High sucrose consumption during pregnancy induced ADHD-like behavioral phenotypes in mice offspring

J Nutr Biochem. 2015 Dec;26(12):1520-6. doi: 10.1016/j.jnutbio.2015.07.018. Epub 2015 Aug 8.

Abstract

In recent years, the average consumption of sugar in humans from all ages has remarkably increased, exceeding the recommended limit. Pregnancy is a critical time for the global development of offsprings who are vulnerable to the deleterious effects of environmental factors. In this study, we investigated whether high sucrose consumption during pregnancy could affect the attention-deficit hyperactivity disorder (ADHD)-like neurobehavioral outcomes in offspring mice. Pregnant mice were randomly grouped and orally administered with either water as control (Con) or 30% wt/vol sucrose diluted in water at 6 (Suc6) or 9 (Suc9) g/kg dosage per day from gestational days 6 to 15. After the weaning period, offspring mice underwent a series of behavioral testing for locomotor activity, attention, and impulsivity. Although there is no obvious difference in gross development of offspring mice such as weight gain, high sucrose-exposed offspring mice showed a significantly increased locomotor activity. Moreover, these mice exhibited a dose-dependent decrease in attention and increase in impulsivity. In the striatum, a significantly increased dopamine transporter (DAT) mRNA expression was found in the Suc9 group along with dose-dependent decreases in the Drd1, Drd2 and Drd4 dopamine receptor subtypes. Furthermore, synaptosomal DAT protein expression was increased about twofold in the Suc9 group. Prenatal fructose exposure also induced hyperactive behavior in offspring mice suggesting the essential role of fructose in the dysregulated neurobehavioral development. These findings suggest prenatal sucrose consumption as a new risk factor for ADHD, which may need further attention and investigation in humans.

Keywords: ADHD; Behavior; Dopamine receptor; Dopamine transporter; Fructose; Sucrose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity / etiology*
  • Behavior, Animal
  • Diet
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / drug effects
  • Phenotype
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • RNA, Messenger / metabolism
  • Receptors, Dopamine
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D4 / metabolism
  • Risk Factors
  • Sucrose / adverse effects*

Substances

  • DRD2 protein, mouse
  • Dopamine Plasma Membrane Transport Proteins
  • Drd1 protein, mouse
  • Drd4 protein, mouse
  • RNA, Messenger
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • Sucrose