Reduced Glutamate Release in Adult BTBR Mouse Model of Autism Spectrum Disorder

Neurochem Res. 2016 Nov;41(11):3129-3137. doi: 10.1007/s11064-016-2035-5. Epub 2016 Aug 19.

Abstract

Autism spectrum disorder (ASD) is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. The BTBR T + Itpr3 tf (BTBR) mice have emerged as a well characterized and widely used mouse model of a range of ASD-like phenotype, showing deficiencies in social behaviors and unusual ultrasonic vocalizations as well as increased repetitive self-grooming. However, the inherited neurobiological changes that lead to ASD-like behaviors in these mice are incompletely known and still under active investigation. The aim of this study was to further evaluate the structure and neurotransmitter release of the glutamatergic synapse in BTBR mice. C57BL/6J (B6) mice were used as a control strain because of their high level of sociability. The important results showed that the evoked glutamate release in the cerebral cortex of BTBR mice was significantly lower than in B6 mice. And the level of vesicle docking-related protein Syntaxin-1A was reduced in BTBR mice. However, no significant changes were observed in the number of glutamatergic synapse, level of synaptic proteins, density of dendritic spine and postsynaptic density between BTBR mice and B6 mice. Overall, our results suggest that abnormal vesicular glutamate activity may underlie the ASD relevant pathology in the BTBR mice.

Keywords: Autism spectrum disorder; BTBR; Glutamate release; Glutamatergic synapse; Sociability.

MeSH terms

  • Animals
  • Autistic Disorder / metabolism*
  • Autistic Disorder / physiopathology
  • Behavior, Animal / physiology*
  • Dendritic Spines / metabolism*
  • Disease Models, Animal
  • Glutamic Acid / metabolism
  • Mice
  • Social Behavior*
  • Synaptic Transmission / physiology*

Substances

  • Glutamic Acid