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.