Abstract
We investigated the expression of immunoreactivity (IR) for low- (p75) and high-affinity (trk proteins) neurotrophin-receptor proteins in adult human paravertebral-sympathetic ganglion neurons. Mouse monoclonal antibodies against the pan-neurotrophin-receptor p75, and rabbit polyclonal antibodies against specific epitopes of the intracytoplasmic domain on trk neurotrophin-receptor proteins were used in fresh unfixed and formaldehyde-fixed paraffin-embedded sympathetic ganglia. All adult human paravertebral-sympathetic neurons displayed trkA neurotrophin-receptor-like protein IR, 10% express trkC neurotrophin-receptor-like protein IR, 37–44% show p75 IR, and no IR was obtained for trkB neurotrophin-receptor-like protein. The intensity of immunostaining was independent of the neuron size. Labelling of non-neuronal tissues, especially blood-vessel walls, was observed for p75, trkA and trkC neurotrophin-receptor proteins. These results indicate that overlapping exists in the expression of p75 and trk neurotrophin-receptor proteins in adult human paravertebral-sympathetic neurons, and suggest that neurotrophins might act on these neurons.
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Anand P, Radge P, Mathias CJ, Springall DR, Ghatei MA, Naher-Noe M, Sharief M, Misra VP, Polak JM, Bloom SR, Thomas PK (1991) New autonomic and sensory neuropathy with loss of adrenergic sympathetic function and sensory neuropeptides. Lancet 337:1253–1254
Andrews TJ, Cowen T (1994) Nerve growth factor enhances the dendritic arborization of sympathetic ganglion cells undergoing atrophy in aged rats. J Neurocytol 23:234–241
Apfel SC, Arezzo JC, Browlee M, Federoff H, Kessler JA (1994) Nerve growth factor administration protects against experimental diabetic sensory neuropathy. Brain Res 634:7–12
Barbacid M (1993) Nerve growth factor: a tale of two receptors. Oncogene 8: 2033–2042
Barker PA, Lomen-Hoerth C, Gensch EM, Meakin SO, Glass DJ, Shooter EM (1993) Tissue-specific alternative splicing generates two isoforms of the trkA receptor. J Biol Chem 268:15150–15157
Bothwell M (1995) Functional interactions of neurotrophins and neurotrophin receptors. Annu Rev Neurosci 18: 223–253
Chao MV, Hempstead B L (1995) p75 and Trk: a two-receptor system. Trends Neurosci 18: 321–326
Crowley C, Spencer SD, Nishimura MC, Chen KS, Pitts-Meek S, Armanini MP, Ling LH, McMahon SB, Shelton DL, Levinson AD, Phillips HS (1994) Mice lacking nerve growth factor display peripheral loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons. Cell 76: 1001–1011
Davies AM, Minichiello L, Klein R (1995) Developmental changes in NT3 signalling via TrkA and TrkB in embryonic neurons. EMBO J 14:4482–4489
Di Marco E, Cutuli N, Guerra L, Cancedda R, De Luca M (1993) Molecular cloning of trkE, a novel trk-related putative tyrosine kinase receptor isolated from normal human keratinocytes and widely expressed by normal human tissues. J Biol Chem 268: 24290–24295
Dixon JE, McKinnon D (1994) Expression of the trk gene family of neurotrophins receptors in prevertebral sympathetic ganglia. Brain Res Dev Brain Res 77: 177–182
Donovan MJ, Hampstead BL, Horvath C, Chao MV, Schofield D (1993) Immunohistochemical localization of Trk receptor protein in pediatric small round blue cell tumors. Am J Pathol 143: 1560–1567
Ehrhard PB, Otten U (1994) Postnatal ontogeny of the neurotrophin receptors trk and trkB mRNA in rat sensory and sympathetic ganglia. Neurosci Lett 166: 207–210
Ernfors P, Lee FK, Kucera J, Jaenisch R (1994) Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell 77: 503–512
Escandon E, Soppter D, Rosenthal A, Mendoza-Ramirez J-L, Szönyi E, Burton LE, Henderson CE, Parada LF, Nikolics K (1994) Regulation of neurotrophin receptor expression during embryonic and postnatal development. J Neurosci 14: 2054–2068
Fariñas I, Jones KR, Backus C, Wang X-Y, Reichardt LF (1994) Severe sensory and sympathetic deficits in mice lacking neurotrophin-3. Nature 369: 658–661
Götz R, Köster R, Winkler C, Raulf F, Lottspeich F, Schartl M, Thoenen H (1994) Neurotrophin-6 is a new member of the nerve growth factor family. Nature 372: 266–269
Helweg R, Hartung HD (1990) Endogenous levels of nerve growth factor (NGF) are altered in experimental diabetes mellitus: a possible role for NGF in pathogenesis of diabetic neuropathy. J Neurosci Res 26: 258–267
Ibañez CF (1995) Neurotrophic factors: from structure-function studies to designing effective therapeutics. Trends Biol Technol 13: 217–227
Jelsma TN, Aguayo AJ (1994) Trophic factors. Curr Opin Neurobiol 4:717–725
Jones KR, Fariñas I, Backus C, Reichardt LF (1994) Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell 76: 989–999
Kashiba H, Noguchi K, Ueda Y, Senba E (1995) Coexpression of trk family members and low-affinity neurotrophins receptors in rat dorsal root ganglion neurons. Mol Brain Res 30: 158–164
Klein R (1994) Role of neurotrophins in mouse neuronal development. FASEB J 8: 738–744
Klein R, Parada LF, Coullier F, Barbacid M (1989) trkB, a novel tyrosine protein kinase receptor expressed during mouse neural development. EMBO J 8: 3701–3709
Klein R, Smeyne RJ, Wurst W, Long LK, Auerbach BA, Joyner AL, Barbacid M (1993) Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death. Cell 75: 113–122
Klein R, Silos-Santiago I, Smeyne RJ, Lira SA, Brambilla R, Bryant S, Zhang L, Snider WD, Barbacid M (1994) Disruption of the neurotrophin-3 receptor gene trkC eliminates Ia muscle afferents and results in abnormal movements. Nature 368: 249–251
Kondo M, Terada M, Shimizu D, Fujiwara T, Tabei R (1990) Morphometric study of the superior cervical and stellate ganglia of spontaneously hypertensive rats during the prehypertensive stage. Virchows Arch B Cell Pathol 58: 371–376
Korsching S (1993) The neurotrophic factor concept: a reexamination. J Neurosci 13: 2739–2748
Lamballe F, P Tapley, M Barbacid (1993) trkC encodes multiple neurotrophin-3 receptors with distinct biological properties and substrate specificities. EMBO J 12: 3083–3094
Lamballe F, Smeyne RJ, Barbacid M (1994) Developmental expression of trkC, the neurotrophin-3 receptor, in the mammalian nervous system. J Neurosci 14: 14–28
Lee K-F, Li E, Huber LJ, Landis SC, Sharpe AH, Chao MV, Jaenisch AH (1992) Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell 69: 737–749
Levi-Montalcini R (1987) The nerve growth factor 35 years later. Science 237: 1154–1162
Lindsay RM, Wiegand SJ, Altar CA, Stefano PS (1994) Neurotrophic factors: from molecule to man. Trends Neurosci 17: 182–190
Longo FM, Holtzman DM, Grimes ML, Mobley WC (1993) Nerve growth factor: actions in the peripheral and central nervous system. In: Loughlin SE, Fallon JH (eds) Neurotrophic factors. Academic Press, New York London, pp 209–256
Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM, Yancopoulos GD (1990) Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science 247: 1446–1451
McMahon SB, Armanini MR Ling LH, Phillips HS (1994) Expression and coexpression of Trk receptors in a subpopulation of adult primary sensory neurons projecting to identified peripheral targets. Neuron 12: 1161–1171
Meakin SO, Shooter EM (1992) The nerve growth factor family of receptors. Trends Neurosci 15: 323–331
Messina A, Bell C (1991) Are genetically hypertensive rats deficient in nerve growth factor. Neuroreport 2: 45–48
Rodríguez-Tebar A, Dechant G, Götz R, Barde Y-A (1992) Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor. EMBO J 11: 917–922
Schecterson LC, Bothwell M (1992) Novel roles for neurotrophins are suggested by BDNF and NT-3 mRNA expression in developing neurons. Neuron 9: 449–463
Schmidt RE, McAtee SJ, Plurad DA, Parvin CA, Cogswell BE, Roth KA (1988) Differential susceptibility of prevertebral and paravertebral sympathetic ganglia to experimental injury. Brain Res 460: 214–226
Schmidt RE, Chae HY, Parvin CA, Roth KA (1990) Neuroaxonal dystrophy in aging human sympathetic ganglia. Am J Pathol 136: 1327–1338
Schmidt RE, Plurad SB, Parvin CA, Roth KA (1993) Effect of di abetes and aging on human sympathetic autonomic ganglia. Am J Pathol 145: 143–153
Shelton DL, Sutherland J, Gripp J, Camerato T, Armanini MP, Phillips HS, Carroll K, Spencer SD, Levinson AD (1995) Human trks: molecular cloning, tissue distribution, and expression of extracellular domain inmunoadhesins. J Neurosci 15: 477–491
Smeyne RJ, Klein R, Schnapps A, Long LK, Bryant S, Lewin A, Lira SA, Barbacid M (1994) Severe sensory and sympathetic neuropathies in mices carrying a disrupted trk/NGF receptor gene. Nature 368: 246–249
Snider WD (1994) Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77: 627–638
Sobue G, Yasuda T, Mitsuma T, Pleasure D (1989) Nere growth factor receptor immunoreactivity in the neuronal perikarya of human sensory and sympathetic ganglia. Neurology 39: 937–941
Tessarollo L, Tsoulfas P, Martin-Zanca D, Gilbert DJ, Jenkins NA, Copeland NG, Parada LF (1993) trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues. Development 118: 463–475
Vega JA, Humara JM, Naves FJ, Esteban I, Del Valle ME (1994a) Immunoreactivity for phosphorylated 200-kDa neurofilament subunit is heterogeneously expressed in human sympathetic and primary sensory neurons. Anat Embryol 190: 453–459
Vega JA, Vázquez E, Naves FJ, Del Valle ME, Calzada B, Represa JJ (1994b) Immunohistochemical localization of the high-affinity NGF receptor (gp 140-trkA) in the adult human dorsal root and sympathetic ganglia and in the nerves and sensory corpuscles supplying digital skin. Anat Rec 240: 579–588
Yamamoto M, Sobue G, Mutoh T, Li M, Doyu M, Mitsuma T, Kimata K (1993) Gene expression of high- (p140trk) and low-affinity nerve growth factor receptor (LNGFR) in the adult and aged human peripheral nervous system. Neurosci Lett 158:39–43
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Garcia-Suarez, O., Naves, F.J., Del Valle, M.E. et al. Distribution of p75 and trk-neurotrophin receptor proteins in adult human sympathetic ganglia. Anat Embryol 193, 577–583 (1996). https://doi.org/10.1007/BF00187929
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DOI: https://doi.org/10.1007/BF00187929