miR-124 dosage regulates prefrontal cortex function by dopaminergic modulation.
Sci Rep
; 9(1): 3445, 2019 03 05.
Article
em En
| MEDLINE
| ID: mdl-30837489
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dopamina
/
Córtex Pré-Frontal
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MicroRNAs
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Neurônios Dopaminérgicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article