BDNF and TrkB protein expression is altered in the fetal hippocampus but not cerebellum after chronic prenatal compromise.

This study examines the effects of a chronic prenatal insult on both the expression of brain-derived neurotrophic factor (BDNF) and TrkB proteins and the structural development of the fetal hippocampus and cerebellum. Chronic placental insufficiency (CPI) was induced via unilateral ligation of the uterine artery from midgestation to near term in the pregnant guinea pig. Fetuses were delivered at 60 days of gestation (dg, term approximately 67 dg) and classified as control or growth-restricted (GR) according to established criteria. In hippocampi and cerebella from control (n = 7) and GR (n = 8) fetuses, immunohistochemistry was performed to detect the expression of BDNF and TrkB proteins, and the growth of neuropil and cellular layers was measured in each structure. The growth of neuropil layers was reduced in the dentate gyrus of GR fetuses compared to controls: hippocampi from severely GR fetuses showed a marked reduction in BDNF-IR and an increase in TrkB-IR. The most pronounced effects on neuropil growth were seen in the same fetuses that demonstrated marked alterations in BDNF-IR and TrkB-IR. In the cerebellum, there were significant reductions in the growth of the cellular and neuropil layers; however, BDNF-IR and TrkB-IR were not affected. These results demonstrate that CPI has a widespread effect in retarding process growth in the developing brain, but a differential effect on neurotrophin expression. Changes in BDNF and TrkB expression appear to be associated with the pronounced structural changes in the hippocampi of severely GR fetuses, however, structural abnormalities in the cerebellum were not associated with changes in these proteins; presumably, other factors are involved.