5'-Nucleotidase activity indicates sites of synaptic plasticity and reactive synaptogenesis in the human brain

The localization and morphological assessment of plastic or newly formed synapses in the human brain remains difficult due to the lack of specific markers. The ectoenzyme 5'-nucleotidase may represent a useful marker of these structures, since in adult rodents synaptic 5'-nucleotidase activity is restricted to sites of spontaneous synaptic turnover and induced reactive synaptogenesis. However, it is unclear to what extent synaptic 5'-nucleotidase activity occurs in the normal human brain, and whether reactive synaptogenesis, as seen e.g. in temporal lobe epilepsy (TLE), is associated with this ectoenzyme. Therefore, we have investigated the histochemical distribution of 5'-nucleotidase in hippocampal control specimens (n = 3) and in the hippocampus of TLE patients (n = 13). In controls, 5'-nucleotidase activity was present in the dentate gyrus molecular layer (DG-ML) and the mossy fiber termination field within the CA4 and CA3 subfields. Compared with controls, TLE specimens revealed markedly increased 5'-nucleotidase labeling in the DG-ML, implying TLE-associated reactive synaptogenesis in this hippocampal region. In contrast to GAP-43, synaptophysin, and dynorphin A, synaptic 5'-nucleotidase activity may serve as a potential specific indicator of plastic synapses or newly formed terminals in the human brain and prove useful for the study of diseases involving aberrant sprouting or altered synaptic plasticity.