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(Perhaps some of you missed this posting which contradicts
everything we have always been told, but apparently is
valid  --    nina)
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Chronic LD not toxic, may promote neural recovery
Date: 1/19/99

Chronic levodopa is not toxic for remaining dopamine
neurons, but instead
promotes their recovery, in rats with moderate nigrostriatal
lesions

MG Murer, G Dziewczapolski, LB Menalled, MC Garcia, Y Agid,
O Gershanik, R
Raisman-Vozari

Annals of Neurology, 1998, Vol 43, Iss 5, pp 561-575

Six months of oral l-dopa caused no excess loss of
dopaminergic neurons
versus untreated controls, and may have promoted recovery of
surviving
neurons, according to this study on OHDA-lesioned rats. Rats
were
unilaterally injected with either saline or one of two
quantities of OHDA
(to produce moderate vs. severe lesions). Members of each
group were
randomly assigned to receive either vehicle or oral l-dopa.
Neuronal
survival was quantified by immunoautoradiography of tyrosine
hydroxylase,
vesicular monoamine transporter, and dopamine transporter.

Results showed:
a) L-dopa treatment caused no loss of dopaminergic neurons
in either
sham-lesioned or OHDA-lesioned rats compared to
sham-lesioned,
non-treated controls
b) L-dopa treatment caused no reduction in terminal axonal
arborization
c) In the moderately lesioned group, treated rats showed,
"in the
denervated regions of the striatum, significantly higher
levels of the
three dopaminergic markers than their corresponding
vehicle-treated
control group, and also an increased density of
TH-immunoreactive
fibers."

The authors suggest the recovery is likely to be due to
axonal sprouting of
surviving dopaminergic neurons. They also note that their
study provided no
evidence of accompanying functional recovery in this
subgroup. In discussing
the relevance of these findings to human PD
patients, they state "our results cannot be considered as
definitive
evidence of an absence of toxicity of chronic levodopa in PD
patients" but
note that other recent findings support the absence of
l-dopa toxicity as
well.

An editorial by Stanley Fahn accompanies the article.


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