Morphological alterations of the reticular thalamic nucleus in Engrailed-2 knockout mice

J Anat. 2020 May;236(5):883-890. doi: 10.1111/joa.13150. Epub 2020 Jan 23.

Abstract

The reticular thalamic nucleus (Rt) is a sheet of neurons that surrounds the dorsal thalamus laterally, along its dorso-ventral and rostro-caudal axes. It consists of inhibitory neurons releasing gamma-aminobutyric acid (GABA). This nucleus participates in the circuitry between the thalamus and the cerebral cortex, and its impairment is associated with neuro-psychiatric disorders. In this study, we investigated the Rt anatomy of Engrailed-2 knockout mice (En2-/- ), a mouse model of autism spectrum disorder (ASD), using parvalbumin as an immunohistochemical marker. We compared 4- and 6-week-old wild type (WT) and En2-/- mice using various morphometric parameters: cell area, shape factor, circularity and cell density. Significant differences were present in 6-week-old male mice with different genetic background (WT vs. En2-/- ): the Rt neurons of En2-/- mice showed a bigger cell area, shape factor and circularity when compared with WT. Age (4 weeks vs. 6 weeks) influenced the shape factor of WT females, the circularity and cell density of En2-/- males, and the shape factor and circularity of En2-/- females. Gender affected cell density in 4-week-old WT mice, shape factor and cellularity of 6-week-old WT mice, and cell area, shape factor and cell density of En2-/- at 6 weeks. Intrasubject (left-right) asymmetry of Rt was never observed. These results show for the first time that sex- and age-related changes occur in the Rt GABAergic neurons of the En2-/- ASD mouse model.

Keywords: autism spectrum disorder; engrailed; gamma-aminobutyric acid; mouse; parvalbumin; reticular thalamic nucleus.

MeSH terms

  • Animals
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / metabolism
  • Disease Models, Animal
  • Female
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism*
  • Parvalbumins / metabolism
  • Sex Factors
  • Thalamic Nuclei / metabolism*

Substances

  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Parvalbumins
  • engrailed 2 protein