RNA-sequencing suggests extracellular matrix and vasculature dysregulation could impair neurogenesis in schizophrenia cases with elevated inflammation.

Autor: North HF; Neuroscience Research Australia, Sydney, NSW, Australia.; Discipline of Psychiatry and Mental Health, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia., Weissleder C; Neuroscience Research Australia, Sydney, NSW, Australia.; Mechanism and therapy for genetic brain diseases, Institut Imagine, Paris, France., Bitar M; QIMR Berghofer, Herston, QLD, Australia., Barry G; OncoLife Therapeutics, Yeronga, QLD, Australia., Fullerton JM; Neuroscience Research Australia, Sydney, NSW, Australia.; School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia., Webster MJ; Laboratory of Brain Research, Stanley Medical Research Institute, 9800, Medical Center Drive, Rockville, MD, USA., Weickert CS; Neuroscience Research Australia, Sydney, NSW, Australia. weickerc@upstate.edu.; Discipline of Psychiatry and Mental Health, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. weickerc@upstate.edu.; Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY, USA. weickerc@upstate.edu.
Jazyk: angličtina
Zdroj: Schizophrenia (Heidelberg, Germany) [Schizophrenia (Heidelb)] 2024 May 04; Vol. 10 (1), pp. 50. Date of Electronic Publication: 2024 May 04.
DOI: 10.1038/s41537-024-00466-0
Abstrakt: A subgroup of schizophrenia cases with elevated inflammation have reduced neurogenesis markers and increased macrophage density in the human subependymal zone (SEZ; also termed subventricular zone or SVZ) neurogenic niche. Inflammation can impair neurogenesis; however, it is unclear which other pathways are associated with reduced neurogenesis. This research aimed to discover transcriptomic differences between inflammatory subgroups of schizophrenia in the SEZ. Total RNA sequencing was performed on SEZ tissue from schizophrenia cases, designated into low inflammation (n = 13) and high inflammation (n = 14) subgroups, based on cluster analysis of inflammation marker gene expression. 718 genes were differentially expressed in high compared to low inflammation schizophrenia (FDR p < 0.05) and were most significantly over-represented in the pathway 'Hepatic Fibrosis/Hepatic Stellate-Cell Activation'. Genes in this pathway relate to extracellular matrix stability (including ten collagens) and vascular remodelling suggesting increased angiogenesis. Collagen-IV, a key element of the basement membrane and fractones, had elevated gene expression. Immunohistochemistry revealed novel collagen-IV+ fractone bulbs within the human SEZ hypocellular gap. Considering the extracellular matrix's regulatory role in SEZ neurogenesis, fibrosis-related alterations in high inflammation schizophrenia may disrupt neurogenesis. Increased angiogenesis could facilitate immune cell transmigration, potentially explaining elevated macrophages in high inflammation schizophrenia. This discovery-driven analysis sheds light on how inflammation may contribute to schizophrenia neuropathology in the neurogenic niche.
(© 2024. The Author(s).)
Databáze: MEDLINE
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