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- Title
A Novel Function of MicroRNA Let-7d in Regulation of Galectin-3 Expression in Attention Deficit Hyperactivity Disorder Rat Brain.
- Authors
Lihui Wu; Qianlei Zhao; Xuchao Zhu; Min Peng; Chenyou Jia; Wei Wu; Jing Zheng; Xing Zhong Wu
- Abstract
In this study we investigated the locomotor activity and non-selective attention in spontaneously hypertensive rats (SHR) with control Wistar-Kyoto (WKY) rats, which were employed as an attention deficit hyperactivity disorder (ADHD) model. In open-field test and làt maze, SHR rats were found to be much more spontaneously active than WKY rats. As compared with WKY rats, a lower level of galectin-3 was observed in SHR brain prefrontal cortex (PFC), which was the major affected brain area of ADHD. Through miRNA microarray screening, rno-let-7d was noted to be solely upregulated in SHR PFC. Interestingly, rno-let-7d had a binding site at galectin-3 mRNA and was shown to regulate galectin-3 3′ untranslated region (UTR) directly. Mutation of galectin-3 3′UTR by one nucleotide of the seed sequence prevented rno-let-7d regulation of the 3′ UTR completely. Although rno-let-7d did not directly regulate tyrosine hydroxylase (TH) 3′UTR, the level of galectin-3 was important for cAMP response element binding protein, the major transcript factor for TH gene. Either overexpression or downexpression of galectin-3 could result in modulation of TH expression in both PC12H and PC12L cells. In conclusion, our data suggested a novel function of rno-let-7d in regulation of galectin-3 and in ADHD development. Rno-let-7d, which is increased in the PFC of SHR brain, negatively regulated galectin-3, which is coupled with TH expression regulation.
- Subjects
ATTENTION-deficit hyperactivity disorder; NUCLEOTIDE sequence; TYROSINE; CARRIER protein genetics; LABORATORY rats; GENETICS
- Publication
Brain Pathology, 2010, Vol 20, Issue 6, p1042
- ISSN
1015-6305
- Publication type
Article
- DOI
10.1111/j.1750-3639.2010.00410.x