期刊
SCIENTIFIC REPORTS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-38910-2
关键词
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资金
- JST-CREST [09154509, PMJCR16G1]
- Japan Society for the Promotion of Science (JSPS) [15H04669, 18H02593, 16K08583, 16H06568, 16K14579, 15H04275, 15H02548, 25116010, 17K15548]
- JSPS
- Takeda Science Foundation
- Uehara Memorial Foundation
- Senri Life Science Foundation
- Sumitomo Foundation
- KANAE Foundation for the Promotion of Medical Science
- Suzuken Memorial Foundation
- Mitsui Sumitomo Insurance Welfare Foundation
- Terumo Foundation for Life Science and Arts
- [25670481]
- [16K15532]
- Grants-in-Aid for Scientific Research [16H06568, 17K15548, 15H04669, 16K08583, 16K14579] Funding Source: KAKEN
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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