scholarly journals Modelling transport and mean age of dense core vesicles in large axonal arbours

2019 ◽  
Vol 475 (2228) ◽  
pp. 20190284
Author(s):  
I. A. Kuznetsov ◽  
A. V. Kuznetsov
Keyword(s):  
Steady State ◽  
Dense Core ◽  
Type Ii ◽  
Dense Core Vesicles ◽  
Density Distributions ◽  
The Mean

A model simulating the transport of dense core vesicles (DCVs) in type II axonal terminals of Drosophila motoneurons has been developed. The morphology of type II terminals is characterized by the large number of en passant boutons. The lack of both scaled-up DCV transport and scaled-down DCV capture in boutons results in a less efficient supply of DCVs to distal boutons. Furthermore, the large number of boutons that DCVs pass as they move anterogradely until they reach the most distal bouton may lead to the capture of a majority of DCVs before they turn around in the most distal bouton to move in the retrograde direction. This may lead to a reduced retrograde flux of DCVs and a lack of DCV circulation in type II terminals. The developed model simulates DCV concentrations in boutons, DCV fluxes between the boutons, age density distributions of DCVs and the mean age of DCVs in various boutons. Unlike published experimental observations, our model predicts DCV circulation in type II terminals after these terminals are filled to saturation. This disagreement is likely because experimentally observed terminals were not at steady state, but rather were accumulating DCVs for later release. Our estimates show that the number of DCVs in the transiting state is much smaller than that in the resident state. DCVs travelling in the axon, rather than DCVs transiting in the terminal, may provide a reserve of DCVs for replenishing boutons after a release. The techniques for modelling transport of DCVs developed in our paper can be used to model the transport of other organelles in axons.

scholarly journals How old are dense-core vesicles residing in en passant boutons: simulation of the mean age of dense-core vesicles in axonal arbours accounting for resident and transiting vesicle populations

2020 ◽  
Vol 476 (2241) ◽  
pp. 20200454
Author(s):  
Ivan A. Kuznetsov ◽  
Andrey V. Kuznetsov
Keyword(s):  
Dopaminergic Neurons ◽  
Axon Terminal ◽  
Axonal Degeneration ◽  
Dense Core ◽  
Age Difference ◽  
Type Ii ◽  
Dense Core Vesicles ◽  
Axon Terminals ◽  
The Mean ◽  
Dying Back

In neurons, neuropeptides are synthesized in the soma and are then transported along the axon in dense-core vesicles (DCVs). DCVs are captured in varicosities located along the axon terminal called en passant boutons, which are active terminal sites that accumulate and release neurotransmitters. Recently developed experimental techniques allow for the estimation of the age of DCVs in various locations in the axon terminal. Accurate simulation of the mean age of DCVs in boutons requires the development of a model that would account for resident, transiting-anterograde and transiting-retrograde DCV populations. In this paper, such a model is developed. The model is applied to simulating DCV transport in Drosophila type II motoneurons. The model simulates DCV transport and capture in the axon terminals and makes it possible to predict the age density distribution of DCVs in en passant boutons as well as DCV mean age in boutons. The predicted prevalence of older organelles in distal boutons may explain the ‘dying back’ pattern of axonal degeneration observed in dopaminergic neurons in Parkinson's disease. The predicted difference of two hours between the age of older DCVs residing in distal boutons and the age of younger DCVs residing in proximal boutons is consistent with an approximate estimate of age difference deduced from experimental observations. The age density of resident DCVs is found to be bimodal, which is because DCVs are captured from two transiting states: the anterograde transiting state that contains younger DCVs and the retrograde transiting state that contains older DCVs.

scholarly journals Simulating Reversibility of Dense Core Vesicles Capture in En Passant Boutons: Using Mathematical Modeling to Understand the Fate of Dense Core Vesicles in En Passant Boutons

2018 ◽  
Vol 140 (5) ◽  
Author(s):  
I. A. Kuznetsov ◽  
A. V. Kuznetsov
Keyword(s):  
Mathematical Modeling ◽  
Steady State ◽  
Nerve Terminal ◽  
Dense Core ◽  
Reasonable Assumption ◽  
Nerve Terminals ◽  
Dense Core Vesicles ◽  
Type Iii ◽  
Capture And Release ◽  
Kinetics Of

The goal of this paper is to use mathematical modeling to investigate the fate of dense core vesicles (DCVs) captured in en passant boutons located in nerve terminals. One possibility is that all DCVs captured in boutons are destroyed, another possibility is that captured DCVs can escape and reenter the pool of transiting DCVs that move through the boutons, and a third possibility is that some DCVs are destroyed in boutons, while some reenter the transiting pool. We developed a model by applying the conservation of DCVs in various compartments composing the terminal, to predict different scenarios that emerge from the above assumptions about the fate of DCVs captured in boutons. We simulated DCV transport in type Ib and type III terminals. The simulations demonstrate that, if no DCV destruction in boutons is assumed and all captured DCVs reenter the transiting pool, the DCV fluxes evolve to a uniform circulation in a type Ib terminal at steady-state and the DCV flux remains constant from bouton to bouton. Because at steady-state the amount of captured DCVs is equal to the amount of DCVs that reenter the transiting pool, no decay of DCV fluxes occurs. In a type III terminal at steady-state, the anterograde DCV fluxes decay from bouton to bouton, while retrograde fluxes increase. This is explained by a larger capture efficiency of anterogradely moving DCVs than of retrogradely moving DCVs in type III boutons, while the captured DCVs that reenter the transiting pool are assumed to be equally split between anterogradely and retrogradely moving components. At steady-state, the physiologically reasonable assumption of no DCV destruction in boutons results in the same number of DCVs entering and leaving a nerve terminal. Because published experimental results indicate no DCV circulation in type III terminals, modeling results suggest that DCV transport in these type III terminals may not be at steady-state. To better understand the kinetics of DCV capture and release, future experiments in type III terminals at different times after DCV release (molting) may be proposed.

scholarly journals Simulation of a sudden drop-off in distal dense core vesicle concentration in Drosophila type II motoneuron terminals

2021 ◽  
Author(s):  
Ivan A Kuznetsov ◽  
Andrey V Kuznetsov
Keyword(s):  
Molecular Motors ◽  
Synaptic Function ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Type Ii ◽  
Dense Core Vesicles ◽  
Sudden Drop

This paper aims to investigate whether the sudden drop in the content of dense core vesicles (DCVs) reported in [J. Tao, D. Bulgari, D.L. Deitcher, E.S. Levitan, Limited distal organelles and synaptic function in extensive monoaminergic innervation, J. Cell. Sci. 130 (2017) 2520-2529] can be explained without modifying the parameters characterizing the ability of distal en passant boutons to capture and accumulate DCVs. We hypothesize that the drop in DCV content in distal boutons is due to an insufficient supply of anterogradely moving DCVs coming from the soma. As anterogradely moving DCVs are captured (and eventually destroyed) in more proximal boutons on their way to the end of the terminal, the fluxes of anterogradely moving DCVs between the boutons become increasingly smaller, and the most distal boutons are left without DCVs. We tested this hypothesis by modifying the flux of DCVs entering the terminal and found that the number of most distal boutons left unfilled increases if the DCV flux entering the terminal is decreased. The number of anterogradely moving DCVs in the axon can be increased either by the release of a portion of captured DCVs into the anterograde component or by an increase of the anterograde DCV flux into the terminal. This increase could lead to having enough anterogradely moving DCVs such that they could reach the most distal bouton and then turn around by changing molecular motors that propel them. The model suggests that this could result in an increased concentration of resident DCVs in distal boutons beginning with bouton 2. This is because in distal boutons, DCVs have a larger chance to be captured from the transiting state as they pass the boutons moving anterogradely and then again as they pass the same boutons moving retrogradely.

Relationship between golgi apparatus and axonal reticulum in sympathetic ganglion cells

1978 ◽  
Vol 36 (2) ◽  
pp. 598-599
Author(s):  
J. Quatacker ◽  
W. De Potter
Keyword(s):  
Golgi Apparatus ◽  
Sympathetic Ganglion ◽  
Phosphotungstic Acid ◽  
Ganglion Cells ◽  
Low Ph ◽  
Dense Core ◽  
Dense Core Vesicles ◽  
Large Dense Core Vesicles ◽  
Cervical Ganglia ◽  
Axoplasmic Reticulum

Mucopolysaccharides have been demonstrated biochemically in catecholamine-containing subcellular particles in different rat, cat and ox tissues. As catecholamine-containing granules seem to arise from the Golgi apparatus and some also from the axoplasmic reticulum we examined wether carbohydrate macromolecules could be detected in the small and large dense core vesicles and in structures related to them. To this purpose superior cervical ganglia and irises from rabbit and cat and coeliac ganglia and their axons from dog were subjected to the chromaffin reaction to show the distribution of catecholamine-containing granules. Some material was also embedded in glycolmethacrylate (GMA) and stained with phosphotungstic acid (PTA) at low pH for the detection of carbohydrate macromolecules.The chromaffin reaction in the perikarya reveals mainly large dense core vesicles, but in the axon hillock, the axons and the terminals, the small dense core vesicles are more prominent. In the axons the small granules are sometimes seen inside a reticular network (fig. 1).

The global dynamics of stochastic Holling type II predator-prey models with non constant mortality rate

Filomat ◽  
2017 ◽  
Vol 31 (18) ◽  
pp. 5811-5825
Author(s):  
Xinhong Zhang
Keyword(s):  
Mortality Rate ◽  
Stochastic Model ◽  
Sufficient Conditions ◽  
Positive Periodic Solution ◽  
Global Dynamics ◽  
Type Ii ◽  
Predator Prey ◽  
Persistence In The Mean ◽  
The Mean ◽  
Predator Prey Models

In this paper we study the global dynamics of stochastic predator-prey models with non constant mortality rate and Holling type II response. Concretely, we establish sufficient conditions for the extinction and persistence in the mean of autonomous stochastic model and obtain a critical value between them. Then by constructing appropriate Lyapunov functions, we prove that there is a nontrivial positive periodic solution to the non-autonomous stochastic model. Finally, numerical examples are introduced to illustrate the results developed.

Flow cytometric identification and isolation of hypertrophic type II pneumocytes after partial pneumonectomy

1989 ◽  
Vol 257 (3) ◽  
pp. C528-C536 ◽  
Author(s):  
B. D. Uhal ◽  
S. R. Rannels ◽  
D. E. Rannels
Keyword(s):  
Gradient Centrifugation ◽  
Type Ii Cells ◽  
Type Ii ◽  
Acridine Orange Staining ◽  
Flow Cytometric ◽  
Percoll Density Gradient Centrifugation ◽  
Type Ii Pneumocytes ◽  
The Mean ◽  
Cellular Dna ◽  
The Right

Type II pneumocytes were isolated by either Percoll density gradient centrifugation or by immunoglobulin G (IgG) panning from the lungs of normal rats and the right lung of rats subjected to left pneumonectomy. Cells were studied at 7- (pnx-7) and 15- (pnx-15) days postoperative, times during and after, respectively, rapid compensatory growth of the right lung. Acridine orange staining permitted resolution of type II cells from contaminants on the basis of high red fluorescence (greater than 590 nm). Simultaneous measurement of forward-angle light scatter (FALS) suggested a shift of pnx-7 cells toward greater size, which was reversed in pnx-15 cells. By Percoll gradient isolation, approximately 15% of pnx-7 cells analyzed were above the mean FALS of control cells. In contrast, approximately 30% of the pnx-7 cells isolated by IgG panning were above the mean FALS of corresponding control cells. Biochemical analyses of pnx-7 cells separated by cell sorting into "high FALS" and "low FALS" subgroups revealed that high FALS type II cells contained 50% more protein (P less than 0.05) and 140% more RNA (P less than 0.01) than low FALS cells, with no significant change in cellular DNA content. These data are consistent with previous studies of type II cells isolated from the lungs of pneumonectomized animals and confirm the presence of hypertrophic cells in these preparations. They provide a foundation from which to design further flow cytometric studies of the role of hypertrophic type II pneumocytes in compensatory lung growth.

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