SYNAPTOPHYSIN GENE-EXPRESSION IN HUMAN BRAIN - A QUANTITATIVE IN-SITUHYBRIDIZATION AND IMMUNOCYTOCHEMICAL STUDY

Synaptophysin is a presynaptic vesicle protein. Its quantitative detec tion has become established as a molecular marker of synaptic density. We have studied synaptophysin messenger RNA in the neocortex, hippoca mpus 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. Synapt ophysin was also measured immunocytochemically in the hippocampus. The level of synaptophysin messenger RNA expression was uniform in all ne ocortical areas examined. Strong correlations were found for the amoun t of synaptophysin messenger RNA between individual regions and betwee n homologous areas in the two hemispheres. Synaptophysin messenger RNA declined with increasing age and prolonged post mortem interval. Syna ptophysin immunoreactivity also reduced with age, as well as with dura tion 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. Signifi cantly greater synaptophysin immunoreactivity was seen in the left tha n the right CA4 and CA1 regions. These data show that quantitative det ection 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 sugge st a possible asymmetry of hippocampal synaptophysin expression. The l evel of synaptophysin messenger RNA paralleled that of synaptophysin i mmunoreactivity, indicating that changes in gene expression contribute to variations in the latter observed in aging and other situations. D etection of synaptophysin messenger RNA broadens the range of methods by which synaptic protein gene products can be studied and used as mar kers of synaptic density and synaptic involvement during physiological and pathological processes in human brain.