Calbindin‐immunoreactive sensory neurons of dorsal root ganglion project to skeletal muscle in the chick

Philippe, E

doi:10.1002/cne.902830113

Cited by 29 publications

(11 citation statements)

References 18 publications

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“…The WGA-dextran-magnetite experiments in rabbits confirm other reports [32] that particles of 5-15 nm are endocytosed and transported by intact nerve endings. Some studies have suggested that nerve injury is required for the transport of larger particles [33], but this result suggests that intact neurons will indeed transport large (up to 15 nm) multi-molecular aggregates or "transport particles" after intramuscular injection when the particles are well solvated.…”

Section: Resultssupporting

confidence: 89%

Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

et al. 2010

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BackgroundTargeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior.ResultsWe developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle.ConclusionSpecific targeting of selected subpopulations of CNS neurons for drug delivery by axonal transport holds great promise. The data shown here provide a basic framework for the intraneural pharmacology of this tripartite complex. The pharmacologically efficacious drug delivery demonstrated here verify the fundamental feasibility of using axonal transport for targeted drug delivery.

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Section: Resultssupporting

confidence: 89%

Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

et al. 2010

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“…CB has been reported to act not only as a passive store but also to have an active role in neuronal activity due to its high Ca 2+ -binding activity (Baimbridge et al 1992). In DRG, CB has predominantly been found in large-sized neurons whose peripheral terminals innervate muscle spindles (Philippe and Droz 1989). It has also been found in a subpopulation of medium-or small-sized muscle and visceral nociceptors (Honda 1995).…”

Section: Discussionmentioning

confidence: 99%

Tetrodotoxin induced changes in the chemical coding of dorsal root ganglion neurons supplying the porcine urinary bladder

Bossowska¹,

Majewski²

2012

Polish Journal of Veterinary Sciences

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Tetrodotoxin (TTX) mode of action is based on a blocking of fast sodium channels in nerve cell membrane what, in turn, abolishes the propagation of the action potential along the nerve fibers. TTX is currently used in experimental therapies focused on neoplastic or neurogenic pain, however, as for now there is no data concerning the influence of TTX on dorsal root ganglion (DRG) sensory neurons function. Thus, the present study was aimed at characterization of neurochemical coding of porcine sensory bladder-projecting cells after bladder instillation with TTX. Retrograde tracer Fast Blue (FB) was injected into the urinary bladder wall of six juvenile female pigs and three weeks later bladder instillation with TTX (12 μg per animal) was carried out in all animals. A week later, DRGs of interest were harvested from all animals and the neurochemical characterization of FB + neurons was performed using routine double-immunofluorescence labeling technique on 10-μm-thick cryostat sections. In TTX-treated animals the number of FB + cells containing galanin (GAL), nitric oxide synthase (NOS), somatostatin (SOM) and calbindin (CB) was 2.5%, 2%, 0.25% and 0.2%, respectively and that of pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive (IR) cells was 43%. These data when compared with previous reports, demonstrated that TTX profoundly changed the chemical coding of porcine bladder-projecting sensory neurons thus implicating that it may be used in case of hypoactivity of afferent part of reflex arc responsible for transmission of sensory information from the urinary bladder.

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“…Philippe and Droz, 1989, but see their Note Added in Proof). Expression of CALB was heterogeneous among TMN neurons, however.…”

Section: Markers Expressed In Tmn Neuronsmentioning

confidence: 92%

Cytochemical characteristics of neurons in the trigeminal mesencephalic nucleus of hatchling chicks

Scott

Dinowitz

Terhaar

et al. 1994

J of Comparative Neurology

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The goal of the present study was to identify cytochemical markers characteristic of muscle afferents in hatchling chicks. To this end, we stained neurons in the trigeminal mesencephalic nucleus with a variety of markers that label subsets of neurons in avian dorsal root ganglia. We found that trigeminal mesencephalic neurons are surprisingly heterogeneous in their cytochemical make-up, expressing, to varying degrees, substance P, cholecystokinin, carbonic anhydrase, calbindin D-28k, parvalbumin, and S-100 beta. Calbindin D28k and S-100 beta appeared to be expressed equally in medial and lateral divisions of the trigeminal mesencephalic nucleus. In contrast, substance P- and cholecystokinin-immunoreactive neurons were more abundant in the medial division, whereas carbonic anhydrase activity and parvalbumin immunoreactivity were stronger in the lateral division. We were unable to detect met-enkephalin, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal peptide, somatostatin, gamma-aminobutyric acid, or tyrosine hydroxylase in the trigeminal mesencephalic nucleus. Moreover, these neurons did not appear to bind the lectin Dolichos biflorus agglutinin. The heterogeneity of expression of markers among trigeminal mesencephalic nucleus neurons, especially between neurons in the medial and lateral divisions, suggests that these neurons are functionally diverse.

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Calbindin‐immunoreactive sensory neurons of dorsal root ganglion project to skeletal muscle in the chick

Cited by 29 publications

References 18 publications

Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

Tetrodotoxin induced changes in the chemical coding of dorsal root ganglion neurons supplying the porcine urinary bladder

Cytochemical characteristics of neurons in the trigeminal mesencephalic nucleus of hatchling chicks

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