Neurotrophins secreted by the postsynaptic target cell may participate in activity-dependent synaptic modification during development and in the mature brain. A fundamental question of how neurotrophins can sculpt synaptic connections is whether neurotrophin-induced synaptic changes are spatially restricted to the site of neurotrophin secretion or whether they can spread to neighboring synapses...

Prolonged or high-intensity exposure to visible light leads to photoreceptor cell death. In this study, we demonstrate a novel pathway of light-induced photoreceptor apoptosis involving the low-affinity neurotrophin receptor p75 (p75NTR). Retinal degeneration upregulated both p75NTR and the high-affinity neurotrophin receptor TrkC in different parts of Müller glial cells. Exogenous neurotrophin...

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) are three representative neurotrophins responsible for the differentiation and survival of neurons, and their high-affinity receptors are tropomyosin-receptor-kinase (TRK)A, TRKB, and TRKC, respectively. In this study, we investigated the expression of neurotrophins in a mouse periodontal ligament cel...

Recent work has shown that neurotrophin gene expression is increased after seizures evoked in the kindling model of epilepsy, but whether neurotrophins regulate kindling development is as yet unclear. In this study, we attempted to block selectively the activation of distinct neurotrophin receptors throughout kindling development in the rat via chronic intracerebroventricular administration of ...

The objective of this study was to determine the effect of neurotrophin-secreting Schwann cell implants on the urinary bladder after spinal cord contusion. One hour after severe spinal cord contusion at the T8 to T11 level, carbon filaments containing nonsecreting Schwann cells, brain-derived neurotrophic factor (BDNF)-secreting Schwann cells, neurotrophin-3 (NT-3)-secreting Schwann cells, or S...

Establishment of neuronal circuitry depends on both formation and refinement of neural connections. During this process, target-derived neurotrophins regulate both transcription and translation to enable selective axon survival or elimination. However, it is not known whether retrograde signaling pathways that control transcription are coordinated with neurotrophin-regulated actions that transp...

The receptor tyrosine kinase, TrkB, is critical to diverse functions of the mammalian nervous system in health and disease. Evidence of TrkB activation during epileptogenesis in vivo despite genetic deletion of its prototypic neurotrophin ligands led us to hypothesize that a non-neurotrophin, the divalent cation zinc, can transactivate TrkB. We found that zinc activates TrkB through increasing ...

Trk tyrosine kinases are receptors for members of the neurotrophin family and are crucial for growth and survival of specific populations of neurons. Yet, the functions of neurotrophin-Trk signaling in postnatal development as well as maintenance and plasticity of the adult nervous system are less clear. We report here the generation of mice harboring Trk knockin alleles that allow for pharmaco...

Retinal ganglion cell (RGC) survival and neurite outgrowth were investigated in retinal explants from adult rats. Neurotrophin-4/5 (NT-4/5) caused dose-dependent increases in neurite outgrowth with one-half maximal effects at approximately 0.5 ng/ml and maximal effects at 5 ng/ml. In explants treated for 7 days, the actions of NT-4/5 were similar to those of brain-derived neurotrophic factor (B...

The induction of neurite outgrowth and arborization is critical for developmental and regenerative processes. In this paper, we report that the BTB-kelch protein KLHL20 promoted neurite outgrowth and arborization in hippocampal and cortical neurons through its interaction with Cullin3 to form a ubiquitin ligase complex. This complex targeted PDZ-Rho guanine nucleotide exchange factor (RhoGEF), ...