A rare MIR138-2 gene variation is associated with schizophrenia in a Japanese population

Watanabe, Yuichiro; Hishimoto, Akitoyo; Shibuya, Masako; Nunokawa, Ayako; Kaneko, Naoshi; Igeta, Hirofumi; Egawa, Jun; Mouri, Kentaro; Sora, Ichiro; Someya, Toshiyuki

doi:10.1016/j.psychres.2013.12.029

Cited by 5 publications

(4 citation statements)

References 6 publications

(6 reference statements)

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“…Thus, the observed lack of regulation of miR138-5p targets in excitatory pyramidal neurons of 138-sponge Ub mice is likely a result of inefficient sponge-mediated miR138-5p inhibition in this cell type. Since miR138-5p and alterations in PV+ interneuron function had recently been linked to SCZ ( Pelkey et al, 2017 ; Watanabe et al, 2014 ), we performed a comparison between DEGs from 138-sponge ub mouse hippocampus and cortical tissue of SCZ patients ( Gandal et al, 2018 ). We found a significant overlap between genes upregulated in the 138-sponge ub hippocampus and SCZ patients (p=0.00884; Figure 4—figure supplement 1d ).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, GWAS analysis identified miR138-5p as a putative regulator of human memory performance ( Schröder et al, 2014 ). A rare miR-138-2 gene variation is furthermore associated with SCZ in a Japanese population ( Watanabe et al, 2014 ), and miR138-5p levels are altered in the superior temporal gyrus and dorsolateral prefrontal cortex of SCZ patients ( Beveridge et al, 2010 ; Moreau et al, 2011 ). Finally, several miR138-5p targets have been genetically linked to SCZ (e.g., Erbb4, Drd2, and Igsf9b ) ( Kumar et al, 2010 ; Nicodemus et al, 2006 ) or are deregulated in the cortex of SCZ patients (e.g., Gabra3, Fxyd6, Tmem132c , and Baiap3 , Gandal et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice

Daswani

Gilardi

Soutschek

et al. 2022

eLife

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The proper development and function of neuronal circuits relies on a tightly regulated balance between excitatory and inhibitory (E/I) synaptic transmission, and disrupting this balance can cause neurodevelopmental disorders, e.g. schizophrenia. microRNA-dependent gene regulation in pyramidal neurons is important for excitatory synaptic function and cognition, but its role in inhibitory interneurons is poorly understood. Here, we identify miR138-5p as a regulator of short-term memory and inhibitory synaptic transmission in the mouse hippocampus. Sponge-mediated miR138-5p inactivation specifically in mouse parvalbumin (PV)-expressing interneurons impairs spatial recognition memory and enhances GABAergic synaptic input onto pyramidal neurons. Cellular and behavioural phenotypes associated with miR138-5p inactivation are paralleled by an upregulation of the schizophrenia-associated Erbb4, which we validated as a direct miR138-5p target gene. Our findings suggest that miR138-5p is a critical regulator of PV interneuron function in mice, with implications for cognition and schizophrenia. More generally, they provide evidence that microRNAs orchestrate neural circuit development by fine-tuning both excitatory and inhibitory synaptic transmission.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice

Daswani

Gilardi

Soutschek

et al. 2022

eLife

View full text Add to dashboard Cite

show abstract

“…Thus, the observed lack of regulation of miR-138-5p targets in excitatory pyramidal neurons of 138-sponge Ub mice is likely a result of inefficient sponge-mediated miR-138-5p inhibition in this cell type. Since miR-138-5p and alterations in PV+ interneuron function had recently been linked to schizophrenia (SCZ) (Pelkey et al, 2017; Watanabe et al, 2014), we performed a comparison between DEGs from 138-sponge ub mouse hippocampus and cortical tissue of SCZ patients (Gandal et al, 2018). We found a significant overlap between genes upregulated in the 138-sponge ub hippocampus and SCZ patients (p=0.00884; suppl.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, GWAS analysis identified miR-138-5p as a putative regulator of human memory performance (Schroder et al, 2014). A rare miR-138-2 gene variation is furthermore associated with SCZ in a Japanese population (Watanabe et al, 2014), and miR-138-5p levels are altered in the superior temporal gyrus and dorsolateral prefrontal cortex of SCZ patients (Beveridge et al, 2010) (Moreau et al, 2011). Finally, several miR-138-5p targets have been genetically linked to SCZ (e.g.…”

Section: Discussionmentioning

confidence: 99%

microRNA-138 controls hippocampal interneuron function and short-term memory

Daswani¹,

Gilardi²,

Soutschek³

et al. 2021

Preprint

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A tightly regulated balance between excitatory and inhibitory (E/I) synaptic transmission is critical for neural circuit assembly and function. microRNAs control excitatory neuron function, but their role in inhibitory interneurons is unknown. Here, we show that miR-138-5p regulates the expression of presynaptic genes in hippocampal parvalbumin-expressing inhibitory interneurons to control short-term memory. Our finding suggests a critical role for miR-138-5p in disorders of impaired E/I balance, such as autism and schizophrenia.

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Epigenetic biomarkers in neuropsychiatric disorders

Lin

Huang

2017

Neuropsychiatric Disorders and Epigenetics

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A rare MIR138-2 gene variation is associated with schizophrenia in a Japanese population

Cited by 5 publications

References 6 publications

MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice

MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice

microRNA-138 controls hippocampal interneuron function and short-term memory

Epigenetic biomarkers in neuropsychiatric disorders

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