Naslov
Upper cortical layer-driven network impairment in schizophrenia

Autori
Batiuk, Mykhailo Y ; Tyler, Teadora ; Dragicevic, Katarina ; Mei, Shenglin ; Rydbirk, Rasmus ; Petukhov, Viktor ; Deviatiiarov, Ruslan ; Sedmak, Dora ; Frank, Erzsebet ; Feher, Virginia ; Habek, Nikola ; Hu, Qiwen ; Igolkina, Anna ; Roszik, Lilla ; Pfisterer, Ulrich ; Garcia- Gonzalez, Diego ; Petanjek, Zdravko ; Adorjan, Istvan ; Kharchenko, Peter V ; Khodosevich, Konstantin

Izvornik
Science advances (2375-2548) 8 (2022), 41; Eabn8367, 23

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
cerebral cortex, interneurons, mental disorders

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA