Effects of diethyldithiocarbamate (dedtc) throughout mouse brain development. Alterations in myelination process.
F. Junyent, T. Valente, L. Valente, L. Lima*,C. Auladell
Departament Biologia Cel•lular. Universitat de Barcelona. Diagonal 645 08028 Barcelona
*Laboratorio de Neuroquímica.Centro de Química.Instituto Venezolano de Investigaciones Científicas.Caracas,Venezuela
Different studies “in vivo” reported that the diethyldithiocarbamat (DEDTC) acts as a chelatable agent of endogenous biometals, with a high specificity for copper and zinc. In addition, has been determined that it can induce the inhibition of different enzymes, such as aldehyde deshydrogenase, dopamine beta hidroxylase, certain superoxide dismutase, and other enzymes.
Thus the effects of DEDTC would be similar to the ones determined by Cuprizone with a high chelatable specificity for copper and clearly identified with a demyelination process.
The aim of this work was an “in vivo” study of physiological, cellular and molecular effects of DEDTC in mice brain throughout development.
The animals were injected intraperitoneally by DEDTC daily, from P2 until P15. The animals were perfused at different postnatal days. From the dissected brains, coronal sections were obtained for histochemical and immunohistochemical techniques.
The treatment with DEDTC throughout postnatal development revealed important physiological alterations in the organism, such as a general growth delay. It’s important to mention the observed delay in the hair initial growth, and in the eyes opening after birth.
By different histochemical techniques (Nissl, Hematoxilin-eosin) a reduction in different brain areas was clearly observed. In addition, a higher density of cells was detected in specific areas, such as subventricular zone (svz), which is related with cell proliferation, together with alterations in the formation of cortical layers.
The immunohistochemical techniques supported those previous results. Therefore by the GFAP ( “Glial Fibrillar Acidic Protein”) antibody, a different pattern of astrocytes was observed, mainly in the cortical areas, together with a higher density of cells in specific zones, such as svz. Observations at high magnification, revealed that GFAP positive cells in treated animals displayed an altered morphology, not correlated with the characteristic migrating aspect detected in untreated animals.
The PCNA (“Proliferating Cell Nuclear Antigen”) antibody reported the existence of changes in rate proliferation, mainly appreciated at the svz where an increase in PCNA-IR cells was determined.
All these results suggested that the sequential DEDTC administration induces a physiological, cellular and molecular delay in development. Moreover, the alterations detected in the pattern and morphology of GFAP-IR cells, together with changes in the migration process, suggested that the myelination process would be affected.
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