Metabolic Insights into Neuropsychiatric Illnesses and Ketogenic Therapies: A Transcriptomic View DOI Open Access
Smita Sahay, Priyanka Pulvender,

Madhu Vishnu Sankar Reddy Rami Reddy

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8266 - 8266

Опубликована: Июль 29, 2024

The disruption of brain energy metabolism, leading to alterations in synaptic signaling, neural circuitry, and neuroplasticity, has been implicated severe mental illnesses such as schizophrenia, bipolar disorder, major depressive disorder. therapeutic potential ketogenic interventions these disorders suggests a link between metabolic disturbances disease pathology; however, the precise mechanisms underlying disturbances, effects therapy, remain poorly understood. In this study, we conducted an silico analysis transcriptomic data investigate perturbations pathways across via gene expression profiling. We also examined dysregulation same rodent or cell culture models ketosis, comparing profiles those observed states. Our revealed significant all pathways, with greatest glycolysis, tricarboxylic acid (TCA) cycle, electron transport chain (ETC) three disorders. Additionally, some discordant patterns states intervention studies, suggesting role for ketone bodies modulating pathogenic changes. findings highlight importance understanding benefits restoring homeostasis. This study provides insights into complex relationship metabolism neuropsychiatric lays foundation further experimental investigations aimed at appreciating implications present well developing targeted strategies.

Язык: Английский

βIV spectrin abundancy, cellular distribution and sensitivity to AKT/GSK3 regulation in schizophrenia DOI Creative Commons
Jessica Di Re, Michela Marini, Syed Ibrar Hussain

и другие.

Molecular Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 7, 2025

Schizophrenia (SCZ) is a complex psychiatric disorder with unclear biological mechanisms. Spectrins, cytoskeletal proteins linked to neurodevelopmental disorders, are regulated by the AKT/GSK3 pathway, which implicated in SCZ. However, impact of SCZ-related dysregulation this pathway on spectrin expression and distribution remains unexplored. Here, we show that βIV protein levels were reduced neurons dorsolateral prefrontal cortex SCZ postmortem samples compared healthy control (HC) from Human Brain Collection Core (HBCC). To investigate potential links between analyzed PsychEncode dataset, revealing elevated SPTBN4 AKT2 mRNA correlated gene transcription both HCs individuals Next, computational tools employed identify AKT GSK3 phosphorylation sites spectrin, two validated through vitro assays. assess whether sensitivity altered SCZ, used iPSC-derived independent cohorts patients significantly increased familial genetic risk for disorder. Alteration inhibitors consistently observed across cohorts. Importantly, Random Forest classifier applied imaging achieved up 98% accuracy classifying cells diagnosis samples, or × perturbation iPSC samples. These findings reveal identifying image-based endophenotypes as robust, generalizable predictive biomarkers scalable clinical applications.

Язык: Английский

Процитировано

0
Metabolic Insights into Neuropsychiatric Illnesses and Ketogenic Therapies: A Transcriptomic View DOI Open Access
Smita Sahay, Priyanka Pulvender,

Madhu Vishnu Sankar Reddy Rami Reddy

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8266 - 8266

Опубликована: Июль 29, 2024

The disruption of brain energy metabolism, leading to alterations in synaptic signaling, neural circuitry, and neuroplasticity, has been implicated severe mental illnesses such as schizophrenia, bipolar disorder, major depressive disorder. therapeutic potential ketogenic interventions these disorders suggests a link between metabolic disturbances disease pathology; however, the precise mechanisms underlying disturbances, effects therapy, remain poorly understood. In this study, we conducted an silico analysis transcriptomic data investigate perturbations pathways across via gene expression profiling. We also examined dysregulation same rodent or cell culture models ketosis, comparing profiles those observed states. Our revealed significant all pathways, with greatest glycolysis, tricarboxylic acid (TCA) cycle, electron transport chain (ETC) three disorders. Additionally, some discordant patterns states intervention studies, suggesting role for ketone bodies modulating pathogenic changes. findings highlight importance understanding benefits restoring homeostasis. This study provides insights into complex relationship metabolism neuropsychiatric lays foundation further experimental investigations aimed at appreciating implications present well developing targeted strategies.

Язык: Английский

Процитировано

2