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PubMed2001

Characterization of antigen-presenting dendritic cells in the peripheral blood and colonic mucosa of patients with ulcerative colitis.

OBJECTIVE: Increased lymphocyte activation and production of inflammatory cytokines are implicated in the pathogenesis of ulcerative colitis. Because antigen-presenting dendritic cells play a cardinal role in the activation and survival of activated lymphocytes, the aim of the present study was to characterize dendritic cells in ulcerative colitis. DESIGN: This study was designed to compare the phenotypes and functions of peripheral blood dendritic cells among healthy normal volunteers and patients with ulcerative colitis or Crohn's disease. Activated dendritic cells were also localized at the colonic mucosa. METHODS: Peripheral blood dendritic cells were generated from 15 patients with ulcerative colitis, 10 patients with Crohn's disease and 15 healthy control volunteers. The stimulatory capacities of dendritic cells were analysed in an allogenic mixed lymphocyte reaction. Nitric oxide was detected by the Griess method. Single- and dual-colour flow cytometry was employed to study the levels of maturation of dendritic cells. Activated dendritic cells were localized immunohistochemically in the colonic mucosa. RESULTS: In comparison to normal controls, peripheral blood dendritic cells from patients with ulcerative colitis showed significantly increased stimulatory capacities (P < 0.05) and produced significantly higher levels of nitric oxide (P < 0.05). The numbers of activated dendritic cells were also significantly higher in ulcerative colitis (P < 0.05). Mature and activated dendritic cells expressing the CD83 antigen were detected at the inflamed colonic mucosa in patients with ulcerative colitis and Crohn's disease. CONCLUSIONS: Activated and mature dendritic cells may have a role in the induction of an exacerbated immune response in ulcerative colitis. This study provides the scientific and logical basis for blocking the maturation and activation of dendritic cells in ulcerative colitis as a new therapeutic intervention.

Adult↗
PubMed1995

Maturation and migration of cutaneous dendritic cells.

Dendritic cells have been isolated from the epidermis, dermis, and lymphatics of skin. Cells from each cutaneous compartment can exhibit the distinct morphology, surface phenotype, and strong T-cell-stimulating activity of dendritic cells that are isolated from other organs. Of importance are the mechanisms by which the maturation and movement of dendritic cells are regulated within intact tissues. Epidermal dendritic cells turn over slowly in the steady state. Stimuli, including contact allergens and transplantation, perhaps by inducing a release of cytokines such as granulocyte macrophage-colony-stimulating factor, mobilize these dendritic cells into the dermis and lymph. This migration is accompanied by the maturation of dendritic cell functions; e.g., antigen-presenting major histocompatibility complex molecules and B7 costimulators increase markedly. On the other hand, there is a sizable, steady-state flux of dendritic cells in afferent lymph draining the skin, which suggests a constant traffic through the dermis that is independent of sessile epidermal dendritic cells. When explants of skin are placed in organ culture, dendritic cells emigrate into the medium for 1-3 d. The dendritic cells are mature and can bind tightly to small memory T cells that also migrate in these cultures. The emigrated mixtures of dendritic cells and T cells should be useful in the study of many clinical states. This is illustrated by recent experiments showing that migratory skin cells are readily infected with human immunodeficiency virus (HIV)-1. A strong productive infection takes place in the absence of exogenous cytokines, foreign sera, or mitogens or antigens. The dendritic cell-T-cell conjugates are the essential site for infection. This cellular milieu may model events during the sexual transmission of HIV-1, where relevant mucosal surfaces are covered by skin-like epithelia. The capture of CD4+ memory T cells by dendritic cells may explain the chronic drain of immune memory in HIV infection.

Animals↗
PubMed1994

Dendritic cells in cutaneous lupus erythematosus: a clue to the pathogenesis of lesions.

In view of the critical role of dendritic cells in immune mediated skin diseases, we have investigated the membrane antigen patterns and ultrastructure of cutaneous dendritic cells in eight patients with chronic discoid lupus erythematosus and five with subacute cutaneous lupus erythematosus. In the lesional epidermis, the expression of HLA-DR antigens by epidermal dendritic cells was reduced, as compared with perilesional, clinically normal skin. In addition, only few CD1a+ dendritic cells (Langerhans' cells), along with some CD11c+ and CD14+ cells (presumable precursors of Langerhans' cells), were found in atrophic areas of lesional epidermis. In contrast, the number of Langerhans' cells in non-atrophic areas of lesional epidermis was similar to that in perilesional skin. On electronmicroscopy, epidermal Langerhans' cells appeared depleted of organelles and dendrites and contained tubuloreticular inclusions. In the lesional dermis, both CD1a+ and CD36+ dendritic cells were found, associated with CD4+ and CD8+ T-cells, respectively. Moreover, CD11c+ and CD14+ cells were found around capillaries in the papillary dermis on electronmicroscopy. Indeterminate cells (dendritic cells with features of Langerhans' cell lineage, but apparently without Birbeck granules) and dendritic macrophages were found, associated with lymphocytes and mast cells. No cells with intermediate/transitional features between these two dendritic cell types were found. Conversely, peculiar dendritic cells--with short and blunt dendrites and cytoplasm containing many flat, rough cisternae, moderately well developed Golgi apparatus and no lysosomes--were found in the same location as the CD11c+ and CD14+ cells identified by light microscopy. These findings might be interpreted as follows: 1 the alterations in cytological differentiation and expression of functionally meaningful molecules by epidermal Langerhans' cells in cutaneous lupus erythematosus lesions suggest an impairment of their immunological efficiency; 2 in the lesional dermis of cutaneous lupus erythematosus, a CD4+ T-cell/CD1a+ dendritic cell-based, delayed-type immune response is possibly modulated by a suppressor T-cell circuit in which CD36+ dendritic cells may act as accessory cells; 3 CD11c+ and CD14+ cells with peculiar ultrastructure are possible precursors of both CD1a+ indeterminate cells and CD36+ dermal dendrocytes in the dermis.

Adolescent↗
PubMed1997

Action potential propagation into the presynaptic dendrites of rat mitral cells.

1. Dendritic patch-clamp recordings were obtained from mitral cells in rat olfactory bulb slices, up to 350 microns from the soma. Simultaneous dendritic and somatic whole-cell recordings indicated that action potentials (APs) evoked by somatic or dendritic current injection were initiated near the soma. Both the large amplitude (100.7 +/- 1.1 mV) and the short duration (1.38 +/- 0.07 ms) of the AP were maintained as the AP propagated back into the primary mitral cell dendrites. 2. Outside-out patches isolated from mitral cell dendrites contained voltage-gated Na+ channels (peak conductance density, 90 pS micron-2 at -10 mV). When an AP was used as a somatic voltage-clamp command in the presence of 1 microM tetrodotoxin (TTX), the amplitude of the dendritic potential was attenuated to 48 +/- 14 mV. This shows that dendritic Na+ channels support the active back-propagation of APs. 3. Dendritic patches contained voltage-gated K+ channels with high density (conductance density, 513 pS micron-2 at 30 mV). Dendritic K+ currents were reduced to 35% by 1 mM external tetraethylammonium chloride (TEACl). When an AP was used as a somatic voltage-clamp command in the presence of TEACl, the dendritic potential was markedly prolonged. This indicates that dendritic K+ channels mediate the fast repolarization of dendritic APs. 4. We conclude that voltage-gated Na+ and K+ channels support dendritic APs with large amplitudes and short durations that may trigger fast transmitter release at dendrodendritic synapses in the olfactory bulb.

Action Potentials↗
PubMed1994

A branching dendritic model of a rodent CA3 pyramidal neurone.

1. We constructed a branching dendritic compartmental model of a CA3 pyramidal neurone, using experimental data from guinea-pig and rat cells obtained in vitro. The goal was to understand interactions between synaptic events impinging on dendritic branches and voltage- and calcium-dependent currents. The model contained sixty-four soma-dendrite (SD) compartments, an axon initial segment (IS), and four axonal compartments. There were six active conductances in the SD membrane, including a sodium conductance (gNa) and a high-threshold calcium conductance (gCa), with kinetic properties similar to those reported in a previous study. 2. The distribution of conductance densities across the IS and SD was adjusted by testing the model response to antidromic stimulation and current pulses or sustained currents injected into the soma or apical dendrites. As before, gNa was concentrated on and near the soma with lower density in the dendrites, while gCa had a higher density in apical dendrites than at the soma. 3. The model predicts that CA3 pyramidal neurones in media blocking synaptic transmission should fire a burst of action potentials following antidromic stimulation. This was confirmed experimentally in hippocampal slices. 4. Both in the model and in guinea-pig neurones, dendritic IPSCs can delay the onset of bursting. If an IPSC begins soon enough after the first fast action potential, the later burst envelope is attenuated. This effect results from suppression of dendritic Ca2+ electrogenesis. 5. The model predicts that an appropriately timed dendritic IPSC (after the first somatic spike but before the dendritic Ca2+ spike) may suppress the transient local [Ca2+] signal, while having a negligible effect on the electrical output of the neurone. This phenomenon has been reported in guinea-pig Purkinje cells. 6. We conclude that active dendritic currents are critical for regulation of the electrical output of CA3 pyramidal neurones. We suggest also that dendritic [Ca2+] signals might be controlled in individual dendrites independently of action potential outputs, an effect of possible importance for synaptic plasticity.

Action Potentials↗
PubMed2002

Molecular control of cortical dendrite development.

Dendritic morphology has a profound impact on neuronal information processing. The overall extent and orientation of dendrites determines the kinds of input a neuron receives. Fine dendritic appendages called spines act as subcellular compartments devoted to processing synaptic information, and the dendritic branching pattern determines the efficacy with which synaptic information is transmitted to the soma. The acquisition of a mature dendritic morphology depends on the coordinated action of a number of different extracellular factors. Here we discuss this evidence in the context of dendritic development in the cerebral cortex. Soon after migrating to the cortical plate, neurons extend an apical dendrite directed toward the pial surface. The oriented growth of the apical dendrite is regulated by Sema3A, which acts as a dendritic chemoattractant. Subsequent dendritic development involves signaling by neurotrophic factors and Notch, which regulate dendritic growth and branching. During postnatal development the formation and stabilization of dendritic spines are regulated in part by patterns of synaptic activity. These observations suggest that extracellular signals play an important role in regulating every aspect of dendritic development and thereby exert a critical influence on cortical connectivity.

Animals↗
PubMed2006

Simple models show the general advantages of dendrites in coincidence detection.

Dendrites can influence and improve information processing in single neurons. Here, simple models are used to elucidate mechanisms underlying the dendritic enhancement of coincidence detection. We focus on coincidence-detecting cells in the auditory system, which have bipolar dendrites and show acute sensitivity to interaural time difference (ITD), a critical cue for spatial hearing. A three-compartment model consisting of a single-compartment soma and two single-compartment dendrites is primarily used, although multiple-compartment dendrites are also tested. Two varieties of somata, with and without active ion channels, are studied. Using constant conductance inputs, we show analytically that the somatic response to balanced bilateral inputs is largest, whereas the response monotonically decreases as the input distribution becomes increasingly monolateral. This enhancement is a consequence of the sublinear saturating dendritic voltage response to conductance input and occurs when dendrites are composed of a single compartment or either a finite number or an infinite number (i.e., a cable) of compartments. Longer, thinner dendrites or greater numbers of compartments increase the enhancement of the somatic response to bilateral input. The time-independent dendritic enhancement, moreover, underlies improved coincidence detection of time-varying input. Coincidence sensitivity to a pair of conductance pulses and rate-ITD modulation to low-frequency (400-Hz) periodic inputs increases with dendritic length. These findings are related to the length gradient in the avian system, where low characteristic frequency (CF) cells have long dendrites and high CF cells have short dendrites. We conclude that dendrites fundamentally improve coincidence detection, increasing the computational power of many neurons in the nervous system.

Action Potentials↗
PubMed1992

A model of NMDA receptor-mediated activity in dendrites of hippocampal CA1 pyramidal neurons.

1. The role of synaptic activation of NMDA (N-methyl-D-aspartate) receptor-mediated conductances on CA1 hippocampal pyramidal cells in short-term excitability changes was studied with the use of a computational model. Model parameters were based on experimental recordings from dendrites and somata and previous hippocampal simulations. Representation of CA1 neurons included NMDA and non-NMDA excitatory dendritic synapses, dendritic and somatic inhibition, five intrinsic membrane conductances, and provision for activity-dependent intracellular and extracellular ion concentration changes. 2. The model simulated somatic and dendritic potentials recorded experimentally. The characteristic CA1 spike afterdepolarization was a consequence of the longitudinal spread of dendritic charge, reactivation of slow Ca(2+)-dependent K+ conductances, slow synaptic processes (NMDA-dependent depolarizing and gamma-aminobutyric acid-mediated hyperpolarizing currents) and was sensitive to extracellular potassium accumulation. Calcium currents were found to be less important in generating the spike afterdepolarization. 3. Repetitive activity was influenced by the cumulative activation of the NMDA-mediated synaptic conductances, the frequency-dependent depression of inhibitory synaptic responses, and a shift in the potassium reversal potential. NMDA receptor activation produced a transient potentiation of the excitatory postsynaptic potential (EPSP). The frequency dependence of EPSP potentiation was similar to the experimental data, reaching a maximal value near 10 Hz. 4. Although the present model did not have compartments for dendritic spines, Ca2+ accumulation was simulated in a restricted space near the intracellular surface of the dendritic membrane. The simulations demonstrated that the Ca2+ component of the NMDA-operated synaptic current can be a significant factor in increasing the Ca2+ concentration at submembrane regions, even in the absence of Ca2+ spikes. 5. Elevation of the extracellular K+ concentration enhanced the dendritic synaptic response during repetitive activity and led to an increase in intracellular Ca2+ levels. This increase in dendritic excitability was partly mediated by NMDA receptor-mediated conductances. 6. Blockade of Ca(2+)-sensitive K+ conductances in the dendrites increased the size of EPSPs leading to a facilitation of dendritic and somatic spike activity and increased [Ca2+]i. NMDA receptor-mediated conductances appeared as an amplifying component in this mechanism, activated by the relatively depolarized membrane potential. 7. The results suggest that dendritic NMDA receptors, by virtue of their voltage-dependency, can interact with a number of voltage-sensitive conductances to increase the dendritic excitatory response during periods of repetitive synaptic activation. These findings support experimental results that implicate NMDA receptor-mediated conductances in the short-term response plasticity of the CA1 hippocampal pyramidal neuron.

Animals↗
PubMed1996

Dendritic Na+ channels amplify EPSPs in hippocampal CA1 pyramidal cells.

1. Whole cell recordings were performed on the somata of CA1 pyramidal neurons in the rat hippocampal slice preparation Remote synaptic events were evoked by electrical stimulation of Schaffer collateral/commissural fibers in outer stratum radiatum. To isolate non-N-methyl-D-aspartate (NMDA)-mediated excitatory postsynaptic potentials (EPSPs), bath solutions contained the NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (D-APV; 30 microM), the gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline (10 microM), and the GABAB receptor antagonists, CGP 35348 (30 microM) or, in some experiments, saclofen (100 microM). 2. Local application of tetrodotoxin (TTX; 0.5-10 microM) into the proximal region of the apical dendrite reduced the peak amplitude of somatically recorded EPSPs by 28% on average. In contrast to dendritic TTX application, injection of TTX into the axosomatic region of the recorded neuron reduced EPSP amplitude by only 12% on average. 3. Spill-over of dendritically applied TTX into stratum pyramidale or into outer stratum radiatum was ruled out experimentally: somatic action potentials and field EPSPs recorded near the stimulation site in outer stratum radiatum remained unaffected by local TTX application. 4. Variations of somatic membrane potential revealed a strong voltage dependence of EPSP reduction after dendritic TTX application with the effect increasing substantially with membrane depolarization. Together with the field recordings from stratum radiatum, this finding argues strongly against a predominantly presynaptic site of TTX action. 5. We therefore ascribe the EPSP decrease after local TTX application to the proximal dendrite to suppression of dendritic Na+ channels, which we assume to give rise to a noninactivating (persistent) Na+ current (INaP) in the subthreshold voltage range. Our data suggest that presumed dendritic INaP produces considerable elevation of remote excitatory signals, thereby compensating for much of their electrotonic attenuation. 6. The experimental findings were related to computer simulations performed on a reduced compartmental model of the CA1 neuron. Because the experimental evidence available so far yields only indirect clues on the strength and distribution of INaP, we allowed considerable variations in these parameters. We also varied both size and location of synaptic input. 7. The major conclusions drawn from these simulations are the following: somatic INaP alone produces little EPSP enhancement; INaP density at the axon hillock/initial segment has to be at least twice the density at the soma to produce substantial EPSP amplification; depending on the density and distribution of dendritic INaP, < or = 80% of a remote synaptic potential arrives at the soma (compared with only 52% in a passive dendrite); synaptic potentials receive progressively more elevation by dendritic INaP the stronger they are; even if restricted to the proximal segment of the apical dendrite, INaP also affects dendritic processing at more distal segments; and spatial distribution rather than local density appears to be the most important parameter determining the role of dendritic INaP in synaptic integration.

Animals↗
PubMed1997

Local and propagated dendritic action potentials evoked by glutamate iontophoresis on rat neocortical pyramidal neurons.

Iontophoresis of glutamate at sites on the apical dendrite 278-555 microm from the somata of rat neocortical pyramidal neurons evoked low-threshold, small, slow spikes and/or large, fast spikes in 71% of recorded cells. The amplitude of the small, slow spikes recorded at the soma averaged 9.1 mV, and their apparent threshold was <10 mV positive to resting potential. Both their amplitude and their apparent threshold decreased as the iontophoretic site was moved farther from the soma. These spikes were not abolished by somatic hyperpolarization. When the somata of cells displaying these small spikes were voltage clamped at membrane potentials that prevented somatic or axonic firing, corresponding current spikes could be evoked all-or-none by dendritic depolarization, indicating that the small, slow spikes arose in the dendrite. Similar responses were not observed during somatic depolarization evoked by current pulses or glutamate iontophoresis. These small, slow spikes were abolished by blocking voltage-gated Ca2+ channels but not by blocking Na+ channels or N-methyl-D-aspartate receptors. We conclude that these Ca2+ spikes occurred in a spatially restricted region of the dendrite and were not actively propagated to the soma. In the presence of 10 mM tetraethylammonium chloride, the amplitudes of the iontophoretically evoked Ca2+ spikes were large, similar to those of the Ca2+ spikes evoked by somatic current injection, but their apparent thresholds were 63% lower. We conclude that dendritic K+ channels normally prevent the active propagation of Ca2+ spikes along the dendrite. In 36% of recorded cells dendritic glutamate iontophoresis evoked a Na+ spike with an apparent threshold 63% lower than those evoked by somatic current injection or somatic glutamate iontophoresis. Blockade of these low-threshold Na+ spikes by pharmacological or electrophysiological means often revealed underlying small dendritic Ca2+ spikes. When cells displaying the low-threshold Na+ spikes were voltage clamped at membrane potentials that prevented firing of the soma or axon, corresponding tetrodotoxin-sensitive current spikes could be evoked all-or-none by dendritic depolarization. We conclude that these low-threshold Na+ spikes were initiated in the dendrite, probably by local Ca2+ spikes, and subsequently propagated actively to the soma. Most cells displaying dendritic Na+ spikes fired multiple bursts of action potentials during tonic dendritic depolarization, whereas somatic depolarization of the same cells evoked only regular firing. We discuss the implications of dendritic Ca2+ and Na+ spikes for synaptic integration and neural input-output relations.

Animals↗
PubMed1999

Impulse encoding across the dendritic morphologies of retinal ganglion cells.

Nerve impulse entrainment and other excitation and passive phenomena are analyzed for a morphologically diverse and exhaustive data set (n = 57) of realistic (3-dimensional computer traced) soma-dendritic tree structures of ganglion cells in the tiger salamander (Ambystoma tigrinum) retina. The neurons, including axon and an anatomically specialized thin axonal segment that is observed in every ganglion cell, were supplied with five voltage- or ligand-gated ion channels (plus leakage), which were distributed in accordance with those found in a recent study that employed an equivalent dendritic cylinder. A wide variety of impulse-entrainment responses was observed, including regular low-frequency firing, impulse doublets, and more complex patterns involving impulse propagation failures (or aborted spikes) within the encoder region, all of which have been observed experimentally. The impulse-frequency response curves of the cells fell into three groups called FAST, MEDIUM, and SLOW in approximate proportion as seen experimentally. In addition to these, a new group was found among the traced cells that exhibited an impulse-frequency response twice that of the FAST category. The total amount of soma-dendritic surface area exhibited by a given cell is decisive in determining its electrophysiological classification. On the other hand, we found only a weak correlation between the electrophysiological group and the morphological classification of a given cell, which is based on the complexity of dendritic branching and the physical reach or "receptive field" area of the cell. Dendritic morphology determines discharge patterns to dendritic (synaptic) stimulation. Orthodromic impulses can be initiated on the axon hillock, the thin axonal segment, the soma, or even the proximal axon beyond the thin segment, depending on stimulus magnitude, soma-dendritic membrane area, channel distribution, and state within the repetitive impulse cycle. Although a sufficiently high dendritic Na-channel density can lead to dendritic impulse initiation, this does not occur with our "standard" channel densities and is not seen experimentally. Even so, impulses initiated elsewhere do invade all except very thin dendritic processes. Impulse-encoding irregularities increase when channel conductances are reduced in the encoder region, and the F/I properties of the cells are a strong function of the calcium- and Ca-activated K-channel densities. Use of equivalent dendritic cylinders requires more soma-dendritic surface area than real dendritic trees, and the source of the discrepancy is discussed.

Action Potentials↗
PubMed1999

Geometry of dendritic spines affects calcium dynamics in hippocampal neurons: theory and experiments.

The role of dendritic spine morphology in the regulation of the spatiotemporal distribution of free intracellular calcium concentration ([Ca2+]i) was examined in a unique axial-symmetrical model that focuses on spine-dendrite interactions, and the simulations of the model were compared with the behavior of real dendritic spines in cultured hippocampal neurons. A set of nonlinear differential equations describes the behavior of a spherical dendritic spine head, linked to a dendrite via a cylindrical spine neck. Mechanisms for handling of calcium (including internal stores, buffers, and efflux pathways) are placed in both the dendrites and spines. In response to a calcium surge, the magnitude and time course of the response in both the spine and the parent dendrite vary as a function of the length of the spine neck such that a short neck increases the magnitude of the response in the dendrite and speeds up the recovery in the spine head. The generality of the model, originally constructed for a case of release of calcium from stores, was tested in simulations of fast calcium influx through membrane channels and verified the impact of spine neck on calcium dynamics. Spatiotemporal distributions of [Ca2+]i, measured in individual dendritic spines of cultured hippocampal neurons injected with Calcium Green-1, were monitored with a confocal laser scanning microscope. Line scans of spines and dendrites at a <1-ms time resolution reveal simultaneous transient rises in [Ca2+]i in spines and their parent dendrites after application of caffeine or during spontaneous calcium transients associated with synaptic or action potential discharges. The magnitude of responses in the individual compartments, spine-dendrite disparity, and the temporal distribution of [Ca2+]i were different for spines with short and long necks, with the latter being more independent of the dendrite, in agreement with prediction of the model.

Animals↗
PubMed2006

An essential role for the integrin-linked kinase-glycogen synthase kinase-3 beta pathway during dendrite initiation and growth.

Multiple cues, including growth factors and circuit activity, signal to regulate the initiation and growth of mammalian dendrites. In this study, we have asked how these environmental cues regulate dendrite formation, and in particular, whether dendrite initiation and growth requires integrin-linked kinase (ILK) or its downstream effector, glycogen synthase kinase-3beta (GSK-3beta). In cultured sympathetic neurons, NGF and neuronal depolarization activated ILK and promoted dendrite initiation and growth, and inhibition of ILK (either pharmacologically, with a dominant-negative form of ILK, or by genetic knockdown) reduced depolarization-induced dendrite formation. In sympathetic neurons, ILK phosphorylated and inhibited GSK-3beta, and inhibition of GSK-3beta (either pharmacologically, with dominant-negative GSK-3beta, or by genetic knockdown) caused robust dendrite initiation. GSK-3beta inhibition also caused dendrite initiation in cultured cortical neurons and growth of hippocampal neurons in slice cultures. GSK-3beta functioned downstream of ILK to regulate dendrite formation, because inhibition of GSK-3beta promoted dendrite initiation even when ILK was simultaneously inhibited. Moreover, GSK-3beta promoted dendrite formation in sympathetic neurons by regulating the activity of a key dendrite formation effector, the MAP (microtubule-associated protein) kinase kinase (MEK)-extracellular signal-regulated protein kinase (ERK) pathway. Specifically, inhibition of GSK-3beta led to increased ERK phosphorylation, and inhibition of MEK completely blocked the effects of GSK-3beta inhibition on dendrite initiation and growth. Thus, the ILK-GSK-3beta pathway plays a key role in regulating dendrite formation in developing mammalian neurons.

Animals↗
PubMedDate not supplied

Surgery-induced decline in circulating dendritic cells in operable cancer patients: a possible explanation of postoperative immunosuppression.

BACKGROUND/AIMS: The recent advances in the immunobiology of tumor have demonstrated the essential role of dendritic cells in anticancer immunity. Dendritic cells activate anticancer immunity by secreting interleukin-12 and by activating T helper lymphocytes, with the following production of interleukin-2. Since surgery-induced immunosuppression has been proven to be associated with a decline in the blood levels of both interleukin-2 and interleukin-12, it could depend at least in part on a transient deficiency of dendritic cells system. Unfortunately, at present there are no data about changes in circulating dendritic cell number during the postoperative period. This preliminary study was performed to evaluate the influence of surgery on dendritic cell number in the peripheral blood. METHODOLOGY: The study included 14 consecutive operable gastrointestinal tract cancer patients, who were evaluated before and at day 7 of the postoperative period. The control group consisted of 50 healthy subjects. Immature (CD 123+) and mature (CD 11+) dendritic cell subsets were measured by FACS and monoclonal antibodies. RESULTS: Cancer patients showed a significantly lower mean number of immature dendritic cells with respect to that found in controls. The mean number of mature dendritic cells was also lower in patients than in controls, without, however, significant differences. Finally, surgery induced a statistically significant decline in the mean number of both immature and mature dendritic cells, and the decrease was particularly pronounced for immature dendritic cells. CONCLUSIONS: In addition to the well-demonstrated surgery-induced lymphocytopenia, this preliminary study shows that the surgical treatment may determine a significant decrease in circulating immature and mature dendritic cells. Because of the fundamental role of dendritic cells in regulating the immune responses, surgery-induced decline in circulating dendritic cells number could play a role in determining the immunosuppressive status, which characterizes the postoperative period.

Adult↗
PubMed1985

Local order among the dendrites of an amacrine cell population.

The cholinergic amacrine cells of the rabbit retina branch within a narrow stratum of the retina's inner synaptic layer, and their dendritic fields overlap as much as 70-fold. Because each cell's dendrites have many branches, the overlap must create a dense meshwork of cholinergic dendrites. To learn how the overlapping dendrites are positioned with respect to each other, we filled the dendrites of groups of neighboring cells with Lucifer Yellow CH. The cholinergic amacrine cells were selectively stained by intraocular injection of the fluorescent molecule 4,6-diamidino-2-phenylindole. The retinas were then fixed with 2% paraformaldehyde and 0.01% glutaraldehyde. The stained cells were penetrated under visual control by Lucifer Yellow-filled micropipettes. A systematic arrangement of the dendrites was observed. When a pair of cells was injected, their dendrites were often seen to lie alongside each other. In the terminal dendritic region, there are virtually no dendrites that do not end in apposition to a dendrite of a neighboring cholinergic amacrine cell. When small clusters of nearby cells were injected, an ordered microstructure appeared. The dendrites of the cells join together to form curving bundles, which enclose spaces that rarely contain any cholinergic dendrites: the appearance of the dendritic mosaic is that of a lattice with a repeating unit roughly 10 microns in diameter. The significance of this ordering is not certain, but it is possible that the repeating structural unit participates in a modular functional arrangement.

Animals↗
PubMed1994

Independent control of dendritic and axonal form in the developing lateral geniculate nucleus.

To identify mechanisms that regulate neuronal form in the mammalian CNS, we have examined dendritic development in the lateral geniculate nucleus (LGN) during the period of segregation of retinal ganglion cell axons. The tracer Dil was used to label retrogradely LGN neurons that send their axons to primary visual cortex at different ages between embryonic day 36 (E36) and E60 in the cat. LGN neurons grow extensively during this period, in concert with the progressive restriction of ganglion cell axons from the two eyes to their appropriate eye-specific layers. At E36 neurons have simple bipolar morphology; by E60 all have acquired complex multipolar dendritic trees. During this period, soma size increases by 190% and total dendritic length increases 240%. Dendritic complexity, as measured by dendritic branch points, also increases. As dendrites grow, the number of spines increases, but their density remains constant at 0.015/micron throughout this period. Since it is known that blockade of action potential activity significantly alters the branching pattern and extent of retinal ganglion cell axonal arbors within the LGN, we also investigated whether the dendritic development of the postsynaptic LGN neurons is similarly susceptible. Following 2 weeks of the intracranial minipump infusion of TTX between E42 and E56, the morphology of LGN neurons was examined. Surprisingly in view of the striking effect of the treatment on the morphology of retinal ganglion cell axons, dendritic growth and development were essentially normal. However, the density of dendritic spines increased almost threefold, suggesting that this specific feature of dendritic morphology is highly regulated by action potential activity. These observations indicate that normally during this period of development, the previously described changes that occur in the morphology of the presynaptic inputs to LGN neurons are accompanied by a progressive growth of post-synaptic dendrites. Because the intracranial TTX infusions have almost certainly blocked all sodium action potentials, our results suggest that the basic dendritic framework of LGN neurons can be achieved even in the absence of this form of neural activity. Moreover, since the same treatment causes a profound change in the morphology of the presynaptic axons, at least some aspects of axonal and dendritic form must be controlled independently during this prenatal period of development.

Animals↗
PubMed1992

The Extent of the Dendritic Tree and the Number of Synapses in the Frog Motoneuron.

Frog motoneurons were intracellularly labelled with cobaltic lysine in the brachial and the lumbar segments of the spinal cord, and the material was processed for light microscopy in serial sections. With the aid of the neuron reconstruction system NEUTRACE, the dendritic tree of neurons was reconstructed and the length and surface area of dendrites measured. The surface of somata was determined with the prolate - oblate average ellipsoid calculation. Corrections were made for shrinkage and for optical distortion. The mean surface area of somata was 6710 microm2; lumbar motoneurons were slightly larger than brachial motoneurons. The mean length of the combined dendritic tree of brachial neurons was 29 408 microm and that of lumbar neurons 46 806 microm. The mean surface area was 127 335 microm2 in brachial neurons, and 168 063 microm2 in lumbar neurons. The soma - dendrite surface area ratio was 3 - 5% in most cases. Dendrites with a diameter of </= 1.0 microm constituted approximately 75% of the combined dendritic length in most of the neurons. Unlike in the cat, there was no correlation between the size of stem dendrites and the extent of daughter branches. From the synaptic density estimated in earlier electron microscope investigations of frog motoneuron dendrites (Antal et al., J. Neurocytol., 15, 303 - 310, 1986; 21, 34 - 49, 1992), and from the present data, the number of synapses on the dendritic tree was calculated. The calculations indicated 26 949 synapses on the smallest and 61 519 synapses on the largest neuron if the synaptic density was multiplied by the length of the dendritic tree. If the synaptic density was multiplied by the surface area of the dendritic tree the calculation yielded 23 337 synapses for the smallest and 60 682 synapses for the largest neuron. More than 60% of the combined surface area of dendrites was >600 microm from the soma. This suggests that about two-thirds of the synapses impinged upon distant dendrites >600 microm from the soma. The efficacy of synapses at these large distances is investigated on model neurons in the accompanying paper (Wolf et al., Eur. J. Neurosci., 4 1013 - 1021, 1992).

Journal Article↗
PubMed1996

Target-specific differences in the dendritic morphology and neuropeptide content of neurons in the rat SCG during development and aging.

Our purpose in this work was to investigate the role of target tissues in the regulation of dendritic morphology from sympathetic neurons during development and aging. Neurons were retrogradely labeled from three targets, the iris, the submandibular gland (SMG), and the middle cerebral artery (MCA). They were then fixed and intracellularly injected to demonstrate their dendritic arborizations. Dendritic geometry varied quantitatively in sympathetic neurons innervating different target tissues at all stages of development. Neurons innervating the iris had the largest cell bodies and most extensive dendritic arborizations, whereas the vasomotor neurons were the smallest. The number of primary dendrites, however, did not vary significantly between the different neuronal populations. The growth of dendritic arborizations during postnatal development and their atrophy in old age were not concordant in the different neuron populations we studied. Neurons innervating the MCA and the iris ceased dendritic growth early in postnatal development, whereas the dendritic complexity of neurons supplying the SMG increased well into adulthood. By contrast, dendritic atrophy was seen in aged MCA- and SMG-projecting neurons but not in those innervating the iris, suggesting, with other evidence, correlated and distinct patterns of growth and atrophy in axons and dendrites of mature sympathetic neurons projecting to different targets. Swollen dendrites and protuberances on cell soma were a prominent feature of aged neurons. In addition to the target-specific variation in neuronal morphology, we observed diversity in neurotransmitter phenotype. For example, neuropeptide Y was expressed in iridial but not SMG-projecting neurons. These results show a range of age- and target-specific differences in the dendritic morphology and neuropeptide content of sympathetic neurons that may be a result of differing trophic interactions with their target tissues.

Aging↗