The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform

Mirna Mustapha - One of the best experts on this subject based on the ideXlab platform.

  • thyroid hormone is required for the pruning of afferent type ii spiral ganglion neurons in the Mouse cochlea
    Neuroscience, 2016
    Co-Authors: Srividya Sundaresan, S Balasubbu, Mirna Mustapha
    Abstract:

    Abstract Afferent connections to the sensory inner (IHCs) and outer hair cells (OHCs) in the cochlea refine and functionally mature during the thyroid hormone (TH)-critical period of inner ear development that occurs perinatally in rodents. In this study, we investigated the effects of hypothyroidism on afferent type II innervation to outer hair cells using the Snell Dwarf Mouse (Pit1dw). Using a transgenic approach to specifically label type II spiral ganglion neurons (SGNs), we found that lack of TH causes persistence of excess type II SGN connections to the OHCs, as well as continued expression of the hair cell functional marker, otoferlin (OTOF), in the OHCs beyond the maturation period. We also observed a concurrent delay in efferent attachment to the OHCs. Supplementing with TH during the early postnatal period from postnatal day (P) 3 to P4 reversed the defect in type II SGN pruning but did not alter OTOF expression. Our results show that hypothyroidism causes a defect in the large-scale pruning of afferent type II SGNs in the cochlea, and a delay in efferent attachment and the maturation of OTOF expression. Our data suggest that the state of maturation of hair cells, as determined by OTOF expression, may not regulate the pruning of their afferent innervation.

  • Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses.
    European Journal of Neuroscience, 2015
    Co-Authors: Srividya Sundaresan, Jee-hyun Kong, Qing Fang, Felipe T. Salles, Felix Wangsawihardja, Anthony J. Ricci, Mirna Mustapha
    Abstract:

    Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell Dwarf Mouse (Pit1dw) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1dw mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1dw IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1dw IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1dw IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses.

John Papaconstantinou - One of the best experts on this subject based on the ideXlab platform.

  • akt pkb and p38 mapk signaling translational initiation and longevity in Snell Dwarf Mouse livers
    Mechanisms of Ageing and Development, 2004
    Co-Authors: Ching-chyuan Hsieh, John Papaconstantinou
    Abstract:

    The insulin/IGF-1/GH and p38 MAPK signaling pathways play a key role in the regulation of protein synthesis. The regulation of GH and TSH secretion hormones, that affect the activity of these pathways, plays an important role in the decline of rates of protein synthesis in aged rodent tissues. Studies have indicated that longevity of the Snell Dwarf (Pit-1) Mouse mutant is associated with the reduction of function of the insulin/IGF-1/GH signaling pathway. We have previously shown that PI3K activity, a signaling protein that plays a key role in the regulation of translation, is also dramatically decreased in the Snell Dwarf liver suggesting that the protein synthesis-signaling pathway may be attenuated in this long-lived Mouse. Similarly, signaling via p38 MAPK also plays a role in the regulation of protein synthesis. In this study we examined the activities of these signaling pathways to determine if the translation-signaling pathway is altered in young versus aged Snell Dwarf Mouse livers. Our data indicate that the phosphorylation and kinase activities of Akt/PKB and p38 MAPK, and the levels of phosphorylation of downstream regulators of translation are decreased in Dwarf Mouse livers. Thus, the overall activities of major components of the translational initiation pathway are decreased in the long-lived Snell Dwarf Mouse livers. We propose that down-regulation of protein synthesis may be an important characteristic of the Pit-1 mutation and longevity of the Snell Dwarf Mouse.

  • effects of the pit1 mutation on the insulin signaling pathway implications on the longevity of the long lived Snell Dwarf Mouse
    Mechanisms of Ageing and Development, 2002
    Co-Authors: Ching-chyuan Hsieh, James H. Deford, Kevin Flurkey, David E. Harrison, John Papaconstantinou
    Abstract:

    Mutations in Caenorhabditis elegans and mice have identified candidate genes that increase their lifespan via hormonal signal transduction, i.e. the insulin/IGF-1-like pathway. In this study we propose that longevity of the Snell Dwarf (Pit1(dw)/Pit1(dw)) Mouse is associated with a decrease of the insulin/IGF-1 signaling pathway caused by the Pit1 mutation. We recently demonstrated that the growth hormone deficiency of the Dwarf Mouse alters circulating insulin levels, thereby resulting in a decreased activity of the insulin/IGF-1 signaling pathway, which is a determining factor in the increased nematode lifespan. The decreased activity of the insulin/IGF-1 signaling pathway is indicated by decrease of (a) IRS-two pool levels; (b) docking of p85 alpha to IRS-2; (c) docking of p 85 alpha to p110 alpha or p110 beta, and (d) IRS-2-associated PI3K activity. In this study we present data suggesting that the InR beta-IRS-1-PI3K pathway is attenuated in the Snell Dwarf Mouse liver. Our data show that the PI3K activity associated with IRS-1, the docking of IRS-1 to InR beta and the docking of p85 alpha to IRS-1 are attenuated in the aged Snell Dwarf. Our studies suggest that the Pit1 mutation results in a decreased activity of the insulin/IGF-1 pathway; that this plays a key role in the longevity of the Snell Dwarf Mouse and conforms to the nematode longevity paradigm.

Srividya Sundaresan - One of the best experts on this subject based on the ideXlab platform.

  • thyroid hormone is required for the pruning of afferent type ii spiral ganglion neurons in the Mouse cochlea
    Neuroscience, 2016
    Co-Authors: Srividya Sundaresan, S Balasubbu, Mirna Mustapha
    Abstract:

    Abstract Afferent connections to the sensory inner (IHCs) and outer hair cells (OHCs) in the cochlea refine and functionally mature during the thyroid hormone (TH)-critical period of inner ear development that occurs perinatally in rodents. In this study, we investigated the effects of hypothyroidism on afferent type II innervation to outer hair cells using the Snell Dwarf Mouse (Pit1dw). Using a transgenic approach to specifically label type II spiral ganglion neurons (SGNs), we found that lack of TH causes persistence of excess type II SGN connections to the OHCs, as well as continued expression of the hair cell functional marker, otoferlin (OTOF), in the OHCs beyond the maturation period. We also observed a concurrent delay in efferent attachment to the OHCs. Supplementing with TH during the early postnatal period from postnatal day (P) 3 to P4 reversed the defect in type II SGN pruning but did not alter OTOF expression. Our results show that hypothyroidism causes a defect in the large-scale pruning of afferent type II SGNs in the cochlea, and a delay in efferent attachment and the maturation of OTOF expression. Our data suggest that the state of maturation of hair cells, as determined by OTOF expression, may not regulate the pruning of their afferent innervation.

  • Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses.
    European Journal of Neuroscience, 2015
    Co-Authors: Srividya Sundaresan, Jee-hyun Kong, Qing Fang, Felipe T. Salles, Felix Wangsawihardja, Anthony J. Ricci, Mirna Mustapha
    Abstract:

    Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell Dwarf Mouse (Pit1dw) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1dw mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1dw IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1dw IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1dw IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses.

Ching-chyuan Hsieh - One of the best experts on this subject based on the ideXlab platform.

  • akt pkb and p38 mapk signaling translational initiation and longevity in Snell Dwarf Mouse livers
    Mechanisms of Ageing and Development, 2004
    Co-Authors: Ching-chyuan Hsieh, John Papaconstantinou
    Abstract:

    The insulin/IGF-1/GH and p38 MAPK signaling pathways play a key role in the regulation of protein synthesis. The regulation of GH and TSH secretion hormones, that affect the activity of these pathways, plays an important role in the decline of rates of protein synthesis in aged rodent tissues. Studies have indicated that longevity of the Snell Dwarf (Pit-1) Mouse mutant is associated with the reduction of function of the insulin/IGF-1/GH signaling pathway. We have previously shown that PI3K activity, a signaling protein that plays a key role in the regulation of translation, is also dramatically decreased in the Snell Dwarf liver suggesting that the protein synthesis-signaling pathway may be attenuated in this long-lived Mouse. Similarly, signaling via p38 MAPK also plays a role in the regulation of protein synthesis. In this study we examined the activities of these signaling pathways to determine if the translation-signaling pathway is altered in young versus aged Snell Dwarf Mouse livers. Our data indicate that the phosphorylation and kinase activities of Akt/PKB and p38 MAPK, and the levels of phosphorylation of downstream regulators of translation are decreased in Dwarf Mouse livers. Thus, the overall activities of major components of the translational initiation pathway are decreased in the long-lived Snell Dwarf Mouse livers. We propose that down-regulation of protein synthesis may be an important characteristic of the Pit-1 mutation and longevity of the Snell Dwarf Mouse.

  • effects of the pit1 mutation on the insulin signaling pathway implications on the longevity of the long lived Snell Dwarf Mouse
    Mechanisms of Ageing and Development, 2002
    Co-Authors: Ching-chyuan Hsieh, James H. Deford, Kevin Flurkey, David E. Harrison, John Papaconstantinou
    Abstract:

    Mutations in Caenorhabditis elegans and mice have identified candidate genes that increase their lifespan via hormonal signal transduction, i.e. the insulin/IGF-1-like pathway. In this study we propose that longevity of the Snell Dwarf (Pit1(dw)/Pit1(dw)) Mouse is associated with a decrease of the insulin/IGF-1 signaling pathway caused by the Pit1 mutation. We recently demonstrated that the growth hormone deficiency of the Dwarf Mouse alters circulating insulin levels, thereby resulting in a decreased activity of the insulin/IGF-1 signaling pathway, which is a determining factor in the increased nematode lifespan. The decreased activity of the insulin/IGF-1 signaling pathway is indicated by decrease of (a) IRS-two pool levels; (b) docking of p85 alpha to IRS-2; (c) docking of p 85 alpha to p110 alpha or p110 beta, and (d) IRS-2-associated PI3K activity. In this study we present data suggesting that the InR beta-IRS-1-PI3K pathway is attenuated in the Snell Dwarf Mouse liver. Our data show that the PI3K activity associated with IRS-1, the docking of IRS-1 to InR beta and the docking of p85 alpha to IRS-1 are attenuated in the aged Snell Dwarf. Our studies suggest that the Pit1 mutation results in a decreased activity of the insulin/IGF-1 pathway; that this plays a key role in the longevity of the Snell Dwarf Mouse and conforms to the nematode longevity paradigm.

C M Sutton - One of the best experts on this subject based on the ideXlab platform.