Biomedical subjects
K M Wets
Publications and source records attributed to K M Wets.
Neuronal and glial cell biology molecular clocks.
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Immunoidentification of cellular brain proteins associated with cognitive recovery in brain transplants.
In adult, lesion-impaired rat brain receiving embryonic day 15 (E15) fetal transplants, the level of expression of glial fibrillary acidic protein (GFAP) correlates positively with choline acetyltransferase (ChAT) levels and also with measurements of successful behavioural recovery. These results suggest that glial cells may play a pivotal role in the cognitive success of so-called cholinergic-rich transplants. The objective of this study was to investigate the association between GFAP- and ChAT-staining antigens in or around cholinergic-rich fetal grafts transplanted in adult cortex. An immunohistochemical fluorescent double-labelling technique was used to simultaneously identify GFAP- and ChAT-staining cells to assess whether there was a different type or distribution of cells present in these successful transplants. On brain sections of transplant area, GFAP-staining glial cells did not co-label with ChAT-staining cells. The transplant area, therefore, did not reveal a different type of cell from those seen in comparable normal cortical brain but rather a greater concentration of both GFAP- and ChAT-positive staining cells.
Specific brain protein changes correlated with behaviourally effective brain transplants.
The objective of this study was to identify cellular proteins that are associated with foetal brain transplants effective in reinstating memory function in adult rats with brain lesions. Quantitative memory deficits can be created in rats by lesioning the cholinergic projection system, using ibotenic acid. Previous work suggested that injection of cell suspensions prepared from presumptive cholinergic cells of foetal basal forebrain into adult brain, after such lesions, are most effective in restoring cognitive function. It was not clear, however, whether it was the cholinergic nature of the transplants that was critical for their success or whether other factors were involved. In this study, the proteins present in transplanted tissues and control brains were analysed by two-dimensional polyacrylamide gel electrophoresis to identify markers for the cells that were specifically correlated with restoration of cognitive function. On each gel, the relative optical densities of the same 33 selected proteins were measured on an interactive computerised image analyser. The amount of each protein was compared between treatment groups and correlated with four behavioural measurements. Seven of the proteins analysed had levels of expression that were either related to transplantation or correlated with behavioural performance. The proteins of interest were divided into the following three groups: (1) transplant-related proteins, (2) cholinergic transplant-specific proteins, and (3) behaviour-related proteins. Notable among the proteins of interest was one of the cholinergic transplant-specific proteins that was positively correlated with three of the four behavioural measurements and was also the only protein among those analysed that was significantly correlated with choline acetyltransferase (ChAT) levels. This has been identified, by immunoblotting, as glial fibrillary acidic protein, an astrocytic cell marker. These results suggest, therefore, that at least two cell types, astrocytes and ChAT(+)-staining cells, play an important role in the successful recovery of cognitive function. This study also identified possible protein markers for cognitive performance. The level of expression of two of the proteins analysed was not affected by lesioning or transplantation, but was significantly correlated with behaviour. One of these proteins, whose amounts correlated negatively with behavioural measurements, has been identified as neurone-specific enolase, a brain-specific neuronal cell marker.
Recent advances in drug delivery technology for neurology.
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