No abstract

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.

No abstract

Rapid-scanning x-ray fluorescence (RS-XRF) is a synchrotron technology that maps multiple metals in tissues by employing unique hardware and software to increase scanning speed. RS-XRF was validated by mapping and quantifying iron, zinc and copper in brain slices from Parkinson's disease (PD) and unaffected subjects. Regions and structures in the brain were readily identified by their metal complement and each metal had a unique distribution. Many zinc-rich brain regions were low in iron and vice versa. The location and amount of iron in brain regions known to be affected in PD agreed with analyses using other methods. Sample preparation is simple and standard formalin-fixed autopsy slices are suitable. RS-XRF can simultaneously and non-destructively map and quantify multiple metals and holds great promise to reveal metal pathologies associated with PD and other neurodegenerative diseases as well as diseases of metal metabolism.

The relationship between astrocytes forming in the presence of dibutyryl cyclic AMP (dBcAMP) in culture and reactive astrocytes responding to a cerebral cortex stab wound was investigated. using computerized image analysis (Zeiss IBAS 1) and immunocytochemical staining. The diameters of the nuclei of astrocytes in primary cultures of newborn mouse neopallial cells were compared to those of the nuclei of normal and reactive astrocytes in histological sections of mouse cerebral cortex. We found that the nuclei of astrocytes that formed in the presence of dBcAMP in cultures are significantly larger than those of spontaneously occurring small stellate astrocytes in culture and of normal astrocytes of the cerebral cortex in vivo but corresponded more closely to the nuclei of reactive astrocytes in the area surrounding a stab wound in the cerebral cortex. Large stellate cells formed in the presence of dBcAMP had vimentin and an increase in GFP-containing intermediate filaments. Formation of reactive astrocytes in vivo is also asssociated with an increase in both vimentin and GFP-containing intermediate filaments.These observations indicate a closer relationship of astrocytes formed in the presence of dBcAMP in cultures to the reactive astrocytes in the cerebral cortex than to normal astrocytes. We propose, therefore, that the large stellate astrocytes that form in the presence of dBcAMP be referred to as reactive astrocytes in culture.