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Viscerotopic Representation of the Alimentary Tract in the Dorsal and Ventral Vagal Complexes in the Rat
Published in Sue Ritter, Robert C. Ritter, Charles D. Barnes, Neuroanatomy and Physiology of Abdominal Vagal Afferents, 2020
S.M. Altschuler, L. Rinaman, R.R. Miselis
Over the last decade, our laboratory has studied the viscerotopic organization of the NA, NTS, and DMN in the rat using a sensitive retrograde and antegrade tracer, cholera toxin horseradish peroxidase (CT-HRP). This tracer, which we prepare in our lab (see Altschuler et al.4 for detailed methods of synthesis) is created by the covalent conjugation of HRP to CT. We have found this tracer to be more effective than free HRP and equally effective to the wheat germ agglutinin conjugate of HRP in labeling afferent terminal fields.1,4,83 Additionally, this tracer is especially effective in labeling distal dendritic processes of retrogradely labeled neurons.3,4,7,69,70,83 The superior labeling seen with this tracer is derived from its ligand affinities for the superficial carbohydrate residues (GM1 gangliosides) of plasma membranes and intracellular transport mechanisms.
Sanfilippo disease/mucopolysaccharidosis type III
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Patients with this disorder accumulate gangliosides in the brain [34, 35] including Gm2 and Gm3 [34], or there may increased amounts of Gm1 [35]. The electron microscopic appearance of the neurons may be like those of Tay-Sachs disease [34] (Chapter 88). There may also be zebra bodies, and mucopolysaccharide may accumulate in the brain, as well as in the peripheral tissues.
Nasopharyngeal and oral immune system
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Hiroshi Kiyono, Kohtaro Fujihashi
The olfactory neuroepithelium in the nasopharynx of mice constitutes approximately 50% of the nasal surface and has direct neuronal connections to the olfactory bulbs in the central nervous system (CNS). Consequently, a major safety concern in using mucosal adjuvants with nasal vaccination is that the adjuvant may enter and/or target olfactory neurons, bypassing the blood-brain barrier to gain access to olfactory bulbs and deeper structures in the brain parenchyma. Studies with enterotoxin adjuvants and more recently a recombinant adenovirus vector suggest that this adverse effect is in large part mediated by the ADP-ribosyl transferase activity via the targeted cellular receptors. Both nCT and nLTH-1 bind to GM1 on epithelial cells and require endocytosis followed by transport across the epithelial cell to reach the basolateral membrane. GM1 gangliosides also are abundantly expressed by cells of the CNS, and their concentration on neuronal and microglial cells varies during the development of various cell types and different regions of the brain. GM1 also is thought to play a role in cell-to-cell and cell-matrix interactions and may act synergistically with several growth factors in development. GM1 ligation did not generate a calcium flux following exposure of microglial cells to CT-B; however, binding of CT-B to cerebellar granule cells in vitro improved survival and was associated with intracellular calcium increases through L-type voltage-sensitive channels during the first 7 days of culture with reduced calcium fluxes later in culture.
Spinal cord injury – assessing tolerability and use of combined rehabilitation and NeuroAiD (SATURN) study – primary results of an exploratory study
Published in The Journal of Spinal Cord Medicine, 2023
Ramesh Kumar, Ohnmar Htwe, Azmi Baharudin, Shaharuddin Abdul Rhani, Kamalnizat Ibrahim, Jagdeep Singh Nanra, Muhindra Gsangaya, Hezery Harun, Khairrudin Kandar, Maatharasi Balan, Shawn Peh, Yogesh Pokharkar, Abhinay Ingole, Mohammad Hisam Ariffin
Spinal cord injury (SCI) leads to devastating consequences of severe neurological and functional deficits. It impacts the quality of life for survivors and their families with the lifetime cost of care ranging from $1.2 to more than $5.1 million per patient.1,2 SCI produces a cascade of deleterious processes which causes an accumulation of glutamate in the extracellular compartment and excitotoxicity of neighboring neurons, processes on which MLC601/MLC901 have shown their neuroprotective effect. There are currently no proven pharmacological therapies to augment motor function and functional recovery in SCI. Few pharmacologic therapies for SCI, among which are methylprednisolone, which have shown limited benefit/risk ratio with modest efficacy and possible severe complications,3 and monosialic ganglioside GM1 which did not show any significant sustained efficacy and possible severe complications.4
Genistein prevents the decrease in ganglioside levels induced by amyloid-beta in the frontal cortex of rats
Published in Neurological Research, 2022
Fernanda dos Santos Petry, Juliana Bender Hoppe, Caroline Peres Klein, Bernardo Gindri dos Santos, Régis Mateus Hözer, Christianne Gazzana Salbego, Vera Maria Treis Trindade
To further explore the effects of Aβ1-42 infusion and treatment with genistein on ganglioside species, we performed TLC to evaluate the profile of these glycosphingolipids. This methodology allowed the detection of the main gangliosides present in the central nervous system of adult rats: GM1, GD1a, GD1b, GT1b and GQ1b (Figure 1). Figure 2 displays the individual ganglioside species, as a percentage of the control, for the different experimental groups. There were significant reductions of GD1b (p < 0.05) and GQ1b (p < 0.05) in the frontal cortex of rats that received the Aβ infusion followed by oral administration of vehicle when compared with the Veh/Veh group. In contrast, administration of genistein in Aβ-injected rats induced a significant increase of both these gangliosides, to a value similar to the control, when compared with the Aβ/Veh group (p < 0.05). No significant differences were observed in these parameters when genistein was administered to vehicle-injected rats in comparison to Veh/Veh group (p > 0.05).
Emerging pharmacological strategies for the management of chemotherapy-induced peripheral neurotoxicity (CIPN), based on novel CIPN mechanisms
Published in Expert Review of Neurotherapeutics, 2020
Andreas A. Argyriou, Jordi Bruna, Susanna B. Park, Guido Cavaletti
Gangliosides are glycosphingolipids, composed of a ceramide base with an oligosaccharide chain to which one or more sialic acids are bound. These are ubiquitous in outer layer of cell plasma membrane components, and highly abundant in the nervous system. Research into ganglioside function originates decades earlier, showing that gangliosides, especially the Ganglioside-monosialic acid GM1, are involved in a wide variety of neurotrophic and neuroprotective processes [46]. The best characterized GM1 mechanism of action suggests that exogenously supplied GM1 inserts in the membrane and modulates the neurotrophin tyrosine kinase receptors, Trk A and B, promoting cellular survival [47]. However, it should not be disregarded that some cancer cells, including colon adenocarcinoma, also express Trk receptors.