Loss of neurotrophin-3 from smooth muscle disrupts vagal gastrointestinal afferent signaling and satiation.

A large proportion of vagal afferents are dependent on neurotrophin-3 (NT-3) for survival. NT-3 is expressed in developing gastrointestinal (GI) smooth muscle, a tissue densely innervated by vagal mechanoreceptors, and thus could regulate their survival. We genetically ablated NT-3 from developing GI smooth muscle and examined the pattern of loss of NT-3 expression in the GI tract and whether this loss altered vagal afferent signaling or feeding behavior.

Expression profiling of Huntington's disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration.

Many pathways have been proposed as contributing to Huntington's disease (HD) pathogenesis, but generally the in vivo effects of their perturbation have not been compared with reference data from human patients. Here we examine how accurately mechanistically motivated and genetic HD models recapitulate the striatal gene expression phenotype of human HD. The representative genetic model was the R6/2 transgenic mouse, which expresses a fragment of the huntingtin protein containing a long CAG repeat.

Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta.

Brain-derived neurotrophic factor (BDNF) has been implicated in regulating neuronal survival, differentiation, and synaptic plasticity. Reduced expression of BDNF within the substantia nigra accompanies the deterioration of dopaminergic neurons in Parkinson's disease (PD) patients. Analysis of the effects of long-term BDNF absence from the CNS has been difficult because of the early postnatal lethality of BDNF-/- mice.

Early striatal dendrite deficits followed by neuron loss with advanced age in the absence of anterograde cortical brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, modulates neuronal survival, differentiation, and synaptic function. Reduced BDNF expression in the cortex caused by mutation of the huntingtin gene has been suggested to play a role in the striatal degeneration observed in Huntington's disease. BDNF expression rises dramatically in the cortex during the first few weeks of postnatal life in mice.

Neurotrophin-3 is expressed in a discrete subset of olfactory receptor neurons in the mouse.

In transgenic neurotrophin-3 lacZ-neo (NT-3(lacZneo)) mice, in which the coding region for NT-3 is replaced by Eschericia coli lacZ, the expression of beta-galactosidase faithfully mimics the expression of NT-3 (Vigers AJ, Baquet ZC, Jones KR [2000], J Comp Neurol 416:398-416). During embryonic and early postnatal development, beta-galactosidase is detected in the olfactory system, beginning at embryonic day 11.5 in the nasal epithelium and at embryonic day 16.