Neuronal alterations in AKT isotype expression in schizophrenia.

Autor: Devine EA; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA. devineea@mail.uc.edu.; Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA. devineea@mail.uc.edu., Imami AS; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., Eby H; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., Sahay S; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., Hamoud AR; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., Golchin H; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., Ryan W; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., Shedroff EA; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., Arvay T; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., Joyce AW; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., Asah SM; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., Walss-Bass C; Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA., O'Donovan S; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., McCullumsmith RE; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.; Department of Psychiatry, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.; Neurosciences Institute, ProMedica, Toledo, OH, USA.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Oct 18. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1038/s41380-024-02770-8
Abstrakt: Schizophrenia is characterized by substantial alterations in brain function, and previous studies suggest insulin signaling pathways, particularly involving AKT, are implicated in the pathophysiology of the disorder. This study demonstrates elevated mRNA expression of AKT1-3 in neurons from schizophrenia subjects, contrary to unchanged or diminished total AKT protein expression reported in previous postmortem studies, suggesting a potential decoupling of transcript and protein levels. Sex-specific differential AKT activity was observed, indicating divergent roles in males and females with schizophrenia. Alongside AKT, upregulation of PDPK1, a critical component of the insulin signaling pathway, and several protein phosphatases known to regulate AKT were detected. Moreover, enhanced expression of the transcription factor FOXO1, a regulator of glucose metabolism, hints at possible compensatory mechanisms related to insulin signaling dysregulation. Findings were largely independent of antipsychotic medication use, suggesting inherent alterations in schizophrenia. These results highlight the significance of AKT and related signaling pathways in schizophrenia, proposing that these changes might represent a compensatory response to a primary defect of canonical insulin signaling pathways. This research underscores the need for a detailed understanding of these signaling pathways for the development of effective therapeutic strategies.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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