Upregulated solute-carrier family genes in the hippocampus of schizophrenia can be rescued by antipsychotic medications.

Autor: Liu Z; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States of America. Electronic address: Zhengshan.Liu@UTSouthwestern.edu., Sun YH; Department of Biology, University of Rochester, Rochester, NY, United States of America., Ren Y; Department of Biology, University of Rochester, Rochester, NY, United States of America., Perez JM; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States of America., Scott D; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States of America., Tamminga C; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
Jazyk: angličtina
Zdroj: Schizophrenia research [Schizophr Res] 2024 Oct; Vol. 272, pp. 39-50. Date of Electronic Publication: 2024 Aug 24.
DOI: 10.1016/j.schres.2024.08.012
Abstrakt: Background and Hypothesis: Our previous studies have found that functional changes in the hippocampal circuit from dentate gyrus (DG) to cornu ammonis 3 and 1 (CA3, CA1) are highly associated with schizophrenia (SZ). However, no studies have explored the genetic expression across the three and two human hippocampal subfields (DG-CA3-CA1 and CA3-CA1) between subjects with SZ and healthy controls (CT).
Study Design: We matched cohorts between CT (n = 13) and SZ (n = 13). Among SZ, 6 subjects were on antipsychotics (AP) while 7 were off AP. We combined RNA-seq data from all three and two hippocampal subfields and performed differentially expressed gene analyses across DG-CA3-CA1 and CA3-CA1 affected by either SZ or AP.
Study Results: We found that differentially expressed genes (DEGs) from effects of SZ and AP across DG-CA3-CA1 and CA3-CA1 were highly associated with gene ontology terms related to hormonal and immune signaling, cellular mitosis and apoptosis, ion and amino acid transports, and protein modification and degradation. Additionally, we found that multiple genes related to solute-carrier family and immune signaling were significantly upregulated across DG-CA3-CA1 and CA3-CA1 in patients with SZ relative to CT, and AP consistently and robustly repressed the expression of these upregulated genes in the DG-CA3-CA1 and CA3-CA1 from subjects with SZ.
Conclusions: Together, these data suggest that the upregulated solute-carrier family genes in the hippocampus might have important roles in the pathophysiology of SZ, and that AP may reduce the symptoms of psychosis in SZ via rescuing the solute-carrier gene expression.
Competing Interests: Declaration of competing interest The authors declare no competing interests regarding this study and affirm that this manuscript has not been published before and it is currently not being considered for publication elsewhere. There has been no significant financial support for this work that could influence its outcome.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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