miR-19b is elevated in peripheral blood of schizophrenic patients and attenuates proliferation of hippocampal neural progenitor cells

Horai, Tadasu; Boku, Shuken; Okazaki, Satoshi; Otsuka, Ikuo; Ratta‐apha, Woraphat; Mouri, Kentaro; Yamaki, Naruhisa; Hirata, Takashi; Hishimoto, Akitoyo

doi:10.1016/j.jpsychires.2020.09.006

Cited by 6 publications

(4 citation statements)

References 43 publications

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“…Still, the diagnostic value of serum miRNA detection remains controversial, as miRNAs show strong pleiotropy. For example, miR-19b has also been implicated in lung cancer progression [ 195 ] and schizophrenia [ 196 ]. One study revealed decreased antioxidant superoxide dismutase and increased glycolysis in iRBD cases using peripheral blood mononuclear cells [ 197 ].…”

Section: Prodromal Pd As a Clinical Surrogate For Early Pathological ...mentioning

confidence: 99%

Neuropathology of incidental Lewy body & prodromal Parkinson’s disease

Koeglsperger,

Rumpf,

Schließer

et al. 2023

Mol Neurodegeneration

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Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with a loss of dopaminergic (DA) neurons. Despite symptomatic therapies, there is currently no disease-modifying treatment to halt neuronal loss in PD. A major hurdle for developing and testing such curative therapies results from the fact that most DA neurons are already lost at the time of the clinical diagnosis, rendering them inaccessible to therapy. Understanding the early pathological changes that precede Lewy body pathology (LBP) and cell loss in PD will likely support the identification of novel diagnostic and therapeutic strategies and help to differentiate LBP-dependent and -independent alterations. Several previous studies identified such specific molecular and cellular changes that occur prior to the appearance of Lewy bodies (LBs) in DA neurons, but a concise map of such early disease events is currently missing. Methods Here, we conducted a literature review to identify and discuss the results of previous studies that investigated cases with incidental Lewy body disease (iLBD), a presumed pathological precursor of PD. Results Collectively, our review demonstrates numerous cellular and molecular neuropathological changes occurring prior to the appearance of LBs in DA neurons. Conclusions Our review provides the reader with a summary of early pathological events in PD that may support the identification of novel therapeutic and diagnostic targets and aid to the development of disease-modifying strategies in PD.

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Section: Prodromal Pd As a Clinical Surrogate For Early Pathological ...mentioning

confidence: 99%

Neuropathology of incidental Lewy body & prodromal Parkinson’s disease

Koeglsperger,

Rumpf,

Schließer

et al. 2023

Mol Neurodegeneration

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“…Consistent with the negative correlation between hsa-miR-19b-3p and PANSS total scores, Horai et al found that Brief Psychiatric Rating Scale total score [87] had a negative regression coefficient in the estimation of serum miR-19b levels in schizophrenia patients [88]. Horai et al suggested that miR-19b may be involved in the proliferation of neural progenitor cells in the hippocampus of schizophrenia patients [88]. Individual miRNAs, as well as miRNA-based subgroups, may offer an insight into understanding the underlying mechanism of symptoms.…”

Section: Plasma Mirnas Are a Potential Biomarker To Stratify Schizoph...mentioning

confidence: 80%

“…We found that hsa-miR-17-5p, hsa-miR-18b-5p, and hsa-miR-19b-3p were negatively correlated with PANSS total scores, and hsa-miR-30e-5p was negatively correlated with PANSS negative symptom subscales (Table S2 and Figure S2). Consistent with the negative correlation between hsa-miR-19b-3p and PANSS total scores, Horai et al found that Brief Psychiatric Rating Scale total score [87] had a negative regression coefficient in the estimation of serum miR-19b levels in schizophrenia patients [88]. Horai et al suggested that miR-19b may be involved in the proliferation of neural progenitor cells in the hippocampus of schizophrenia patients [88].…”

Section: Plasma Mirnas Are a Potential Biomarker To Stratify Schizoph...mentioning

confidence: 89%

Circulating microRNA Profiles Identify a Patient Subgroup with High Inflammation and Severe Symptoms in Schizophrenia Experiencing Acute Psychosis

Miyano,

Mikkaichi,

Nakamura

et al. 2024

IJMS

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Schizophrenia is a complex and heterogenous psychiatric disorder. This study aimed to demonstrate the potential of circulating microRNAs (miRNAs) as a clinical biomarker to stratify schizophrenia patients and to enhance understandings of their heterogenous pathophysiology. We measured levels of 179 miRNA and 378 proteins in plasma samples of schizophrenia patients experiencing acute psychosis and obtained their Positive and Negative Syndrome Scale (PANSS) scores. The plasma miRNA profile revealed three subgroups of schizophrenia patients, where one subgroup tended to have higher scores of all the PANSS subscales compared to the other subgroups. The subgroup with high PANSS scores had four distinctively downregulated miRNAs, which enriched ‘Immune Response’ according to miRNA set enrichment analysis and were reported to negatively regulate IL-1β, IL-6, and TNFα. The same subgroup had 22 distinctively upregulated proteins, which enriched ‘Cytokine-cytokine receptor interaction’ according to protein set enrichment analysis, and all the mapped proteins were pro-inflammatory cytokines. Hence, the subgroup is inferred to have comparatively high inflammation within schizophrenia. In conclusion, miRNAs are a potential biomarker that reflects both disease symptoms and molecular pathophysiology, and identify a patient subgroup with high inflammation. These findings provide insights for the precision medicinal strategies for anti-inflammatory treatments in the high-inflammation subgroup of schizophrenia.

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“…Recently, miR-19 has been indicated as a major hub for abnormal cellular phenotypes manifested in SZ ( Balan et al, 2019 ). Interestingly, miR-19b, but not miR-19a, is elevated in peripheral blood of SZ patients ( Horai et al, 2020 ).…”

Section: The Role Of Micrornas (Mirnas) In Sz: the Cases Of Mir-137 A...mentioning

confidence: 99%

It takes two to tango: Widening our understanding of the onset of schizophrenia from a neuro-angiogenic perspective

Casas

Arancibia-Altamirano

Rosa

et al. 2022

Front. Cell Dev. Biol.

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Schizophrenia is a chronic debilitating mental disorder characterized by perturbations in thinking, perception, and behavior, along with brain connectivity deficiencies, neurotransmitter dysfunctions, and loss of gray brain matter. To date, schizophrenia has no cure and pharmacological treatments are only partially efficacious, with about 30% of patients describing little to no improvement after treatment. As in most neurological disorders, the main descriptions of schizophrenia physiopathology have been focused on neural network deficiencies. However, to sustain proper neural activity in the brain, another, no less important network is operating: the vast, complex and fascinating vascular network. Increasing research has characterized schizophrenia as a systemic disease where vascular involvement is important. Several neuro-angiogenic pathway disturbances have been related to schizophrenia. Alterations, ranging from genetic polymorphisms, mRNA, and protein alterations to microRNA and abnormal metabolite processing, have been evaluated in plasma, post-mortem brain, animal models, and patient-derived induced pluripotent stem cell (hiPSC) models. During embryonic brain development, the coordinated formation of blood vessels parallels neuro/gliogenesis and results in the structuration of the neurovascular niche, which brings together physical and molecular signals from both systems conforming to the Blood-Brain barrier. In this review, we offer an upfront perspective on distinctive angiogenic and neurogenic signaling pathways that might be involved in the biological causality of schizophrenia. We analyze the role of pivotal angiogenic-related pathways such as Vascular Endothelial Growth Factor and HIF signaling related to hypoxia and oxidative stress events; classic developmental pathways such as the NOTCH pathway, metabolic pathways such as the mTOR/AKT cascade; emerging neuroinflammation, and neurodegenerative processes such as UPR, and also discuss non-canonic angiogenic/axonal guidance factor signaling. Considering that all of the mentioned above pathways converge at the Blood-Brain barrier, reported neurovascular alterations could have deleterious repercussions on overall brain functioning in schizophrenia.

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miR-19b is elevated in peripheral blood of schizophrenic patients and attenuates proliferation of hippocampal neural progenitor cells

Cited by 6 publications

References 43 publications

Neuropathology of incidental Lewy body & prodromal Parkinson’s disease

Neuropathology of incidental Lewy body & prodromal Parkinson’s disease

Circulating microRNA Profiles Identify a Patient Subgroup with High Inflammation and Severe Symptoms in Schizophrenia Experiencing Acute Psychosis

It takes two to tango: Widening our understanding of the onset of schizophrenia from a neuro-angiogenic perspective

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