Alterations of neuronal precursor cells in stages of human adult neurogenesis in heroin addicts

Drug Alcohol Depend. 2015 Nov 1:156:139-149. doi: 10.1016/j.drugalcdep.2015.09.005. Epub 2015 Sep 15.

Abstract

Background: Adult neurogenesis has been shown to occur throughout life and different brain pathologies were demonstrated to be associated with altered neurogenesis. Here, an impact of heroin addiction on neurogenesis in humans is hypothesised.

Methods: Post mortem hippocampal specimens of drug addicts with known heroin abuse and a group of non-addictive control subjects were analysed, using antibodies indicating different stages of neurogenesis. The subgranular zone of the dentate gyrus was examined qualitatively and quantitatively.

Results: The data indicate (i) a decreased number of neural precursor cells, (ii) accompanied by low rates of proliferation and (iii) a marked loss of dendritic trees in targeting cells in heroin fatalities. (iv) The age-dependent increase of differentiating cells in the healthy controls was not observed in the addicts. Additionally, double immunofluorescence labelling indicated the precursor nature of Musashi-1 positive cells in the human subgranular zone of the dentate gyrus.

Conclusions: Present data firstly demonstrate the influence of drug addiction with known heroin abuse on different developmental stages of progenitors in the dentate gyrus. The patterns of antibody staining suggest a distinct inhibition of neurogenesis at the stage of neural precursor cells and revealed morphological changes in targeting cells in cases of heroin addicts as compared to healthy controls. These alterations could be considerable for memory and cognitive deficits as well as addictive behaviour in chronic drug abusers and may give rise to specific pro-neurogenic therapies.

Keywords: Drug abuse; Heroin; Hippocampus; Human; Neural precursor cell; Neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autopsy
  • Case-Control Studies
  • Cell Differentiation
  • Cognition Disorders
  • Dentate Gyrus / metabolism
  • Dentate Gyrus / pathology*
  • Female
  • Fluorescent Antibody Technique
  • Heroin Dependence / metabolism
  • Heroin Dependence / pathology*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Male
  • Middle Aged
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology*
  • Neurogenesis*
  • Neurons / metabolism
  • Neurons / pathology*
  • Young Adult