MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro

Research output: Contribution to journalJournal articleResearchpeer-review

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MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro. / Bin Wei, Ya; Melas, Philippe A.; Villaescusa, J. Carlos; Liu, Jia Jia; Xu, Ning; Christiansen, Soren Hofman; Elbrønd-Bek, Heidi; Woldbye, David Paul Drucker; Wegener, Gregers; Mathe, Aleksander A.; Lavebratt, Catharina.

In: International Journal of Neuropsychopharmacology, Vol. 19, No. 12, pyw069, 12.2016.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Bin Wei, Y, Melas, PA, Villaescusa, JC, Liu, JJ, Xu, N, Christiansen, SH, Elbrønd-Bek, H, Woldbye, DPD, Wegener, G, Mathe, AA & Lavebratt, C 2016, 'MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro', International Journal of Neuropsychopharmacology, vol. 19, no. 12, pyw069. https://doi.org/10.1093/ijnp/pyw069

APA

Bin Wei, Y., Melas, P. A., Villaescusa, J. C., Liu, J. J., Xu, N., Christiansen, S. H., ... Lavebratt, C. (2016). MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro. International Journal of Neuropsychopharmacology, 19(12), [pyw069]. https://doi.org/10.1093/ijnp/pyw069

Vancouver

Bin Wei Y, Melas PA, Villaescusa JC, Liu JJ, Xu N, Christiansen SH et al. MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro. International Journal of Neuropsychopharmacology. 2016 Dec;19(12). pyw069. https://doi.org/10.1093/ijnp/pyw069

Author

Bin Wei, Ya ; Melas, Philippe A. ; Villaescusa, J. Carlos ; Liu, Jia Jia ; Xu, Ning ; Christiansen, Soren Hofman ; Elbrønd-Bek, Heidi ; Woldbye, David Paul Drucker ; Wegener, Gregers ; Mathe, Aleksander A. ; Lavebratt, Catharina. / MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro. In: International Journal of Neuropsychopharmacology. 2016 ; Vol. 19, No. 12.

Bibtex

@article{5d82460c74304d10ad0e7411664f82be,
title = "MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro",
abstract = "Background:MicroRNAs (miRNAs) are small regulatory molecules that cause translational repression by base pairing with target mRNAs. Cumulative evidence suggests that changes in miRNA expression may in part underlie the pathophysiology and treatment of neuropsychiatric disorders, including major depressive disorder (MDD).Methods:A miRNA expression assay that can simultaneously detect 423 rat miRNAs (miRBase v.17) was used to profile the prefrontal cortex (PFC) of a genetic rat model of MDD (the Flinders Sensitive Line [FSL]) and the controls, the Flinders Resistant Line (FRL). Gene expression data from the PFC of FSL/FRL animals (GEO accession no. GSE20388) were used to guide mRNA target selection. Luciferase reporter assays were used to verify miRNA targets in vitro.Results:We identified 23 miRNAs that were downregulated in the PFC of the FSL model compared with controls. Interestingly, one of the identified miRNAs (miR-101b) is highly conserved between rat and human and was recently found to be downregulated in the PFC of depressed suicide subjects. Using a combination of in silico and in vitro analyses, we found that miR-101b targets the neuronal glutamate transporter SLC1A1 (also known as EAAC1 or EAAT3). Accordingly, both mRNA and protein levels of SLC1A1 were found to be upregulated in the PFC of the FSL model.Conclusions:Besides providing a list of novel miRNAs associated with depression-like states, this preclinical study replicated the human association of miR-101 with depression. In addition, since one of the targets of miR-101b appears to be a glutamate transporter, our preclinical data support the hypothesis of a glutamatergic dysregulation being implicated in the etiology of depression.",
keywords = "epigenetics, miRNA, depression, EAAC1, DCBXA",
author = "{Bin Wei}, Ya and Melas, {Philippe A.} and Villaescusa, {J. Carlos} and Liu, {Jia Jia} and Ning Xu and Christiansen, {Soren Hofman} and Heidi Elbr{\o}nd-Bek and Woldbye, {David Paul Drucker} and Gregers Wegener and Mathe, {Aleksander A.} and Catharina Lavebratt",
year = "2016",
month = "12",
doi = "10.1093/ijnp/pyw069",
language = "English",
volume = "19",
journal = "International Journal of Neuropsychopharmacology",
issn = "1461-1457",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro

AU - Bin Wei, Ya

AU - Melas, Philippe A.

AU - Villaescusa, J. Carlos

AU - Liu, Jia Jia

AU - Xu, Ning

AU - Christiansen, Soren Hofman

AU - Elbrønd-Bek, Heidi

AU - Woldbye, David Paul Drucker

AU - Wegener, Gregers

AU - Mathe, Aleksander A.

AU - Lavebratt, Catharina

PY - 2016/12

Y1 - 2016/12

N2 - Background:MicroRNAs (miRNAs) are small regulatory molecules that cause translational repression by base pairing with target mRNAs. Cumulative evidence suggests that changes in miRNA expression may in part underlie the pathophysiology and treatment of neuropsychiatric disorders, including major depressive disorder (MDD).Methods:A miRNA expression assay that can simultaneously detect 423 rat miRNAs (miRBase v.17) was used to profile the prefrontal cortex (PFC) of a genetic rat model of MDD (the Flinders Sensitive Line [FSL]) and the controls, the Flinders Resistant Line (FRL). Gene expression data from the PFC of FSL/FRL animals (GEO accession no. GSE20388) were used to guide mRNA target selection. Luciferase reporter assays were used to verify miRNA targets in vitro.Results:We identified 23 miRNAs that were downregulated in the PFC of the FSL model compared with controls. Interestingly, one of the identified miRNAs (miR-101b) is highly conserved between rat and human and was recently found to be downregulated in the PFC of depressed suicide subjects. Using a combination of in silico and in vitro analyses, we found that miR-101b targets the neuronal glutamate transporter SLC1A1 (also known as EAAC1 or EAAT3). Accordingly, both mRNA and protein levels of SLC1A1 were found to be upregulated in the PFC of the FSL model.Conclusions:Besides providing a list of novel miRNAs associated with depression-like states, this preclinical study replicated the human association of miR-101 with depression. In addition, since one of the targets of miR-101b appears to be a glutamate transporter, our preclinical data support the hypothesis of a glutamatergic dysregulation being implicated in the etiology of depression.

AB - Background:MicroRNAs (miRNAs) are small regulatory molecules that cause translational repression by base pairing with target mRNAs. Cumulative evidence suggests that changes in miRNA expression may in part underlie the pathophysiology and treatment of neuropsychiatric disorders, including major depressive disorder (MDD).Methods:A miRNA expression assay that can simultaneously detect 423 rat miRNAs (miRBase v.17) was used to profile the prefrontal cortex (PFC) of a genetic rat model of MDD (the Flinders Sensitive Line [FSL]) and the controls, the Flinders Resistant Line (FRL). Gene expression data from the PFC of FSL/FRL animals (GEO accession no. GSE20388) were used to guide mRNA target selection. Luciferase reporter assays were used to verify miRNA targets in vitro.Results:We identified 23 miRNAs that were downregulated in the PFC of the FSL model compared with controls. Interestingly, one of the identified miRNAs (miR-101b) is highly conserved between rat and human and was recently found to be downregulated in the PFC of depressed suicide subjects. Using a combination of in silico and in vitro analyses, we found that miR-101b targets the neuronal glutamate transporter SLC1A1 (also known as EAAC1 or EAAT3). Accordingly, both mRNA and protein levels of SLC1A1 were found to be upregulated in the PFC of the FSL model.Conclusions:Besides providing a list of novel miRNAs associated with depression-like states, this preclinical study replicated the human association of miR-101 with depression. In addition, since one of the targets of miR-101b appears to be a glutamate transporter, our preclinical data support the hypothesis of a glutamatergic dysregulation being implicated in the etiology of depression.

KW - epigenetics

KW - miRNA

KW - depression

KW - EAAC1

KW - DCBXA

U2 - 10.1093/ijnp/pyw069

DO - 10.1093/ijnp/pyw069

M3 - Journal article

VL - 19

JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

SN - 1461-1457

IS - 12

M1 - pyw069

ER -

ID: 174037817