clinical and Translational Neuroscience, School of Medicine, University of Zagreb, Zagreb 10000, Croatia., Frank E; Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest H-1085, Hungary., Feher V; Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest H-1085, Hungary., Habek N; Croatian Institute for Brain Research and Center of Excellence for Basic, Clinical and Translational Neuroscience, School of Medicine, University of Zagreb, Zagreb 10000, Croatia., Hu Q; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA., Igolkina A; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.; St. Petersburg Polytechnical University, St. Petersburg 195251, Russia., Roszik L; Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest H-1085, Hungary., Pfisterer U; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Garcia-Gonzalez D; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Petanjek Z; Croatian Institute for Brain Research and Center of Excellence for Basic, Clinical and Translational Neuroscience, School of Medicine, University of Zagreb, Zagreb 10000, Croatia., Adorjan I; Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest H-1085, Hungary., Kharchenko PV; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA., Khodosevich K; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2022 Oct 14; Vol. 8 (41), pp. eabn8367. Date of Electronic Publication: 2022 Oct 12.
DOI: 10.1126/sciadv.abn8367
Abstrakt: Schizophrenia is one of the most widespread and complex mental disorders. To characterize the impact of schizophrenia, we performed single-nucleus RNA sequencing (snRNA-seq) of >220,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls. In addition, >115,000 neurons were analyzed topographically by immunohistochemistry. Compositional analysis of snRNA-seq data revealed a reduction in abundance of GABAergic neurons and a concomitant increase in principal neurons, most pronounced for upper cortical layer subtypes, which was substantiated by histological analysis. Many neuronal subtypes showed extensive transcriptomic changes, the most marked in upper-layer GABAergic neurons, including down-regulation in energy metabolism and up-regulation in neurotransmission. Transcription factor network analysis demonstrated a developmental origin of transcriptomic changes. Last, Visium spatial transcriptomics further corroborated upper-layer neuron vulnerability in schizophrenia. Overall, our results point toward general network impairment within upper cortical layers as a core substrate associated with schizophrenia symptomatology.
Databáze: MEDLINE