Another therapy for hexachlorophene's effects on the mitochondria of oligodendrocytes?

In the last entry I cited Lamictal's and topamax's therapeutic value. Here is how Seraquel/Quetiapine also might be able to address damages to oligodendrocytes by mitochondrial genetics or a mitochondrial neurotoxin. There are a number of research articles on cuprizone. The effectiveness of the mitochondrial cuprizone model in mice correlates with the hexachlorophene model in rats. Shouldn't both of their damages to oligodendrocytes be addressed by Seroquel/Quetiapine?

The second article addresses glucocorticoids and oligodendrocytes. This may also explain a reason that the cortisol-lowering Seroquel affects important changes to the oligodendrocytes.

Mol Psychiatry. 2007 Aug 7. [Epub ahead of print]

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Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes.

Xiao L, Xu H, Zhang Y, Wei Z, He J, Jiang W, Li X, Dyck LE, Devon RM, Deng Y, Li XM.

1Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, SK, Canada.

Recent neuroimaging and postmortem studies have reported abnormalities in white matter of schizophrenic brains, suggesting the involvement of oligodendrocytes in the etiopathology of schizophrenia. This view is being supported by gene microarray studies showing the downregulation of genes related to oligodendrocyte function and myelination in schizophrenic brain compared to control subjects. However, there is currently little information available on the response of oligodendrocytes to antipsychotic drugs (APDs), which could be invaluable for corroborating the oligodendrocyte hypothesis. In this study we found: (1) quetiapine (QUE, an atypical APD) treatment in conjunction with addition of growth factors increased the proliferation of neural progenitors isolated from the cerebral cortex of embryonic rats; (2) QUE directed the differentiation of neural progenitors to oligodendrocyte lineage through extracellular signal-related kinases; (3) addition of QUE increased the synthesis of myelin basic protein and facilitated myelination in rat embryonic cortical aggregate cultures; (4) chronic administration of QUE to C57BL/6 mice prevented cortical demyelination and concomitant spatial working memory impairment induced by cuprizone, a neurotoxin. These findings suggest a new neural mechanism of antipsychotic action of QUE, and help to establish a role for oligodendrocytes in the etiopathology and treatment of schizophrenia.Molecular Psychiatry advance online publication, 7 August 2007; doi:10.1038/sj.mp.4002064.

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HERE IS THE CORTICOSTERONE -OLIGODENDROCYTE LINK THAT SEEMS TO GIVE ONE WAY FOR QUETIAPINE TO HAVE AN EFFECT THAT COUNTERS THE EARLIER HEXACHOROPHENE- OLIGODENDROCYTE TOXICITY.

GLIA 31:219-231, 2000.

Prolonged corticosterone treatment of adult rats inhibits the proliferation of oligodendrocyte progenitors present throughout white and gray matter regions of the brain

Gérard Alonso *
CNRS-UMR5101, CCIPE, Montpellier Cedex 05, France
email: Gérard Alonso (alonso@bacchus.montp.inserm.fr)
*Correspondence to Gérard Alonso, CNRS-UMR5101. CCIPE, 141 rue de la Cardonille, 34094 Montpellier Cedex 05, France
setDOI("ADOI=10.1002/1098-1136(200009)31:33.0.CO;2-R")
Keywords
glucocorticoids; astrocytes; microglia; germinative zones; remyelination
Abstract
It is well established that glucocorticoids inhibit the proliferation of progenitor cells that occurs in the hippocampal dentate gyrus of adult mammals. Active cell proliferation also occurs in the subventricular zone (SVZ) of the lateral ventricle and, to a lesser extent, throughout white and gray matter regions of the adult brain. The aim of the present study was to determine whether extrahippocampal cell proliferation is also affected by glucocorticoids. The cell proliferation marker bromodeoxyuridine (BrdU) was administered to control rats, to adrenalectomized rats, and to rats treated with a daily injection of corticosterone (10 mg/kg) for a period of 15 days. In control and adrenalectomized rats, high to low numerical densities of BrdU-labeled nuclei were detected within the different forebrain regions examined. In rats treated with corticosterone, a dramatic decrease of cell proliferation was detected in the dentate gyrus, but also throughout all white and gray matter regions examined, except for the SVZ of the lateral ventricle. Double-labeling experiments indicated that throughout the different white and gray forebrain regions examined, except for the SVZ, BrdU-labeled nuclei were essentially associated with cells immunostained for the marker of oligodendrocyte progenitors NG2. These data indicate that glucocorticoids inhibit the proliferation of oligodendrocyte precursors located throughout the white and gray matter regions of the adult rat brain. Since the proliferation of oligodendrocyte precursors plays a major role in the processes of remyelination, these data raise the question of possible detrimental effects of therapeutic treatments of CNS trauma based on the administration of glucocorticoids. GLIA 31:219-231, 2000. © 2000 Wiley-