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Peter M Wigmore

Publications and source records attributed to Peter M Wigmore.

4 recordsLinked to original sources

Treatment with olanzapine increases cell proliferation in the subventricular zone and prefrontal cortex.

The present study examines the effect of chronic treatment with two atypical neuroleptics, commonly used to treat schizophrenia. Adult rats were given either risperidone or olanzapine in their drinking water for 21 days. Memory was assessed on the first and last day of treatment using an object discrimination test, and the rate of cell proliferation in the subventricular zone (SVZ), dentate gyrus (DG) and prefrontal cortex (PFC) was quantified by immuno staining for Ki-67. The results show that both risperidone and olanzapine significantly improved performance in object discrimination after 21 days, and additionally, olanzapine significantly increased cell proliferation in the SVZ and PFC but not the DG.

Animals↗

Novel strategy to study gene expression and function in developing cerebellar granule cells.

The advent of techniques for global analyses of cell biology, such as genomics and proteomics, opens the way to rapid progress in understanding the molecular control of developing tissues. However, such studies in the CNS are hindered by the complexity of this tissue. In particular, few approaches allow cells to be isolated that are enriched for specific stages of their maturation. We describe a new strategy to study gene expression and function in cerebellar granule cells. In these experiments, we have used square pulse electroporation to introduce fluorescent dye or DNA constructs into immature granule cell precursors in situ. This method only labels granule cell precursors in the superficial part of the external granule layer. Combining this labelling with fluorescent activated cell sorting (FACS) allows the transfected cells to be isolated at any time during their subsequent development, thus providing a means of analysing granule cells as they undergo maturation. This transfection method can be used to study events in the normal maturation of granule cells or the effects of introduced transgenes. Such studies can be carried out on cells purified from primary cultures or cells in situ using cerebellar slice cultures. Our strategy provides a new route to detailed analysis of the role of genes in controlling many aspects of granule cell biology. These approaches will allow recent global analyses to be more readily applied to subpopulations of cells in complex tissues.

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Gene transfer into intact fetal skeletal muscle grown in vitro.

The development of an organ culture system for growing prenatal intercostal muscle in vitro and its use to study gene function is described. Fetal skeletal muscle is relatively inaccessible during the key stages of its development, and this method enables DNA transfections and other manipulations to be carried out. The system allows cell proliferation and differentiation to continue and also maintains the morphology and fiber types of developing muscle. Gene transfer into cultured embryonic intercostal muscle was achieved by square-pulse electroporation of intact pieces of tissue. Expression of a marker gene (GFP) was found within 5 h and maintained for 2 days in muscle fibers and cells. The technique should enable the function of genes implicated in muscle development and disease to be studied at stages when access is difficult and in a controlled environment.

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Molecular and cellular mechanisms involved in the generation of fiber diversity during myogenesis.

Skeletal muscles have a characteristic proportion and distribution of fiber types, a pattern which is set up early in development. It is becoming clear that different mechanisms produce this pattern during early and late stages of myogenesis. In addition, there are significant differences between the formation of muscles in head and those found in rest of the body. Early fiber type differentiation is dependent upon an interplay between patterning systems which include the Wnt and Hox gene families and different myoblast populations. During later stages, innervation, hormones, and functional demand increasingly act to determine fiber type, but individual muscles still retain an intrinsic commitment to form particular fiber types. Head muscle is the only muscle not derived from the somites and follows a different development pathway which leads to the formation of particular fiber types not found elsewhere. This review discusses the formation of fiber types in both head and other muscles using results from both chick and mammalian systems.

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