Degeneration of monoaminergic fibers in the aged micrencephalic rat

Neurosci Lett. 2005 Sep 2;385(1):82-6. doi: 10.1016/j.neulet.2005.05.020.


Age-related changes in the monoaminergic neuron systems in the brains of methylazoxymethanol acetate (MAM)-induced micrencephalic rats were studied. Neurochemical analysis revealed high levels of serotonin, norepinephrine and associated metabolites in several brain areas of MAM-treated rats. In particular, serotonin levels in the frontal cortex, cingulate cortex and hippocampus of 12-month-old (12 M) MAM-treated rats were significantly higher than in corresponding age-matched controls. Immunohistochemical analysis demonstrated numerous aberrant serotonin-immunoreactive fibers and small numbers of aberrant tyrosine hydroxylase-immunoreactive fibers in the septum, caudate putamen, thalamus, cerebral cortex, hippocampus and midbrain tegmentum of 12 M MAM-treated rats. Aberrant monoaminergic fibers characterized by swollen varicosities and thickening of intervaricose segments were common compared to 12 M control rats. In the cortex and hippocampus of 12 M MAM-treated rats, aberrant fibers were observed near cortical heterotopic tissue. These results indicate early onset of age-related degeneration of monoaminergic fibers in micrencephalic rats. Aged MAM-treated rats may thus offer a good model for studying age-related monoaminergic changes in the cortical heterotopic tissue of human cortical malformations.

Publication types

  • Comparative Study

MeSH terms

  • Aging / metabolism*
  • Animals
  • Biogenic Monoamines / metabolism*
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology*
  • Brain Injuries / chemically induced
  • Brain Injuries / complications
  • Brain Injuries / pathology
  • Chromatography, High Pressure Liquid / methods
  • Female
  • Immunohistochemistry / methods
  • Male
  • Methylazoxymethanol Acetate
  • Nerve Degeneration / etiology
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology
  • Nerve Fibers / metabolism*
  • Nerve Fibers / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors


  • Biogenic Monoamines
  • Methylazoxymethanol Acetate