sam-e causes brain damage?

eric errock at rcn.com
Sun Oct 8 20:08:29 EST 2000

ok, i stumbled accross the first one when reading a neurology discussion
I relize that the studies invovle SAM and not SAM-e, but again they are
linking the neural damage to elevated SAM and elevated methylation.
Also, im fairly sure that ive heard of people reporting parkinsons symptoms
from sam-e which im looking for evidence of on deja.

Email Address:

Mol Neurobiol 1994 Aug-Dec;9(1-3):149-61

Substantia nigra degeneration and tyrosine hydroxylase depletion caused by
excess S-adenosylmethionine in the rat brain. Support for an excess
methylation hypothesis for parkinsonism.

Charlton CG, Mack J
Department of Pharmacology, Meharry Medical College, Nashville, TN 37208.

The major symptoms of Parkinson's disease (PD) are tremors, hypokinesia,
rigidity, and abnormal posture, caused by degeneration of dopamine (DA)
neurons in the substantia nigra (SN) and deficiency of DA in the neostriatal
dopaminergic terminals. Norepinephrine, serotonin, and melanin pigments are
also decreased and cholinergic activity is increased. The cause of PD is
unknown. Increased methylation reactions may play a role in the etiology of
PD, because it has been observed recently that the CNS administration of
S-adenosyl-L-methionine (SAM), the methyl donor, caused tremors,
hypokinesia, and rigidity; symptoms that resemble those that occur in PD.
Furthermore, many of the biochemical changes seen in PD resemble changes
that could occur if SAM-dependent methylation reactions are increased in the
brain, and interestingly, L-DOPA, the most effective drug used to treat PD,
reacts avidly with SAM. So methylation may be important in PD; an idea that
is of particular interest because methylation reactions increase in aging,
the symptoms of PD are strikingly similar to the neurological and functional
changes seen in advanced aging, and PD is age-related. For methylation to be
regarded as important in PD it means that, along with its biochemical
reactions and behavioral effects, increased methylation should also cause
specific neuronal degeneration. To know this, the effects of an increase in
methylation in the brain were studied by injecting SAM into the lateral
ventricle of rats. The injection of SAM caused neuronal degeneration, noted
by a LOSS OF NEURONS, gliosis, and increased silver reactive fibers in the
SN. The degeneration was accompanied with a decrease in SN tyrosine
hydroxylase (TH) immunoreactivity, and degeneration of TH-containing fibers.
At the injection site in the lateral ventricle it appears that SAM caused a
weakening or dissolution of the intercellular substances; observed as a
disruption of the ependymal cell layer and the adjacent caudate tissues. SAM
may also cause BRAIN ATROPHY; evidenced by the dilation of the cerebral
ventricle. Most of the SAM-induced anatomical changes that were observed in
the rat model are similar to the changes that occur in PD, which further
support a role of SAM-dependent increased methylation in PD.

PMID: 7888091, UI: 95194587

and im sure weve all seen :::

  Charlton CG.  Crowell B Jr.
  Department of Physiology, Meharry Medical College, Nashville, TN 37208.
  Parkinson's disease-like effects of S-adenosyl-L-methionine: effects of
  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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