Spared cognitive and behavioral functions prior to epilepsy onset in a rat model of subcortical band heterotopia

Brain Res. 2019 May 15:1711:146-155. doi: 10.1016/j.brainres.2019.01.030. Epub 2019 Jan 25.

Abstract

Subcortical band heterotopia (SBH), also known as doublecortex syndrome, is a malformation of cortical development resulting from mutations in the doublecortin gene (DCX). It is characterized by a lack of migration of cortical neurons that accumulate in the white matter forming a heterotopic band. Patients with SBH may present mild to moderate intellectual disability as well as epilepsy. The SBH condition can be modeled in rats by in utero knockdown (KD) of Dcx. The affected cells form an SBH reminiscent of that observed in human patients and the animals develop a chronic epileptic condition in adulthood. Here, we investigated if the presence of a SBH is sufficient to induce cognitive impairment in juvenile Dcx-KD rats, before the onset of epilepsy. Using a wide range of behavioral tests, we found that the presence of SBH did not appear to affect motor control or somatosensory processing. In addition, cognitive abilities such as learning, short-term and long-term memory, were normal in pre-epileptic Dcx-KD rats. We suggest that the SBH presence is not sufficient to impair these behavioral functions.

Keywords: Cognition; Cortex development; Cortical malformation; Doublecortin; Memory; Somatosensory processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics
  • Asymptomatic Diseases
  • Behavior, Animal*
  • Cell Movement
  • Classical Lissencephalies and Subcortical Band Heterotopias / complications
  • Classical Lissencephalies and Subcortical Band Heterotopias / embryology
  • Classical Lissencephalies and Subcortical Band Heterotopias / genetics
  • Classical Lissencephalies and Subcortical Band Heterotopias / psychology*
  • Cognition*
  • Disease Models, Animal*
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Electroporation
  • Epilepsy / genetics*
  • Exploratory Behavior
  • Gray Matter / abnormalities
  • Gray Matter / embryology
  • Intellectual Disability / genetics*
  • Learning
  • Maze Learning
  • Memory
  • Microtubule-Associated Proteins / deficiency
  • Microtubule-Associated Proteins / genetics
  • Mosaicism
  • Neuropeptides / deficiency
  • Neuropeptides / genetics
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / toxicity
  • Rats
  • Rotarod Performance Test
  • Sensation
  • White Matter / abnormalities
  • White Matter / embryology

Substances

  • DCX protein, human
  • Dcx protein, rat
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Neuropeptides
  • RNA, Small Interfering