Saikosaponin A Alleviates Symptoms of Attention Deficit Hyperactivity Disorder through Downregulation of DAT and Enhancing BDNF Expression in Spontaneous Hypertensive Rats.

Sun Jichao,Ren Xianguo,Zhou Rongyi,Lei Shuang,Ying Jingnan,Han Xinmin,Song Yuchen,Yin Dongqi,You Yue

doi:10.1155/2017/2695903

Abstract

The disturbed dopamine availability and brain-derived neurotrophic factor (BDNF) expression are due in part to be associated with attention deficit hyperactivity disorder (ADHD). In this study, we investigated the therapeutical effect of saikosaponin a (SSa) isolated from Bupleurum Chinese DC, against spontaneously hypertensive rat (SHR) model of ADHD. Methylphenidate and SSa were orally administered for 3 weeks. Activity was assessed by open-field test and Morris water maze test. Dopamine (DA) and BDNF were determined in specific brain regions. The mRNA or protein expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicles monoamine transporter (VMAT) was also studied. Both MPH and SSa reduced hyperactivity and improved the spatial learning memory deficit in SHRs. An increased DA concentration in the prefrontal cortex (PFC) and striatum was also observed after treating with the SSa. The increased DA concentration may partially be attributed to the decreased mRNA and protein expression of DAT in PFC while SSa exhibited no significant effects on the mRNA expression of TH and VMAT in PFC of SHRs. In addition, BDNF expression in SHRs was also increased after treating with SSa or MPH. The obtained result suggested that SSa may be a potential drug for treating ADHD.

Highlights

Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopment disorder characterized by a persistent of inattention, hyperactivity, and/or increased impulsivity, pervasive across setting, and this may lead to various degrees of functional impairment [1]
In accordance with the previous studies, spontaneously hypertensive rat (SHR) were more active than WKY rats
After treating test drugs one week later, moving distance (p < 0.05) and rearing (p < 0.01) in SHRs treated with MPH were reduced as compared to saline-treated SHRs

Summary

Introduction

Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopment disorder characterized by a persistent of inattention, hyperactivity, and/or increased impulsivity, pervasive across setting, and this may lead to various degrees of functional impairment [1]. According to the Diagnostic and Statistical Manual (DSM-5), three subtypes have been identified: predominantly hyperactivity/impulsive type, predominantly inattentive type, and combined type. It is a major clinical and public health problem as individuals suffering ADHD have much higher incidence of cocaine abuse when comparing with age matched healthy individuals [3, 4]. Previous work revealed that no single risk factor is either necessary or sufficient to explain ADHD, which indicated that many genetic and nongenetic (or environment) factors, including genetic, heredity, gene-environment interplay, and environment, may be involved in the occurrence and development of the ADHD [6,7,8,9]. It is widely accepted that dysfunction of catecholamine and particular dopamine (DA) neuronal

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