Dendrite extension

Abstract: We previously reported that the methanol extract of Ashwagandha (roots of Dunal) induced dendrite extension in a human neuroblastoma cell line. In this study, we found that six of the 18 compounds isolated from the methanol extract enhanced neurite outgrowth in human neuroblastoma SH-SY5Y cells. Double immunostaining was performed in rat cortical neurons using antibodies to phosphorylated NF-H as an axonal marker, and to MAP2 as a dendritic marker. In withanolide A-treated cells, the length of NF-H-positive processes was significantly increased compared with vehicle-treated cells, whereas, the length of MAP2-positive processes was increased by withanosides IV and VI. These results suggest that axons are predominantly extended by withanolide A, and dendrites by withanosides IV and VI.

Abstract: Newborn granule cells become functionally integrated into the synaptic circuitry of the adult dentate gyrus after a morphological and electrophysiological maturation process. The molecular mechanisms by which immature neurons and the neurites extending from them find their appropriate position and target area remain largely unknown. Here we show that single-cell–specific knockdown of cyclin-dependent kinase 5 (cdk5) activity in newborn cells using a retrovirus-based strategy leads to aberrant growth of dendritic processes, which is associated with an altered migration pattern of newborn cells. Even though spine formation and maturation are reduced in cdk5-deficient cells, aberrant dendrites form ectopic synapses onto hilar neurons. These observations identify cdk5 to be critically involved in the maturation and dendrite extension of newborn neurons in the course of adult neurogenesis. The data presented here also suggest a mechanistic dissociation between accurate dendritic targeting and subsequent synapse formation.

Abstract: Epidermal Langerhans cells (LC) are potent dendritic cells in the induction of primary T cell-mediated immune responses in the skin. They capture foreign Ags and migrate to regional lymph nodes to carry and present these Ags to naive T cells. We investigated the role of matrix metalloproteinase-9 (MMP-9) in LC migration using an anti-MMP-9 mAb. Intradermal injection of anti-MMP-9 mAb before rhodamine B or oxazolone painting markedly inhibited these hapten-induced decreases in LC number in the epidermis and the accumulation of dendritic cells in the regional lymph nodes, indicating that MMP-9 plays some important roles in LC migration in the induction phase of contact sensitization. Treatment with anti-MMP-9 mAb also blocked the increase in cell size, dendrite development, and the enhanced expression of MHC class II Ags in LC induced by hapten painting. In addition, intradermal injection of purified MMP-9 induced marked increases in cell size, dendrite extension, and enhanced expression of MHC class II Ags in LC. These results strongly suggested that MMP-9 is involved not only in LC migration, but also in their morphological and phenotypic maturation in the skin.

Abstract: It is known that cerebellar granule cells are powerful inducers for the differentiation of Purkinje cells However, the detailed mechanism of this regulation has not yet been clarified Here, using cerebellar neuronal culture, we show that the activation of NMDA receptors expressed by granule cells triggers the signaling pathway for the dendritic differentiation of Purkinje cells This signal has been shown to promote the granule cell survival through BDNF-mediated TrkB activation, leading to Purkinje cell differentiation by increasing the granule-Purkinje cell interaction Among the possible signal molecules provided to the dendrites of Purkinje cells from granule cells, nitric oxide was found to have no effect on the dendritic outgrowth and branching, but electrical activity and the subsequent intracellular Ca(2+) increase were thought to play an important role in the branching and thickening of the dendrites, because blockade of both non-NMDA and metabotropic glutamate receptors caused a significant decrease in the number of branch points and the diameter of Purkinje dendrites without apparently affecting the dendrite extension and spine formation Collectively, these results suggest that Purkinje cell differentiation is regulated by two successive steps The first step is initiated by the NMDA receptor-mediated signal in granule cells, which acts as a trophic factor for granule cells The second step involves the activation of granule-Purkinje synapses, providing neurotrophic substances and electrical activity essential for Purkinje cell differentiation