sam can induce Parkinson's symptoms

From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Thu Nov 04 1999 - 06:17:31 MST


Authors
  Charlton CG. Crowell B Jr.
Institution
  Department of Physiology, Meharry Medical College, Nashville, TN 37208.
Title
  Parkinson's disease-like effects of S-adenosyl-L-methionine: effects of
  L-dopa.
Source
  Pharmacology, Biochemistry & Behavior. 43(2):423-31, 1992 Oct.
Abstract
  The major symptoms of Parkinson's disease (PD) are due to degeneration of the
  nigrostriatal pathway and depletion of dopamine (DA). Tyrosine hydroxylase
  (TH), norepinephrine (NE), serotonin (5-HT), and melanin pigments are also
  decreased and acetylcholinergic activity increased. Biochemically, increased
  methylation can cause the depletion of DA, NE, 5-HT, and melanin pigments and
  also an increase of acetylcholine; thus, increased methylation can present a
  biochemical picture that resembles the biochemical changes that occur in PD.
  During the therapy of PD with L-dopa, it is well known that L-dopa reacts
  avidly with S-adenosyl-L-methionine (SAM), the biologic methyl donor, to
  produce 3-O-methyl-dopa. Correspondingly, L-dopa has been shown to deplete
  the concentration of SAM, and SAM has been found to induce PD-like motor
  impairments in rodents; therefore, an excess of SAM-dependent methylation may
  be associated with Parkinsonism. To further study the effects of methylation,
  SAM was injected into the lateral ventricle of rats. SAM caused tremors,
  rigidity, abnormal posture, and dose-related hypokinesia. Doses of 9.38, 50,
  and 400 nM/rat caused 61.9, 73.4, and 94.8% reduction, respectively, of motor
  activity. A 200-mg/kg IP dose of L-dopa, given before 50 nM SAM, blocked the
  SAM-induced hypokinesia. SAM also caused a decrease in TH immunoreactivity,
  apparent degeneration of TH-containing fibers, loss of neurons, and the
  accumulation of phagocytic cells in the substantia nigra. These results
  showed that excess SAM in the brain, probably due to its ability to increase
  methylation, can induce symptoms that resemble some of the changes that occur
  in PD.



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