scholarly journals Valproic Acid Accelerates Neural Outgrowth during Dorsal Root Ganglia Neurogenesis In Vitro

2019 ◽  
pp. 149-162
Author(s):  
Wiens D ◽  
Bergan H ◽  
Walter OS ◽  
McGinley A ◽  
Ahlrichs B
Keyword(s):  
Valproic Acid ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Trichostatin A ◽  
Time Lapse ◽  
Growth Cones ◽  
Autism Spectrum ◽  
Neuronal Structure ◽  
And Behavior

Background: Valproic acid (VPA) is an anti-convulsant drug used to treat seizures and a variety of neural pathologies. Studies have shown that VPA exposure in rodent embryos leads to behavioral characteristics similar to those in humans with autism spectrum disorder (ASD). Utilizing this rodent model of ASD, research has led to a recognized mechanism of action of VPA involving brain overgrowth and hyperconnectivity, likely caused by epigenetic alteration of gene expression through inhibition of histone deacetylases.Objective: To gain further insight concerning this mechanism we modeled the development of neural connectivity at the cellular level.Method: We cultured dorsal root ganglia (DRGs) taken from eight-day old chick embryos in a range of VPA concentrations and investigated aspects of neuronal structure and behavior. DRGs were cultured 48 hours, fixed, and immunostained to reveal the locations of neural networks with synaptic vesicles.Results: We found a concentration-dependant relationship with a significant increase in neurite length in VPA concentrations of 1 and 2 mM, and the effect was still present though weaker at 4 and 6 mM. Trichostatin A (TSA), another histone deacetylase inhibitor, caused similar responses. To further characterize the effects, we carried out time-lapse imaging of growth cones of extending neurites. We found that VPA increased the area changing activity of growth cones, augmenting their exploratory capabilities, along with significantly enhancing overall advancement, thus increasing the ability to extend and form synapses. The average total of stained synaptic areas surrounding each cultured DRG was significantly increased in 6 mM VPA, but not significantly at the lower concentrations compared to controls.Conclusion: Our results show that VPA, at 1 mM and higher concentrations increases growth cone activity, and increases the number of neurites and their extension, a neurotrophic effect. It also increases synaptogenesis at 6 mM, supporting the theory of developmental neuronal overgrowth.

Neurotoxicity of Seven MEIC Chemicals Evaluated in Organotypic Cultures of Chick Embryonic Dorsal Root Ganglia

1997 ◽  
Vol 25 (3) ◽  
pp. 303-309
Author(s):  
Václav Mandys ◽  
Katerina Jirsová ◽  
Jirí Vrana
Keyword(s):  
Toxic Effect ◽  
Neurite Outgrowth ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Growth Parameters ◽  
In Vitro Cytotoxicity ◽  
Organotypic Cultures ◽  
Response Curves ◽  
Agar Culture

The neurotoxic effects of seven selected Multicenter Evaluation of In Vitro Cytotoxicity programme chemicals (methanol, ethanol, isopropanol, sodium chloride, potassium chloride, iron [II] sulphate and chloroform) were evaluated in organotypic cultures of chick embryonic dorsal root ganglia (DRG), maintained in a soft agar culture medium. Two growth parameters of neurite outgrowth from the ganglia — the mean radial length of neurites and the area of neurite outgrowth — were used to evaluate the toxicities of the chemicals. Dose-dependent decreases of both parameters were observed in all experiments. IC50 values (the concentration causing 50% inhibition of growth) were calculated from the dose-response curves established at three time-points during culture, i.e. 24, 48 and 72 hours. The lowest toxic effect was observed in cultures exposed to methanol (the IC50 ranging from 580mM to 1020mM). The highest toxic effect was observed in cultures exposed to iron (II) sulphate (the IC50 ranging from 1.2mM to 1.7mM). The results of other recent experiments suggest that organotypic cultures of DRG can be used during in vitro studies on target organ toxicity within the peripheral nervous system. Moreover, these cultures preserve the internal organisation of the tissue, maintain intercellular contacts, and thus reflect the in vitro situation, more precisely than other cell cultures.

Axon repulsion during peripheral nerve segmentation

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 131-139 ◽  
Author(s):  
Roger J. Keynes ◽  
Karen F. Jaques ◽  
Geoffrey M. W. Cook
Keyword(s):  
Dorsal Root ◽  
Grey Matter ◽  
Growth Cones ◽  
Spinal Nerve ◽  
Chick Embryos ◽  
Posterior Half ◽  
Similar Activity ◽  
Sensory Axons ◽  
Axon Repulsion

The guidance of axons during embryonic development is likely to involve both adhesive and repulsive interactions between growth cones and their environment. We are characterising the role and mechanism of repulsion during the segmental outgrowth of motor and sensory axons in the somite mesoderm of chick embryos. Axons are confined to the anterior half of each somite by the expression in the posterior half of a glycoconjugate system (48×103Mr and 55×103Mr) that causes the collapse of dorsal root ganglion growth cones when applied in vitro. Enzymatic cleavage of this fraction with specific combinations of endo- and exoglycosidases removes collapse activity, suggesting that carbohydrate residues are involved in the execution of collapse. A similar activity is also detectable in normal adult grey matter, suggesting roles for repulsion beyond the development of spinal nerve segmentation.

Dorsal root ganglia cocultured with macrophages: an in vitro model to study experimental demyelination

1994 ◽  
Vol 88 (5) ◽  
pp. 459-464 ◽  
Author(s):  
W. Br�ck ◽  
Y. Br�ck ◽  
U. Diederich ◽  
R. L. Friede
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
In Vitro Model ◽  
Experimental Demyelination ◽  
Vitro Model

An improved method for in vitro morphofunctional analysis of mouse dorsal root ganglia

2016 ◽  
Vol 207 ◽  
pp. 62-67 ◽  
Author(s):  
E. Ciglieri ◽  
F. Ferrini ◽  
E. Boggio ◽  
C. Salio
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Improved Method ◽  
Morphofunctional Analysis

Analysis of high PSA N-CAM expression during mammalian spinal cord and peripheral nervous system development

Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 69-82 ◽  
Author(s):  
S. Boisseau ◽  
J. Nedelec ◽  
V. Poirier ◽  
G. Rougon ◽  
M. Simonneau
Keyword(s):  
Spinal Cord ◽  
Neural Crest ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Developmental Stages ◽  
System Development ◽  
Nervous System Development ◽  
Homogeneous Distribution ◽  
Total N

Using a monoclonal antibody that recognizes specifically a high polysialylated form of N-CAM (high PSA N-CAM), the temporal and spatial expression of this molecule was studied in developing spinal cord and neural crest derivatives of mouse truncal region. Temporal expression was analyzed on immunoblots of spinal cord and dorsal root ganglia (DRGs) extracts microdissected at different developmental stages. Analysis of the ratio of high PSA N-CAM to total N-CAM indicated that sialylation and desialylation are independently regulated from the expression of polypeptide chains of N-CAM. Motoneurons, dorsal root ganglia cells and commissural neurons present a homogeneous distribution of high PSA N-CAMs on both their cell bodies and their neurites. Sialylation of N-CAM can occur in neurons after their aggregation in peripheral ganglia as demonstrated for dorsal root ganglia at E12. Furthermore, peripheral ganglia express different levels of high PSA N-CAM. With in vitro models using mouse neural crest cells, we found that expression of high PSA N-CAM was restricted to cells presenting an early neuronal phenotype, suggesting a common regulation for the expression of high PSA N-CAM molecules, neurofilament proteins and sodium channels. Using perturbation experiments with endoneuraminidase, we confirmed that high PSA N-CAM molecules are involved in fasciculation and neuritic growth when neurons derived from neural crest grow on collagen substrata. However, we demonstrated that these two parameters do not appear to depend on high PSA N-CAM molecules when cells were grown on a fibronectin substratum, indicating the existence of a hierarchy among adhesion molecules.

Neuronal intermediate filament expression in rat dorsal root ganglia sensory neurons: An in vivo and in vitro study

Neuroscience ◽  
2008 ◽  
Vol 153 (4) ◽  
pp. 1153-1163 ◽  
Author(s):  
M. Fornaro ◽  
J.M. Lee ◽  
S. Raimondo ◽  
S. Nicolino ◽  
S. Geuna ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Intermediate Filament ◽  
Dorsal Root ◽  
In Vitro Study ◽  
Vitro Study

Blockage of lysophosphatidic acid reverses arthritis-induced hypersensitivity and Cavα2δ1 and P2X3 expression in dorsal root ganglia

2015 ◽  
Vol 8 (1) ◽  
pp. 53-54 ◽  
Author(s):  
J. Su ◽  
A. Delaney ◽  
R. Matteo ◽  
B. Bartlett ◽  
K. Kultima ◽  
...  
Keyword(s):  
Dorsal Root Ganglia ◽  
Lysophosphatidic Acid ◽  
Dorsal Root ◽  
Thermal Sensitivity ◽  
Clinical Signs ◽  
Bone Cancer Pain ◽  
Mrna Levels ◽  
Mice Model ◽  
Antibody Treatment

AbstractAimsThe lysophosphatidic acid (LPA) is an important mediator involved in neuropathic and bone cancer pain models. We are investigating if LPA is involved in arthritis-induced pain in the collagen antibody-induced arthritis (CAIA) mice model.MethodsArthritis was induced in male CBA mice by injection of 1.5 mg collagen type II antibody cocktail. Mechanical and thermal sensitivity and the degree of arthritis were assessed with von Frey filaments, Hargreaves box (heat), acetone test (cold) and visual scoring, respectively. LPA antibody and control IgG (10mg/kg), or saline was injected s.c. twice a week from day 12 through day 47. qPCR and immunohistochemical studies were undertaken in dorsal root ganglia (DRGs) to explore the expression of pain-related ion channels.ResultsAdministration of LPA antibody treatment reversed CAIA-induced mechanical and thermal hypersensitivity (p < 0.05) while had no effect on the early clinical signs of arthritis (p > 0.05). mRNA levels for the LPA synthesizing enzyme autotaxin were elevated in the CAIA group. On day 48, expression of the voltage-gated calcium channel Cavα2δ1 and the ATP-gated P2X3 receptor were significantly increased in the CAIA DRGs, which were completely prevented by LPA antibody treatment. Of note, based on in vitro experiment, LPA stimulation upregulated Cavα2δ1 and P2X3 expression in primary adult mouse DRG cultures.ConclusionsBlocking the action of systemic LPA reverses arthritis-induced hypersensitivity, potentially through regulation of Cavα2δ1 and P2X3 expression in peripheral neurons. Thus, our data point to that LPA may serve as a target for providing pain relief in arthritis.

In vitro studies of dissociated cells from newborn mouse dorsal root ganglia

1973 ◽  
Vol 54 ◽  
pp. 51-63 ◽  
Author(s):  
Silvio Varon ◽  
Charles Raiborn ◽  
Edward Tyszka
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
In Vitro Studies ◽  
Newborn Mouse ◽  
Dissociated Cells
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