Kirsty Greenwood

Kir4.1 expression by astrocytes and oligodendrocytes in CNS white matter: a developmental study in the rat optic nerve

Deletion studies in transgenic mice indicate that the potassium inward rectifying channel Kir4.1 is crucial for oligodendrocyte differentiation and has a special role in regulation of extracellular potassium (K+), a major function of astrocytes. However, there are conflicting reports on whether Kir4.1 is expressed by white matter astrocytes and oligodendrocytes, raising doubts over its functions. Here, we have examined Kir4.1 expression in astrocytes and oligodendrocytes of the rat optic nerve, a typical central nervous system white matter tract. Single and double immunofluorescence labelling was performed on frozen sections from optic nerves aged postnatal day (P)5, 10, 15, 20 and adult, using anti‐Kir4.1 antibodies and the glia‐specific antibodies glial fibrillary acidic protein (GFAP, astrocytes), carbonic anhydrase II (CAII, oligodendrocyte somata and processes) and myelin basic protein (MBP, oligodendrocyte myelin sheaths). The results demonstrate Kir4.1 expression in rows of glial cells as early as P5, and this pattern persisted throughout development and into adulthood, consistent with early expression of Kir4.1 on developing oligodendrocytes. Clear co‐expression of Kir4.1 and GFAP is first evident at P10 and increases to adult levels by P15 and P20, which correlates with the development of K+ regulation between P15 and P20. Astrocyte expression of Kir4.1 is localized to perivascular end‐feet and fine processes within the fascicles of myelinated axons, consistent with a role in K+ spatial buffering between nodes of Ranvier and blood vessels. By contrast, Kir4.1 is concentrated in the cell bodies of oligodendrocytes, and there is no apparent co‐expression with MBP+ myelin sheaths, suggesting oligodendroglial Kir4.1 channels are not involved in K+ regulation. The results support roles for Kir4.1 in both oligodendrocyte differentiation and K+ regulation by astrocytes.

The functional outcome of executive impairments in the Psychomotor Poverty syndrome: Verbal working memory may mediate the relationship between memory and real-life skills

This study investigated whether executive impairments are predictive of the poor functional outcome found in the Psychomotor Poverty syndrome of schizophrenia. Functional impairments in a supermarket-shopping task were investigated in a cross-sectional study of three groups of participants: those with and those without psychomotor poverty symptoms and normal controls. Groups were matched for age, sex, premorbid IQ and memory function. Novel measures of real-life skills were developed which emphasised relevant executive processes within the shopping task. Four executive tasks were also administered which provided six measures of working memory, initiation and strategy use. The psychomotor poverty group demonstrated verbal working memory, spatial strategy and verbal initiation impairments and greater impairment in functional accuracy and strategic efficiency on the shopping task compared to the non-psychomotor poverty group and normal controls. The nonpsychomotor poverty group were more efficient than controls in some real-life skills. Verbal working memory independently predicted functional accuracy and efficiency in relation to other executive processes. Neither verbal working memory nor general memory independently predicted accuracy or the majority of efficiency measures. Experimentally determined executive impairments are ecologically valid in their impact on functional outcome in schizophrenia. Verbal working memory may constitute an important mediator of the relationship between poor verbal memory and poor functional outcome in the psychomotor poverty syndrome. These findings provide a theoretical framework through which cognitive remediation programmes may be developed to enhance generalisable executive and real-life skills and improve the poor functional outcome in the psychomotor poverty syndrome of schizophrenia.