Development of rat oligodendrocyte precursor cells

Differential effects of antipsychotics on the development of rat oligodendrocyte precursor cells exposed to cuprizone
 
Abstract
Cuprizone (CPZ) is a copper-chelating agent and has been shown to induce white matter damage in mice and rats. The compromised white matter and oligodendrocytes (OLs) respond to some antipsychotics in vivo. However, little is known about the effects of antipsychotics on cultured OLs in the presence of CPZ. The aim of this study was to examine effects of some antipsychotics on developing OLs in the presence of CPZ. Oligodendrocyte progenitor cells (OPCs) were prepared from rat embryos; OLs at different developing stages were labeled with specific antibodies; levels of CNP and MBP proteins in mature OLs wereshow more contentThe CPZ-fed mice showed poor motor coordination in a rota-rod analysis [14] and a murine motor test [22]. In the 3rd and 4th weeks after consuming CPZ-containing diet, mice exhibited an increase in CNS activity. Moreover, mice displayed prepulse inhibition deficits during the 2nd and 3rd weeks of CPZ exposure period and showed less social interaction after CPZ exposure for 46 weeks [25, 44]. The CPZ-fed mice also showed spatial working memory impairment [25, 39, 44]. CPZ-induced demyelination and behavioral changes were also seen in rats [16, 18, 34]. These previous studies reminded us of an emerging hypothesis that oligodendroglial dysfunction and even death, with subsequent abnormalities in myelin maintenance and repair, contribute to the schizophrenic syndrome [10].
In efforts to test the OL deficit hypothesis of schizophrenia, we examined the effects of some existing antipsychotic drugs on the CPZ-induced white matter damage and behavioral changes in C57BL/6 mice. We found that the CPZ-induced demyelination and myelin breakdown as well as the concurrent neuropathological changes in the mice were ameliorated by the antipsychotic quetiapine [QUE; 41, 50]. But, the other antipsychotics (clozapine, CLZ and haloperidol, HAL) showed different effects on the CPZ-induced changes [42]. Also, these antipsychotic drugs differentially affected the recovery of CPZ-induced changes after removal ofGet Access
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