Methylazoxymethanol acetate does not fully block cell genesis in the young and aged dentate gyrus

Eur J Neurosci. 2005 Aug;22(3):778-83. doi: 10.1111/j.1460-9568.2005.04262.x.

Abstract

During adulthood, new neurons are continuously added to the mammalian dentate gyrus (DG). An increasing number of studies have correlated changes in rates of dentate neurogenesis with memory abilities. One study based on subchronic treatment with the toxin methylazoxymethanol acetate (MAM) has provided causal evidence that neurogenesis is involved in hippocampal-dependent trace conditioning. In contrast, spatial learning is not impaired following MAM treatment. We hypothesized that this was due to the small residual number of new cells produced following MAM treatment. In the present experiment, we attempted to achieve a higher level of reduction of adult-generated cells following MAM treatment in young and aged rats. We found only a partial reduction of adult-generated cells in the DG. More importantly, independently of the age of the animals, MAM treatment at a dose necessary to reduce neurogenesis altered the overall health of the animals. In conclusion, the behavioural results obtained following subchronic treatment with high doses of MAM in adulthood must be interpreted with extreme caution.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / physiology*
  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Body Weight / drug effects
  • Body Weight / physiology
  • Bromodeoxyuridine / metabolism
  • Cell Count / methods
  • Cell Proliferation / drug effects*
  • Dentate Gyrus / cytology*
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / metabolism
  • Dose-Response Relationship, Drug
  • Immunohistochemistry / methods
  • Ki-67 Antigen / metabolism
  • Male
  • Methylazoxymethanol Acetate / pharmacology*
  • Microtubule-Associated Proteins / metabolism
  • Motor Activity / drug effects
  • Neurons / drug effects*
  • Neurons / physiology
  • Neuropeptides / metabolism
  • Protein Synthesis Inhibitors / pharmacology*
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Time Factors

Substances

  • Ki-67 Antigen
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Protein Synthesis Inhibitors
  • doublecortin protein
  • Methylazoxymethanol Acetate
  • Bromodeoxyuridine