Distribution of brain-derived neurotrophic factor and TrkB receptor proteins in the fetal and postnatal hippocampus and cerebellum of the guinea pig.

This study investigates the distribution of brain-derived neurotrophic factor protein (BDNF) and its receptor, TrkB, during the development of hippocampus and cerebellum in a long-gestation species, the guinea pig. In the granule cell populations of both structures, BDNF immunoreactivity (-IR) was exclusive to postmigratory, mature neurons. In dentate granule cells, TrkB-IR was coexpressed with BDNF-IR, suggesting that the ligand-receptor interaction could occur by means of an autocrine/paracrine mechanism. In cerebellar granule cells, TrkB-IR was detected in both pre- and postmigratory cells, indicating that immature neurons are also BDNF-responsive. With advancing gestational age an increase in the intensity of BDNF-IR in granule cells was accompanied by concomitant increases in the staining and areal growth of the associated mossy fiber layer in the hippocampus, and the molecular layer in the cerebellum. The developmental increase in BDNF- and TrkB-IR in the neuropil of both structures coincided with periods of significant growth in all strata, indicating a role for BDNF and TrkB in process outgrowth. In the hippocampus, CA2, CA3, and hilar, neurons demonstrated both BDNF- and TrkB-IR during development and maturation, whereas CA1 neurons showed TrkB-IR throughout this period but only transient BDNF-IR in early gestation. In the fetal cerebellum, Purkinje cell bodies coexpressed BDNF-IR and TrkB-IR. In the postnatal period, BDNF-IR was down-regulated but TrkB-IR persisted, indicating that mature Purkinje cells might retain their responsiveness to BDNF. Thus, we have demonstrated in both the hippocampus and cerebellum that the spatiotemporal distribution of BDNF-IR and TrkB-IR coincides with the maturation of granule cells prenatally and with significant periods of neuropil growth, both prenatally and in the immediate postnatal period. Copyright 2002 Wiley-Liss, Inc.