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Cited by 42MicroRNA in disease regulationNeurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatment

miR-124 dosage regulates prefrontal cortex function by dopaminergic modulation

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Kozuka, Takashi, Omori, Yoshihiro, Watanabe, Satoshi, Tarusawa, Etsuko, Yamamoto, Haruka, Chaya, Taro, Furuhashi, Mayu, Morita, Makiko +6 more·2019·Scientific Reports
DOI 10.1038/s41598-019-38910-2PMC PMC6401137
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Abstract

MicroRNA-124 (miR-124) is evolutionarily highly conserved among species and one of the most abundantly expressed miRNAs in the developing and mature central nervous system (CNS). Previous studies reported that miR-124 plays a role in CNS development, such as neuronal differentiation, maturation, and survival. However, the role of miR-124 in normal brain function has not yet been revealed. Here, we subjected miR-124-1+/− mice, to a comprehensive behavioral battery. We found that miR-124-1+/− mice showed impaired prepulse inhibition (PPI), methamphetamine-induced hyperactivity, and social deficits. Whole cell recordings using prefrontal cortex (PFC) slices showed enhanced synaptic transmission in layer 5 pyramidal cells in the miR-124-1+/− PFC. Based on the results of behavioral and electrophysiological analysis, we focused on genes involved in the dopaminergic system and identified a significant increase of Drd2 expression level in the miR-124-1+/− PFC. Overexpression or knockdown of Drd2 in the control or miR-124-1+/− PFC demonstrates that aberrant Drd2 signaling leads to impaired PPI. Furthermore, we identified that expression of glucocorticoid receptor gene Nr3c1, which enhances Drd2 expression, increased in the miR-124-1+/− PFC. Taken together, the current study suggests that miR-124 dosage modulates PFC function through repressing the Drd2 pathway, suggesting a critical role of miR-124 in normal PFC function.

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  • miR-124 is associated with neuronal function and APP processing.

    “Among these, miR-125b is associated with Tau phosphorylation [30], miR-124 with neuronal function and APP processing [25,31], and miR-21 to the regulation of toxicity mediated by Aβ oligomers, both in vitro and in vivo [32].”

    From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [31]

    The Introduction and Abstract link miR-124 to neuronal development and prefrontal cortex function. The paper does not establish a role for miR-124 in APP processing; APP appears only in a cited reference on neuronal splicing. Thus it supports the neuronal-function part of the attributed claim, but not the APP-processing part. (LLM, conf=0.86)

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Authors
Kozuka, T., Omori, Y., Watanabe, S., Tarusawa, E., Yamamoto, H., Chaya, T., Furuhashi, M., Morita, M., Sato, T., Hirose, S., Ohkawa, Y., Yoshimura, Y., Hikida, T., & Furukawa, T.
Affiliations
  • Japan Science and Technology Agency (JP)
  • National Institutes of Natural Sciences (JP)
  • Institute for Protein Research, The University of Osaka (JP)
  • Kyoto University (JP)
  • Kyushu University (JP)
  • Fukuoka University (JP)
Corresponding author
Furukawa, Takahisa
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-03-05
Volume
9
Issue
1
Pages
3445-3445
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-38910-2
PMC
PMC6401137
OpenAlex
W2922515674
Cited by
42
References
5
Citations by year
2025: 9 · 2024: 3 · 2023: 7 · 2022: 8 · 2021: 7 · 2020: 8
FWCI
1.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
Funders
  • Suzuken Memorial Foundation
  • Takeda Science Foundation
  • Sumitomo Foundation
  • Uehara Memorial Foundation (CREST)
  • Mitsui Sumitomo Insurance Welfare Foundation
  • Senri Life Science Foundation
  • Kanae Foundation for the Promotion of Medical Science
  • Japan Society for the Promotion of Science (15H04275, 18H02593, 18H04802, 16K08583, 25670481, 17H03608, 18K14611, 17K19356, 17K15548, 16K15532, CREST, 15H04669, 19H03420, 16K14579, 18H02542, 15H02548, 16H06568, 25116010)
  • Core Research for Evolutional Science and Technology
  • National Institute for Physiological Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
miR-124, prefrontal cortex, prepulse inhibition, dopaminergic system, dopamine D1 receptor, DRD2, glucocorticoid receptor, NR3C1, synaptic transmission, layer 5 pyramidal cells, social dysfunction
MeSH terms
Animals, Behavior, Animal, Disease Models, Animal, Dopamine, Gene Expression Regulation, Synaptic Transmission, Prefrontal Cortex, Pyramidal Cells, Mice, Knockout, 3' Untranslated Regions, RNA Interference, MicroRNAs, Mice, Sensory Gating, Haploinsufficiency, Dopaminergic Neurons

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