Nr3C1-Bhlhb2 Axis Dysregulation Is Involved in the Development of Attention Deficit Hyperactivity

Molecular Neurobiology
Li Hui WuXing Zhong Wu

Abstract

Attention deficit hyperactivity disorder (ADHD) is a child developmental and behavioral disorder which seriously hinders their education and development. To investigate the key regulators in the prefrontal cortex (PFC), the major affected areas of ADHD, microRNA (miR)-138,138*, 34c*, 296, and 494, were noted for their significant downregulation in ADHD model rats spontaneously hypertensive rats (SHRs) compared to Wistar Kyoto (WKY) rat control. Based on promoter sequence analysis and activity assay, glucocorticoid receptor (Nr3c1) was identified for the inhibition of the promoter activity of miR-138-1, 34c*, 296, and 494 genes and their transcription. In the PFC of ADHD model rats SHR, Nr3c1 expression was abnormally elevated and reversely correlated with the levels of miR-138-1, 34c, 296, and 494 expression. Luciferase report assays indicated that all miR-138, 138*, 34c*, 296, and 494 targeted the 3' untranslated region of transcription factor Bhlhb2 (Bhlhe40) messenger RNA (mRNA) in common and ectopic expression of miR-138,138*, 34c*, 296, and 494 further suppressed the expression of Bhlhb2 gene. Consistently, Bhlhb2 expression was significantly higher in PFC of ADHD model SHR than control. Overexpressed Bhlhb2 in vitro signi...Continue Reading

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Citations

May 12, 2017·Attention Deficit and Hyperactivity Disorders·Saurabh SrivastavEdna Grünblatt
Mar 29, 2021·Journal of Molecular Neuroscience : MN·Iman Imtiyaz Ahmed Juvale, Ahmad Tarmizi Che Has
May 15, 2021·Frontiers in Cell and Developmental Biology·Lu ZhaoZhengwei Yuan

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Methods Mentioned

BETA
PCR
electrophoresis
Assay
immunoprecipitation
ELISA
transfection
transfect

Software Mentioned

microCosm
TargetScan
Pictar
ImageJ

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