The neuropathological investigation of the brain in a monkey model of autism spectrum disorder with ABCA13 deletion

Int J Dev Neurosci. 2018 Dec:71:130-139. doi: 10.1016/j.ijdevneu.2018.09.002. Epub 2018 Sep 7.

Abstract

The precise biological etiology of autism spectrum disorder (ASD) remains unknown. In this study, we investigated the neuropathology of a monkey model of autism Human ABCA13 is the largest ABC transporter protein, with a length of 5058 amino acids and a predicted molecular weight of >450 kDa. However, the function of this protein remains to be elucidated. This protein is thought to be associated with major psychiatric disease. Using this monkey model of autism with an ABCA13 deletion and a mutation of 5HT2c, we neuropathologically investigated the changes in the neuronal formation in the frontal cortex. As a result, the neuronal formation in the cortex was found to be disorganized with regard to the neuronal size and laminal distribution in the ABCA13 deletion monkey. The catecholaminergic and GABAergic neuronal systems, serotoninergic neuronal formation (5HT2c) were also found to be impaired by an immunohistochemical evaluation. This study suggested that ABCA13 deficit induces the impairment of neuronal maturation or migration, and the function of the neuronal network. This protein might thus play a role in the neurodevelopmental function of the central nervous system and the dysfunction of this protein may be a pathophysiological cause of mental disorders including autism.

Keywords: ABCA13; Autism; Macaque; Neuropathology; Neurotransmitter.

MeSH terms

  • ATP-Binding Cassette Transporters / deficiency*
  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / pathology*
  • Brain / pathology*
  • Disease Models, Animal
  • Haplorhini
  • Nerve Tissue Proteins / metabolism
  • Neural Pathways / pathology*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuropeptide Y / metabolism
  • Neurotransmitter Agents / metabolism
  • Rats
  • Sequence Deletion

Substances

  • ABCA13 protein, human
  • ATP-Binding Cassette Transporters
  • Nerve Tissue Proteins
  • Neuropeptide Y
  • Neurotransmitter Agents