miR-378a-5p regulates CAMKK2/AMPK pathway to contribute to cerebral ischemia/reperfusion injury-induced neuronal apoptosis

Zhang, Yun; Zhang, Peilan; Deng, Chunying

doi:10.5603/fhc.a2021.0007

Cited by 10 publications

(6 citation statements)

References 21 publications

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“…We eventually identified nine candidate miRs, miR-101-3p, miR-378a-3p, miR-21-5p, miR-192-5p and miR-103a-3p, miR-500a-3p, mIR-501-3p, miR-221-5p and miR-99b-5p. Except for miR-99b-5p, all of these miRs have been implicated in brain diseases and neuronal plasticity (Dong et al, 2021 ; Biselli et al, 2022 ; Zhang et al, 2021 ; Banach et al, 2022 ; Barbato et al, 2020 ; Mundalil Vasu et al, 2014 ; Zadehbagheri et al, 2019 ; Maffioletti et al, 2016 ; Qin et al, 2022 ; Yoshino et al, 2021 ; Tang et al, 2019 ; Van der Auwera et al, 2019 ). (Huang et al, 2021 ) and even specifically with SZ (Chen et al, 2016 ; Liu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice

Kaurani,

Islam,

Heilbronner

et al. 2024

EMBO J

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Current approaches to the treatment of schizophrenia have mainly focused on the protein-coding part of the genome; in this context, the roles of microRNAs have received less attention. In the present study, we analyze the microRNAome in the blood and postmortem brains of schizophrenia patients, showing that the expression of miR-99b-5p is downregulated in both the prefrontal cortex and blood of patients. Lowering the amount of miR-99b-5p in mice leads to both schizophrenia-like phenotypes and inflammatory processes that are linked to synaptic pruning in microglia. The microglial miR-99b-5p-supressed inflammatory response requires Z-DNA binding protein 1 (Zbp1), which we identify as a novel miR-99b-5p target. Antisense oligonucleotides against Zbp1 ameliorate the pathological effects of miR-99b-5p inhibition. Our findings indicate that a novel miR-99b-5p-Zbp1 pathway in microglia might contribute to the pathogenesis of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice

Kaurani,

Islam,

Heilbronner

et al. 2024

EMBO J

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“…According to Sun et al, miR-378a-5p remained unchanged 1 d after transient ischemia in gerbils but was upregulated 7 days later [ 8 ], which is consistent with our results. In addition, it has been shown that OGD treatment of hippocampal neurons in newborn rats upregulates miR-378a-5p in a time-dependent manner from 24 h to 48 h; knockdown with an inhibitor promotes cell viability and reduces apoptosis [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Temporal expression profiles of microRNAs associated with acute phase of brain ischemia in gerbil hippocampus

Hamada,

Takata,

Iwama

et al. 2024

Heliyon

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“…For example, knock-down of miR-101-3p in the hippocampus impairs learning in mice 45 while increased circulating levels of miR-101-3p have been observed in patients suffering from autism 46 , attention-deficit hyperactivity disorder 47 but also diabetes 48 49 or cancer 50 . MiR-378a-3p has been associated with cerebral ischemia 51 is increased in blood samples of Down syndrome patients 52 and was reported to be part of a blood-miR signature that can distinguish Alzheimer’s disease patients from control 53 . miR-21-5p was found to be increased in blood samples of SZ patients 29 , while antipsychotic treatment is correlated with decreased miR-21-3p expression 54 .…”

Section: Discussionmentioning

confidence: 99%

A novel miR-99b-5p-Zbp1pathway in microglia contributes to the pathogenesis of schizophrenia

Kaurani

Islam

Heilbronner

et al. 2023

Preprint

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Schizophrenia is a psychiatric disorder that is still not readily treatable. Pharmaceutical advances in the treatment of schizophrenia have mainly focused on the protein coding part of the human genome. However, the vast majority of the human transcriptome consists of non-coding RNAs. MicroRNAs are small non-coding RNAs that control the transcriptome at the systems level. In the present study we analyzed the microRNAome in blood and postmortem brains of controls and schizophrenia patients and found that miR 99b-5p was downregulated in both the prefrontal cortex and blood of patients. At the mechanistic level we show that inhibition of miR-99b-5p leads to schizophrenia-like phenotypes in mice and induced inflammatory processes in microglia linked to synaptic pruning. The miR-99b-5p mediated inflammatory response in microglia depended on Z DNA binding protein 1 (Zbp1) which we identified as a novel miR-99b-5p target. Antisense oligos (ASOs) against Zbp1 ameliorated the pathological phenotypes caused by miR-99b-5p inhibition. In conclusion, we report a novel miR-99b-5p-Zbp1 pathway in microglia that contributes to the pathogenesis of schizophrenia. Our data suggest that strategies to increase the levels of miR-99b-5p or inhibit Zbp1 could become a novel therapeutic strategy.

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miR-378a-5p regulates CAMKK2/AMPK pathway to contribute to cerebral ischemia/reperfusion injury-induced neuronal apoptosis

Cited by 10 publications

References 21 publications

Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice

Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice

Temporal expression profiles of microRNAs associated with acute phase of brain ischemia in gerbil hippocampus

A novel miR-99b-5p-Zbp1pathway in microglia contributes to the pathogenesis of schizophrenia

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