Absence of hippocampal mossy fiber sprouting in transgenic mice overexpressing brain-derived neurotrophic factor

Excess neuronal activity upregulates the expression of two neurotrophins, n erve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in ad ult hippocampus. Nerve growth factor has been shown to contribute the induc tion of aberrant hippocampal messy fiber sprouting in the inner molecular l ayer of the dentate gyrus, however the role of prolonged brain-derived neur otrophic factor exposure is uncertain. We examined the distribution and pla sticity of messy fibers in transgenic mice with developmental overexpressio n of brain-derived neurotrophic factor. Despite 2-3-fold elevated BDNF leve ls in the hippocampus sufficient to increase the intensity of neuropeptide Y immunoreactivity in interneurons, no visible changes in messy fiber Timm staining patterns were observed in the inner molecular layer of adult mutan t hippocampus compared to wild-type mice, In addition, no changes of the mR NA expression of two growth-associated proteins, GAP-43 and SCG-10 were fou nd, These data suggest that early and persistent elevations of brain-derive d neurotrophic factor in granule cells are not sufficient to elicit this pa ttern of axonal plasticity in the hippocampus, (C) 2001 Wiley-Liss, Inc.