Immunohistochemical localization of GDNF in the human hippocampal formation from prenatal life to adulthood

Abstract

In this study, we examined the immunohistochemical occurrence and distribution of glial cell line-derived neurotrophic factor (GDNF) in autoptic specimens of normal human hippocampus at different ages, from 22 weeks of gestation (w.g.) to adult life. Two different anti-GDNF polyclonal antibodies were used. Western blot analysis on homogenates of human and rat brain and recombinant human GDNF resulted in differential detection of monomeric and dimeric forms of the proteins. The ABC immunohistochemical technique revealed that in the Ammon’s horn, numerous positive cell bodies occurred in the pyramidal layer, the majority of them being present in the proximal CA1 and in CA2. Sparse positive neurons could be observed in the stratum oriens and moleculare. In the fascia dentata many granule cells showed a light punctate staining, whereas more heavily labelled neurons occurred in the polymorphic layer and, occasionally, in the molecular layer. The distribution pattern of GDNF-like immunoreactivity appeared consistently similar throughout life stages from 29 w.g. to adult age. However, intensity of labelling and frequency of neuronal cell bodies was highest in the neonate and decreased in adulthood. The present data provide a comprehensive map of the localization of GDNF-like immunoreactive neurons in the human archicortex at developmental ages and in the mature tissue and represent a first step towards the identification of hippocampal neurons which express the protein and/or are responsive to it. They further suggest that GDNF may play a role in the development of intrahippocampal circuitry and in neuronal function and maintenance throughout life.