Effects of Aberrant miR-384-5p Expression on Learning and Memory in a Rat Model of Attention Deficit Hyperactivity Disorder.

Qu Xu,Qingyu Zhang,Xirong Guo,Lei Yang,Jiaxin Ou,Ranran Tang,Jing Wang,Xia Chi,Qin Hong,Meiling Tong

doi:10.3389/fneur.2019.01414

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder characterized by inattention, hyperactivity, and impulsivity. It may be accompanied by learning difficulties and working memory deficits. Few studies have examined the role of miRNAs in cognitive dysfunction in ADHD. This study investigated the effects of aberrant miR-384-5p expression on learning and memory in a widely used ADHD rat model. Lentiviral vectors were injected into the lateral ventricles of the rats to increase or decrease miR-384-5p level. To determine whether aberrant miR-384-5p expression affects learning and memory, spontaneous activity and cognitive function were assessed with the open field and Morris water maze tests. In the place navigation experiment of the Morris water maze test, time, and total swimming distance to reach the platform decreased compared to the control group when miR-384-5p was overexpressed, whereas down-regulation of miR-384-5p had the opposite effect. There were no obvious changes in brain tissue morphology following miR-384-5p overexpression or inhibition; however, dopamine (DA) receptor D1 (DRD1) level has decreased and increased, respectively, in the prefrontal cortex (PFC). The luciferase activity of the wild-type DRD1 group has decreased in luciferase reporter assay. Cyclic AMP response element-binding protein (CREB) phosphorylation has increased, and DA transporter (DAT) level has decreased in the PFC of spontaneously hypertensive rats (SHR) by miR-384-5p overexpression. On the other hand, miR-384-5p suppression increased DRD1 and decreased DAT and CREB protein levels relative to control rats. These findings suggest that miR-384-5p may play a critical role in learning and memory impairment in ADHD.

Highlights

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that begins in childhood [1] and affects around 5% of children and adolescents [2]
We showed that aberrant miR-3845p expression affected learning and memory in spontaneously hypertensive rats (SHR) rats
To investigate the underlying mechanisms, we examined the expression of cognition-associated genes in specific brain regions, namely, the Hip, prefrontal cortex (PFC), and Str

Summary

INTRODUCTION

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that begins in childhood [1] and affects around 5% of children and adolescents [2]. MiRNAs modulate cellular functions and participate in cell fate specification, neuronal survival, neurite projection, and synaptic plasticity [12]. The cognitive behavior of rats is regulated by the miRNA miR-124 or miR-9 [21], and miR-335-5p was found to modulate spatial memory and hippocampal synaptic plasticity [22]. There are few studies on the role of miRNAs in learning and memory, especially in the context of ADHD. Its role in learning and memory impairment in ADHD has not yet been reported. To address this issue, the present study investigated the function and mechanism of action of miR-384-5p in spontaneously hypertensive (SHR) rats, which is a frequently used animal model of ADHD

EXPERIMENTAL PROCEDURES

RESULTS

DISCUSSION

ETHICS STATEMENT