Enhancement of aging rat laryngeal muscles with endogenous growth factor treatment

Stemple, Joseph C.; Andreatta, Richard D.; Seward, Tanya; Angadi, Vrushali; Dietrich, Maria; McMullen, Colleen A.

doi:10.14814/phy2.12798

Cited by 3 publications

(2 citation statements)

References 46 publications

(105 reference statements)

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“…The molar mass of NT-4 calculated from the amino acid composition is equal to 14 kDa. Contrary to other neurotrophins, NT-4 is expressed pervasively throughout the central nervous system, and the observed concentration of NT-4 in serum samples may reach 19 ± 10 pg/mL. − …”

Section: Introductionmentioning

confidence: 99%

Adsorption/Desorption Transition of Recombinant Human Neurotrophin 4: Physicochemical Characterization

Dąbkowska¹,

Adamczak

Barbasz

et al. 2017

Langmuir

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Bulk physicochemical properties of neurotrophin 4 (NT-4) in electrolyte solutions and its adsorption/desorption on/from mica surfaces have been studied using dynamic light scattering (DLS), microelectrophoresis, a solution depletion technique (enzyme-linked immunosorbent assay, ELISA), and AFM imaging. Our study presents a determination of the diffusion coefficient, hydrodynamic diameters, electrophoretic mobility, and isoelectric point of the NT-4 under various ionic strength and pH conditions. The size of the NT-4 homodimer for an ionic strength of 0.015 M was substantially independent of pH and equal to 5.1 nm. It has been found that the number of electrokinetic charges per NT-4 molecule was equal to zero for all studied ionic strengths at pH 8.1, which was identified as the isoelectric point (iep). The protein adsorption/desorption on/from mica surfaces was examined as a function of ionic strength and pH. The kinetics of neurotrophin adsorption/desorption were evaluated at pH 3.5, 7.4, and 11 by direct AFM imaging and the ELISA technique. A monotonic increase in the maximum coverage of adsorbed NT-4 molecules with ionic strength (up to 5.5 mg/m) was observed at pH 3.5. These results were interpreted in terms of the theoretical model postulating an irreversible adsorption of the protein governed by the random sequential adsorption (RSA). Our measurements revealed a significant role of ionic strength, pH, and electrolyte composition in the lateral electrostatic interactions among differently charged NT-4 molecules. The transition between adsorption/desorption processes is found for the region of high pH and low surface concentration of adsorbed neurotrophin molecules at constant ionic strength. Additionally, results presented in this work show that the adsorption behavior of neurotrophin molecules may be governed by intrasolvent electrostatic interactions yielding an aggregation process. Understanding polyvalent neurotrophin interactions may have an impact on the reversibility/irreversibility of adsorption, and hence they might be useful for obtaining well-ordered protein layers, targeting the future development of drug delivery systems for treating neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Adsorption/Desorption Transition of Recombinant Human Neurotrophin 4: Physicochemical Characterization

Dąbkowska¹,

Adamczak

Barbasz

et al. 2017

Langmuir

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“…Among NMJ related DEGs, 33 were significantly altered by the 8 day pharmacological denervation and restored by electrical stimulation on both the stimulated and unstimulated soleus muscle. Some of the down‐regulated DEGs in the D8 controls groups were upregulated in response to electrical stimulation, that is, genes involved in the regulation of voltage‐gated potassium channels, neuronal growth regulation and cell survival (Lgi1), 22 muscle innervation and NMJ differentiation (Ntf4), 23 NMJ function, maturation and stabilization (Ky), 24 regulation of nerve homeostasis (P2rx6), 25 regulation of MuSK signalling (Pdzm3), motor axon guidance and extension (Slit1), 26 neuron outgrowth, cell adhesion and signalling (Lamb2), 27 regulation of axonal growth and growth (Mapk8ip1), 28 and NMJ formation (Apbb1) 29 . The decreased expression of these genes confirms the dysfunctions of NMJ in response to post‐synaptic blockade of neuromuscular transmission and the restoring effect of electrical stimulation.…”

Section: Discussionmentioning

confidence: 99%

Direct electrical stimulation impacts on neuromuscular junction morphology on both stimulated and unstimulated contralateral soleus

Lee

Cacciani

Wen

et al. 2023

J cachexia sarcopenia muscle

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Background There is increasing evidence of crosstalk between organs. The neuromuscular junction (NMJ) is a peripheral chemical synapse whose function and morphology are sensitive to acetylcholine (ACh) release and muscle depolarization. In an attempt to improve our understanding of NMJ plasticity and muscle crosstalk, the effects of unilateral direct electrical stimulation of a hindlimb muscle on the NMJ were investigated in rats exposed long-term post-synaptic neuromuscular blockade. Methods Sprague Dawley rats were subjected to post-synaptic blockade of neuromuscular transmission by systemic administration of α-cobrotoxin and mechanically ventilated for up to 8 days and compared with untreated sham operated controls and animals exposed to unilateral chronic electrical stimulation 12 h/day for 5 or 8 days. Results NMJs produced axonal and glial sprouts (growth of processes that extend beyond the confines of the synapse defined by high-density aggregates of acetylcholine receptors [AChRs]) in response to post-synaptic neuromuscular blockade, but less than reported after peripheral denervation or pre-synaptic blockade. Direct electrical soleus muscle stimulation reduced the terminal Schwann cell (tSC) and axonal sprouting in both stimulated and non-stimulated contralateral soleus. Eight days chronic stimulation reduced (P < 0.001) the number of tSC sprouts on stimulated and non-stimulated soleus from 6.7 ± 0.5 and 6.9 ± 0.5 sprouts per NMJ, respectively, compared with 10.3 ± 0.9 tSC per NMJ (P < 0.001) in non-stimulated soleus from rats immobilized for 8 days. A similar reduction of axonal sprouts (P < 0.001) was observed in stimulated and non-stimulated contralateral soleus in response to chronic electrical stimulation. RNAseq-based gene expression analyses confirmed a restoring effect on both stimulated and unstimulated contralateral muscle. The cross-over effect was paralleled by increased cytokine/chemokine levels in stimulated and contralateral unstimulated muscle as well as in plasma. Conclusions Motor axon terminals and terminal Schwann cells at NMJs of rats subjected to post-synaptic neuromuscular blockade exhibited sprouting responses. These axonal and glial responses were likely dampened by a muscle-derived myokines released in an activity-dependent manner with both local and systemic effects.

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Subcutaneous Neurotrophin 4 Infusion Using Osmotic Pumps or Direct Muscular Injection Enhances Aging Rat Laryngeal Muscles

Andreatta

Stemple

Seward

et al. 2017

JoVE

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Laryngeal dysfunction in the elderly is a major cause of disability, from voice disorders to dysphagia and loss of airway protective reflexes. Few, if any, therapies exist that target age-related laryngeal muscle dysfunction. Neurotrophins are involved in muscle innervation and differentiation of neuromuscular junctions (NMJs). It is thought that neurotrophins enhance neuromuscular transmission by increasing neurotransmitter release. The neuromuscular junctions (NMJs) become smaller and less abundant in aging rat laryngeal muscles, with evidence of functional denervation. We explored the effects of NTF4 for future clinical use as a therapeutic to improve function in aging human laryngeal muscles. Here, we provide the detailed protocol for systemic application and direct injection of NTF4 to investigate the ability of aging rat laryngeal muscle to remodel in response to NTF4 application. In this method, rats either received NTF4 either systemically via osmotic pump or by direct injection through the vocal folds. Laryngeal muscles were then dissected and used for histological examination of morphology and age-related denervation.

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Enhancement of aging rat laryngeal muscles with endogenous growth factor treatment

Cited by 3 publications

References 46 publications

Adsorption/Desorption Transition of Recombinant Human Neurotrophin 4: Physicochemical Characterization

Adsorption/Desorption Transition of Recombinant Human Neurotrophin 4: Physicochemical Characterization

Direct electrical stimulation impacts on neuromuscular junction morphology on both stimulated and unstimulated contralateral soleus

Subcutaneous Neurotrophin 4 Infusion Using Osmotic Pumps or Direct Muscular Injection Enhances Aging Rat Laryngeal Muscles

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