Mice with reduced glutamate transporter GLT1 expression exhibit behaviors related to attention-deficit/hyperactivity disorder

• DOI: 10.1016/j.bbrc.2021.06.057
• Publication Date: 2021-06-21T09:25:58Z
• Authors: Yuichi Hiraoka; Kaori Sugiyama; Daiki Nagaoka; Iku Tsutsui-Kimura; Kenji F. Tanaka; Kohichi Tanaka
• Keywords: Male; Mice, Knockout; 0301 basic medicine; Mice; 03 medical and health sciences; Excitatory Amino Acid Transporter 2; Attention Deficit Disorder with Hyperactivity; Animals; Down-Regulation; Synaptic Transmission

Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder in children. Although animal models and human brain imaging studies indicate a significant role for glutamatergic dysfunction in ADHD, there is no direct evidence that glutamatergic dysfunction is sufficient to induce ADHD-like symptoms. The glial glutamate transporter GLT1 plays a critical role in glutamatergic neurotransmission. We report here the generation of mice expressing only 20% of normal levels of the GLT1. Unlike conventional GLT1 knockout mice, these mice survive to adulthood and exhibit ADHD-like phenotypes, including hyperactivity, impulsivity and impaired memory. These findings indicate that glutamatergic dysfunction due to GLT1 deficiency, a mechanism distinct from the dopaminergic deficit hypothesis of ADHD, underlies ADHD-like symptoms.