Synaptophysin gene expression in human brain: a quantitative in situ hybridization and immunocytochemical study

Synaptophysin is a presynaptic vesicle protein. Its quantitative detection has become established as a molecular marker of synaptic density. We have studied synaptophysin messenger RNA in the neocortex, hippocampus and cerebellum using in situ hybridization histochemistry to see if the encoding transcript can be detected in post mortem human brain and to investigate factors which might influence its abundance. Synaptophysin was also measured immunocytochemically in the hippocampus. The level of synaptophysin messenger RNA expression was uniform in all neocortical areas examined. Strong correlations were found for the amount of synaptophysin messenger RNA between individual regions and between homologous areas in the two hemispheres. Synaptophysin messenger RNA declined with increasing age and prolonged post mortem interval. Synaptophysin immunoreactivity also reduced with age, as well as with duration of formalin fixation but not post mortem interval. Synaptophysin immunoreactivity correlated with the abundance of the messenger RNA in neurons within, and projecting to, each hippocampal subfield. Significantly greater synaptophysin immunoreactivity was seen in the left than the right CA4 and CA1 regions. These data show that quantitative detection of synaptophysin messenger RNA as well as synaptophysin itself can reliably be carried out in post mortem human brain sections. They are in keeping with other findings that synaptic density is relatively uniform through the neocortex and decreases with age. They also suggest a possible asymmetry of hippocampal synaptophysin expression. The level of synaptophysin messenger RNA paralleled that of synaptophysin immunoreactivity, indicating that changes in gene expression contribute to variations in the latter observed in aging and other situations. Detection of synaptophysin messenger RNA broadens the range of methods by which synaptic protein gene products can be studied and used as markers of synaptic density and synaptic involvement during physiological and pathological processes in human brain.