Doublecortin expression in the normal and epileptic adult human brain

Eur J Neurosci. 2008 Dec;28(11):2254-65. doi: 10.1111/j.1460-9568.2008.06518.x.

Abstract

Mesial temporal lobe epilepsy (MTLE) is a neurological disorder associated with spontaneous recurrent complex partial seizures and hippocampal sclerosis. Although increased hippocampal neurogenesis has been reported in animal models of MTLE, increased neurogenesis has not been reported in the hippocampus of adult human MTLE cases. Here we showed that cells expressing doublecortin (Dcx), a microtubule-associated protein expressed in migrating neuroblasts, were present in the hippocampus and temporal cortex of the normal and MTLE adult human brain. In particular, increased numbers of Dcx-positive cells were observed in the epileptic compared with the normal temporal cortex. Importantly, 56% of Dcx-expressing cells in the epileptic temporal cortex coexpressed both the proliferative cell marker, proliferating cell nuclear antigen and early neuronal marker, TuJ1, suggesting that they may be newly generated neurons. A subpopulation of Dcx-positive cells in the epileptic temporal cortex also coexpressed the mature neuronal marker, NeuN, suggesting that epilepsy may promote the generation of new neurons in the temporal cortex. This study has identified, for the first time, a novel population of Dcx-positive cells in the adult human temporal cortex that can be upregulated by epilepsy and thus, raises the possibility that these cells may have functional significance in the pathophysiology of epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Cell Movement / physiology
  • Cell Proliferation
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Epilepsy, Temporal Lobe / metabolism*
  • Epilepsy, Temporal Lobe / pathology
  • Epilepsy, Temporal Lobe / physiopathology
  • Female
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Humans
  • Immunohistochemistry
  • Male
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Neurogenesis / physiology*
  • Neuronal Plasticity / physiology
  • Neurons / metabolism*
  • Neuropeptides / metabolism*
  • Proliferating Cell Nuclear Antigen / analysis
  • Proliferating Cell Nuclear Antigen / metabolism
  • Recovery of Function / physiology
  • Regeneration / physiology
  • Stem Cells / metabolism*
  • Tubulin / analysis
  • Tubulin / metabolism
  • Up-Regulation / physiology
  • Young Adult

Substances

  • Biomarkers
  • DCX protein, human
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Proliferating Cell Nuclear Antigen
  • TUBB3 protein, human
  • Tubulin