A high fat diet in glutamate 3-/Y mice causes changes in behavior that resemble human intellectual disability

Jian Ming Li, Xianyu Li, Lawrence W.C. Chan, Ruinian Hu, Sijun Yang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

5 Citations (Scopus)

Abstract

Cognitive impairment in individuals with intellectual disability (ID) is characterized by developmental delay and deficits in language and memory. Ionotropic AMPA mediate the majority of excitatory synaptic transmission in the central nervous system and are essential for the induction and maintenances of long-term potentiation (LTP) and long-term depression (LTD), two cellular models of learning and memory underlie many the symptoms of ID. Clinical research has found obese male patients with GluA3 interrupted underlie the symptom of ID. We tested GluA3-/Y mice under high fat diet (HFD) stress on a series of behavioral paradigms associated with symptoms of ID: wild type mice showed significant levels of sociability, while GluA3-/Y mice did not. Wild type mice showed significant preference for social novelty, while GluA3-/Y mice did not. Normal scores on relevant control measures confirmed general health and physical abilities in both GluA3-/Y and wild type mice (WT), ruling out artifactual explanations for social deficits. GluA3-/Y mice also showed working spatial memory behavior impairment in Y-maze test and abnormal anxiety in open-field test, compared to wild-type littermate controls. GluA3-/Y mice had a significantly reduced spontaneous activities tested by elevated plus maze, display both low social approach and resistance to change in routine on the T-maze, consistent with an ID-like phenotype. These findings demonstrate that selective gene deletion of GluA3 receptor in male mice under oxidative stress induced phenotypic abnormalities related to ID-like symptoms.

Original languageEnglish
Article number114050
JournalPhysiology and Behavior
Volume259
DOIs
Publication statusPublished - 1 Feb 2023

Keywords

  • Glutamate receptor 3
  • Intellectual disability
  • Phenotypes

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience

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