| المصدر: |
Batiuk, M Y, Tyler, T, Dragicevic, K, Mei, S, Rydbirk, R, Petukhov, V, Deviatiiarov, R, Sedmak, D, Frank, E, Feher, V, Habek, N, Hu, Q, Igolkina, A, Roszik, L, Pfisterer, U, Garcia-Gonzalez, D, Petanjek, Z, Adorjan, I, Kharchenko, P V & Khodosevich, K 2022, ' Upper cortical layer-driven network impairment in schizophrenia ', Science Advances, vol. 8, no. 41, eabn8367 . https://doi.org/10.1126/sciadv.abn8367 |
| الوصف: |
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. |
