Publication: Physiology and pathophysiology of nitric oxide
in the nervous system, with special mention of
the islands of Calleja and the circunventricular organs
Authors
Rodrigo, J. ; Alonso, D. ; Bentura, M.L. ; Castro-Blanco, S. ; Encinas, J.M. ; Fernández, A.P. ; Fernández-Vizarra, P. ; Richart, A. ; Santacana, M. ; Serrano, J. ; Martínez, A.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Nitric oxide (NO) has been recognized as a
key regulatory factor in many physiological processes,
including central nervous system function, development,
and phatophysiology. NO is produced by a class of
enzymes known as NO synthases (NOS) and in normal
adult animals only the neuronal isoform (nNOS) is
detectable. During cortical development, nNOS was
found at E14 in neuroblasts of the marginal zone and its
expression raised to a zenith by P5, decreasing
afterwards until reaching a steady level by P10. At that
time, nNOS was found mainly in pyramidal neurons.
Interestingly, the inducible isoform of the enzyme
(iNOS) was also active from P3 to P7, but it disappeared
almost completely by P20. The neurodegeneration
observed during normal aging and following hypoxic
accidents seems to be the result of cumulative free
radical damage, and excessive production of NO may be
at the basis of the cascade. After ischemic events we
observed an elevation in the number of neurons
expressing nNOS coincident with an elevation in Ca2+-
dependent NOS activity for up to 120 min. After this
period, nNOS activity began to decrease but it was
substituted by a rapid increase in Ca2+-independent
activity coincident with the histological appearance of
previously undetectable iNOS-immunoreactive neurons.
These increases in NO production were accompanied by
specific patterns of protein nitration, a process that
seems to result in loss of protein function. In particular,
we observed a correlation between exposure to
ischemia-reperfusion and nitration of cytochrome c. This
process was coincident with the exit of the cytochrome
from the mitochondria to the surrounding cytoplasm, an
early event in neuronal apoptosis. Interestingly, most of
the morphological and molecular changes associated
with ischemic damage were prevented by treatment with
inhibitors of NO production, indicating a clear path in the search for efficacious drugs in the battle against
cerebrovascular accidents.
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