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PMID: 7890832 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

TrkA-immunoreactive profiles in the central nervous system: colocalization with neurons containing p75 nerve growth factor receptor, choline acetyltransferase, and serotonin.

The Journal of comparative neurology ·Vol. 350 ·No. 4 ·1994-12-22 ·Pages 587-611

Sobreviela T, Clary DO, Reichardt LF, Brandabur MM, Kordower JH, Mufson EJ

Abstract

The present investigation used an antibody directed against the extracellular domain of the signal transducing nerve growth factor receptor, trkA, to reveal immunoreactive perikarya or fibers within the olfactory bulb and tubercle, cingulate cortex, nucleus accumbens, striatum, endopiriform nucleus, septal/diagonal band complex, nucleus basalis, hippocampal complex, thalamic paraventricular and reuniens nuclei, periventricular hypothalamus, interpeduncular nucleus, mesencephalic nucleus of the fifth nerve, dorsal nucleus of the lateral lemniscus, prepositus hypoglossal nucleus, ventral cochlear nucleus, ventral lateral tegmentum, medial vestibular nucleus, spinal trigeminal nucleus oralis, nucleus of the solitary tract, raphe nuclei, and spinal cord. Colocalization experiments revealed that virtually all striatal trkA-immunoreactive neurons (> 99%) coexpressed choline acetyltransferase (ChAT) but not p75 nerve growth factor receptor (NGFR). Within the septal/diagonal band complex virtually all trkA neurons (> 95%) coexpressed both ChAT and p75 NGFR. More caudally, dual stained sections revealed numerous trkA/ChAT (> 80%) and trkA/p75 NGFR (> 95%) immunoreactive neurons within the nucleus basalis. In the brainstem, raphe serotonergic neurons (45%) coexpressed trkA. Sections stained with a pan-trk antibody that recognizes primarily trkA, as well as trkB and trkC, labeled neurons within all of these regions as well as within the hypothalamic arcuate, supramammilary, and supraoptic nuclei, hippocampus, inferior and superior colliculus, substantia nigra, ventral tegmental area of T'sai, and cerebellular Purkinje cells. Virtually all of these other regions with the exception of the cerebellum also expressed pan-trk immunoreactivity in the monkey. The widespread expression of trkA throughout the central neural axis suggests that this receptor may play a role in signal transduction mechanisms linked to NGF-related substances in cholinergic basal forebrain and noncholinergic systems. These findings suggest that pharmacological use of ligands for trkA could have beneficial effects on the multiple neuronal systems that are affected in such disorders as Alzheimer's disease.

Related Genes
MeSH Terms
Animals Central Nervous System/cytology,enzymology Choline O-Acetyltransferase/metabolism Immunohistochemistry Male Nerve Fibers/enzymology Neurons/enzymology,metabolism Prosencephalon/enzymology,physiology Protein-Tyrosine Kinases/metabolism Raphe Nuclei/enzymology,physiology Rats Rats, Sprague-Dawley Receptors, Nerve Growth Factor/metabolism Serotonin/metabolism Signal Transduction/physiology
Chemicals
Receptors, Nerve Growth Factor Serotonin Choline O-Acetyltransferase Protein-Tyrosine Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sobreviela T
Department of Neurological Sciences, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
Clary D O
Reichardt L F
Brandabur M M
Kordower J H
Mufson E J
References (92)
92 references, click to expand
  1. The localization and distribution of high affinity beta-nerve growth factor binding sites in the central nervous system of the adult rat. A light microscopic autoradiographic study using [125I]beta-nerve growth factor.
    Neuroscience. 1987 Jan;20(1):23-36 PMID: 2436088
  2. NGF receptor gene expression is decreased in the nucleus basalis in Alzheimer's disease.
    Exp Neurol. 1989 Dec;106(3):222-36 PMID: 2556292
  3. Neurotrophins and their receptors--current concepts and implications for neurologic disease.
    Exp Neurol. 1993 Jun;121(2):200-14 PMID: 8339771
  4. Galanin immunoreactivity within the primate basal forebrain: evolutionary change between monkeys and apes.
    J Comp Neurol. 1993 Oct 1;336(1):31-9 PMID: 7504703
  5. K252a is a selective inhibitor of the tyrosine protein kinase activity of the trk family of oncogenes and neurotrophin receptors.
    Oncogene. 1992 Feb;7(2):371-81 PMID: 1312698
  6. Serotonergic projections to the spinal cord from the midbrain in the rat: an immunocytochemical and retrograde transport study.
    Neurosci Lett. 1981 Jul 17;24(3):221-6 PMID: 6168977
  7. Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family.
    Nature. 1990 Mar 22;344(6264):339-41 PMID: 2314473
  8. Grafting genetically modified cells to the damaged brain: restorative effects of NGF expression.
    Science. 1988 Dec 16;242(4885):1575-8 PMID: 3201248
  9. An immunohistochemical study of the nerve growth factor receptor in developing rats.
    J Neurosci. 1988 Sep;8(9):3481-98 PMID: 2845023
  10. Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system.
    Proc Natl Acad Sci U S A. 1986 Feb;83(3):817-21 PMID: 3456170
  11. Nerve growth factor (NGF) in the rat CNS: absence of specific retrograde axonal transport and tyrosine hydroxylase induction in locus coeruleus and substantia nigra.
    Brain Res. 1979 Jun 8;168(3):473-83 PMID: 86378
  12. Polymer-encapsulated cells genetically modified to secrete human nerve growth factor promote the survival of axotomized septal cholinergic neurons.
    Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2324-8 PMID: 8134395
  13. Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basalis in the rat.
    Brain Res. 1984 May 21;300(1):33-9 PMID: 6203605
  14. Physiology of nerve growth factor.
    Physiol Rev. 1980 Oct;60(4):1284-335 PMID: 6159658
  15. Antinociceptive effect of brain-derived neurotrophic factor and neurotrophin-3.
    Brain Res. 1994 Jan 7;633(1-2):326-30 PMID: 7511037
  16. Distribution of nerve growth factor receptor-like immunoreactivity in the adult rat central nervous system. Effect of colchicine and correlation with the cholinergic system--I. Forebrain.
    Neuroscience. 1990;34(1):57-87 PMID: 2158007
  17. Nerve growth factor receptor immunoreactivity within the nucleus basalis (Ch4) in Parkinson's disease: reduced cell numbers and co-localization with cholinergic neurons.
    Brain Res. 1991 Jan 18;539(1):19-30 PMID: 1849779
  18. Localization of nerve growth factor receptor messenger RNA and protein in the adult rat brain.
    Exp Neurol. 1989 Dec;106(3):209-21 PMID: 2556291
  19. Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkey.
    J Neurosci. 1990 Dec;10(12):3801-13 PMID: 2269884
  20. Neuronal colocalization of mRNAs for neurotrophins and their receptors in the developing central nervous system suggests a potential for autocrine interactions.
    Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6439-43 PMID: 8341652
  21. The localization of nerve growth factor-like immunoreactivity in the adult rat basal forebrain and hippocampal formation.
    J Comp Neurol. 1992 May 15;319(3):454-62 PMID: 1602053
  22. Nerve growth factor mediates signal transduction through trk homodimer receptors.
    Neuron. 1992 Dec;9(6):1067-79 PMID: 1281417
  23. Galaninergic innervation of the cholinergic vertical limb of the diagonal band (Ch2) and bed nucleus of the stria terminalis in aging, Alzheimer's disease and Down's syndrome.
    Dementia. 1993 Sep-Oct;4(5):237-50 PMID: 7505157
  24. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF.
    Science. 1990 Mar 23;247(4949 Pt 1):1446-51 PMID: 2321006
  25. High-affinity nerve growth factor receptor (Trk) immunoreactivity is localized in cholinergic neurons of the basal forebrain and striatum in the adult rat brain.
    Brain Res. 1993 May 28;612(1-2):330-5 PMID: 8330208
  26. NGF receptor (p75)-immunoreactivity in the developing primate basal ganglia.
    J Comp Neurol. 1993 Jan 15;327(3):359-75 PMID: 8440771
  27. Molecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system.
    Neuroscience. 1992 Dec;51(3):513-32 PMID: 1488112
  28. trk-immunoreactivity in the monkey central nervous system: forebrain.
    J Comp Neurol. 1994 Nov 1;349(1):20-35 PMID: 7852624
  29. Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells.
    Neuron. 1993 Feb;10(2):137-49 PMID: 7679912
  30. Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6).
    Neuroscience. 1983 Dec;10(4):1185-201 PMID: 6320048
  31. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB.
    Neuron. 1991 Nov;7(5):857-66 PMID: 1742028
  32. Effects of nerve crush and transection on mRNA levels for nerve growth factor receptor in the rat facial motoneurons.
    Brain Res Mol Brain Res. 1991 Jan;9(1-2):157-60 PMID: 1850072
  33. Gangliosides prevent the inhibition by K-252a of NGF responses in PC12 cells.
    Brain Res Dev Brain Res. 1992 Jan 17;65(1):35-42 PMID: 1551231
  34. Telencephalic cholinergic system of the New World monkey (Cebus apella): morphological and cytoarchitectonic assessment and analysis of the projection to the amygdala.
    J Comp Neurol. 1989 Jan 22;279(4):528-45 PMID: 2465322
  35. Expression of NGF and NGF receptor mRNAs in the developing brain: evidence for local delivery and action of NGF.
    Exp Neurol. 1989 Jun;104(3):191-9 PMID: 2542076
  36. Keeping track of neurotrophin receptors.
    Cell. 1991 Jun 14;65(6):915-8 PMID: 1646079
  37. Distribution of neuronal receptors for nerve growth factor in the rat.
    J Neurosci. 1986 Aug;6(8):2312-21 PMID: 3018191
  38. Expression of members of the trk family in the developing postnatal rat brain.
    Brain Res Dev Brain Res. 1993 Mar 19;72(1):119-31 PMID: 8453762
  39. Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection.
    Proc Natl Acad Sci U S A. 1986 Dec;83(23):9231-5 PMID: 3466184
  40. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family.
    Neuron. 1990 Oct;5(4):511-26 PMID: 2206535
  41. Recombinant human nerve growth factor infusions prevent cholinergic neuronal degeneration in the adult primate brain.
    Ann Neurol. 1991 Nov;30(5):625-36 PMID: 1763889
  42. Nerve growth factor receptor immunoreactivity in the new world monkey (Cebus apella) and human cerebellum.
    J Comp Neurol. 1991 Jun 22;308(4):555-75 PMID: 1650799
  43. Striatal degeneration induced by mitochondrial blockade is prevented by biologically delivered NGF.
    J Neurosci Res. 1993 Jul 1;35(4):452-8 PMID: 8103116
  44. Inhibition of the cellular actions of nerve growth factor by staurosporine and K252A results from the attenuation of the activity of the trk tyrosine kinase.
    Biochemistry. 1992 Apr 28;31(16):4034-9 PMID: 1314657
  45. A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer disease.
    Ann Neurol. 1981 Dec;10(6):499-505 PMID: 6173010
  46. Nerve growth factor receptor and choline acetyltransferase remain colocalized in the nucleus basalis (Ch4) of Alzheimer's patients.
    Neurobiol Aging. 1989 Jan-Feb;10(1):67-74 PMID: 2547171
  47. K-252 compounds: modulators of neurotrophin signal transduction.
    J Neurochem. 1992 Dec;59(6):1987-96 PMID: 1431889
  48. Choline acetyltransferase activity in striatum of neonatal rats increased by nerve growth factor.
    Science. 1985 Jul 19;229(4710):284-7 PMID: 2861660
  49. Intracerebral implantation of nerve growth factor-producing fibroblasts protects striatum against neurotoxic levels of excitatory amino acids.
    Neuroscience. 1991;45(3):561-70 PMID: 1837849
  50. Nerve growth factor mRNA in peripheral and central rat tissues and in the human central nervous system: lesion effects in the rat brain and levels in Alzheimer's disease.
    Brain Res. 1986 Jul;387(1):85-92 PMID: 3742235
  51. Distribution of nerve growth factor-like immunoreactive neurons in the adult rat brain following colchicine treatment.
    J Comp Neurol. 1992 Dec 15;326(3):347-62 PMID: 1469118
  52. Nerve growth factor treatment after brain injury prevents neuronal death.
    Science. 1987 Jan 9;235(4785):214-6 PMID: 3798108
  53. Nerve growth factor receptor and choline acetyltransferase colocalization in neurons within the rat forebrain: response to fimbria-fornix transection.
    J Comp Neurol. 1989 Jun 8;284(2):187-204 PMID: 2546981
  54. Axotomy induces nerve growth factor receptor immunoreactivity in spinal motor neurons.
    Brain Res. 1991 May 24;549(2):297-304 PMID: 1653083
  55. The aged monkey basal forebrain: rescue and sprouting of axotomized basal forebrain neurons after grafts of encapsulated cells secreting human nerve growth factor.
    Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10898-902 PMID: 7971980
  56. p75 nerve growth factor receptor immunoreactivity in the human brainstem and spinal cord.
    Brain Res. 1992 Aug 28;589(1):115-23 PMID: 1422811
  57. Expression of choline acetyltransferase and nerve growth factor receptor within hypoglossal motoneurons following nerve injury.
    J Comp Neurol. 1991 Feb 22;304(4):596-607 PMID: 1849521
  58. Distribution of trkB tyrosine kinase immunoreactivity in the rat central nervous system.
    Brain Res. 1993 Sep 17;622(1-2):63-70 PMID: 8242385
  59. Nerve growth factor receptor immunoreactivity in neurons of the normal adult rat spinal cord and its modulation after peripheral nerve lesions.
    J Comp Neurol. 1992 May 8;319(2):285-98 PMID: 1326006
  60. K-252a and staurosporine selectively block autophosphorylation of neurotrophin receptors and neurotrophin-mediated responses.
    Mol Biol Cell. 1992 Jun;3(6):677-86 PMID: 1323351
  61. Nerve growth factor-like immunoreactive profiles in the primate basal forebrain and hippocampal formation.
    J Comp Neurol. 1994 Mar 22;341(4):507-19 PMID: 8201026
  62. The Trk family of tyrosine kinases: receptors for NGF-related neurotrophins.
    Cold Spring Harb Symp Quant Biol. 1992;57:43-51 PMID: 1339678
  63. p140trk mRNA marks NGF-responsive forebrain neurons: evidence that trk gene expression is induced by NGF.
    Neuron. 1992 Sep;9(3):465-78 PMID: 1524827
  64. Induction of nerve growth factor receptor (p75NGFr) mRNA within hypoglossal motoneurons following axonal injury.
    Brain Res Mol Brain Res. 1992 Oct;15(3-4):291-7 PMID: 1331683
  65. NGF and Alzheimer's disease: unfulfilled promise and untapped potential.
    Neurobiol Aging. 1989 Sep-Oct;10(5):543-4; discussion 552-3 PMID: 2812223
  66. Nerve growth factor receptor immunoreactive profiles in the normal, aged human basal forebrain: colocalization with cholinergic neurons.
    J Comp Neurol. 1989 Jul 8;285(2):196-217 PMID: 2547849
  67. TrkA cross-linking mimics neuronal responses to nerve growth factor.
    Mol Biol Cell. 1994 May;5(5):549-63 PMID: 7919537
  68. In situ hybridization of trkB and trkC receptor mRNA in rat forebrain and association with high-affinity binding of [125I]BDNF, [125I]NT-4/5 and [125I]NT-3.
    Eur J Neurosci. 1994 Sep 1;6(9):1389-405 PMID: 8000564
  69. Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections.
    J Neurosci. 1986 Aug;6(8):2155-62 PMID: 3746405
  70. Somatic gene transfer of nerve growth factor promotes the survival of axotomized septal neurons and the regeneration of their axons in adult rats.
    J Neurosci. 1992 Jul;12(7):2849-64 PMID: 1319481
  71. Expression of functional nerve growth factor receptors after gene transfer.
    Science. 1989 Jan 20;243(4889):373-5 PMID: 2536190
  72. Localization of nerve growth factor receptors in cholinergic neurons of the human basal forebrain.
    Neurosci Lett. 1986 Aug 15;69(1):37-41 PMID: 3018635
  73. Dopaminergic neurons in rat ventral midbrain express brain-derived neurotrophic factor and neurotrophin-3 mRNAs.
    J Comp Neurol. 1994 Apr 15;342(3):321-34 PMID: 7912699
  74. Coexpression of neurotrophins and their receptors in neurons of the central nervous system.
    Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6711-5 PMID: 8341689
  75. In situ hybridization detection of trkA mRNA in brain: distribution, colocalization with p75NGFR and up-regulation by nerve growth factor.
    J Comp Neurol. 1994 Mar 15;341(3):324-39 PMID: 8195465
  76. Nerve growth factor receptor immunoreactivity in the nonhuman primate (Cebus apella): distribution, morphology, and colocalization with cholinergic enzymes.
    J Comp Neurol. 1988 Nov 22;277(4):465-86 PMID: 2850304
  77. Nerve growth factor selectively prevents excitotoxin induced degeneration of striatal cholinergic neurones.
    Neurosci Lett. 1992 Jun 22;140(2):161-4 PMID: 1386916
  78. Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor.
    Nature. 1987 Sep 3-9;329(6134):65-8 PMID: 3627243
  79. Nerve growth factor gene expression in the developing rat brain.
    Science. 1986 Oct 17;234(4774):352-5 PMID: 3764415
  80. Distribution of nerve growth factor receptor-like immunoreactivity in the adult rat central nervous system. Effect of colchicine and correlation with the cholinergic system--II. Brainstem, cerebellum and spinal cord.
    Neuroscience. 1990;34(1):89-110 PMID: 2158008
  81. The trk proto-oncogene encodes a receptor for nerve growth factor.
    Cell. 1991 Apr 5;65(1):189-97 PMID: 1849459
  82. Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors: interactions with amphetamine.
    J Neurosci. 1994 Mar;14(3 Pt 1):1262-70 PMID: 8074747
  83. Function of neurotrophic factors in the adult and aging brain and their possible use in the treatment of neurodegenerative diseases.
    Neurobiol Aging. 1989 Sep-Oct;10(5):515-33 PMID: 2682327
  84. Expression of neurotrophins by midbrain dopaminergic neurons.
    Exp Neurol. 1993 Nov;124(1):119-28 PMID: 8282069
  85. Intrastriatal infusions of brain-derived neurotrophic factor: retrograde transport and colocalization with dopamine containing substantia nigra neurons in rat.
    Exp Neurol. 1994 Sep;129(1):15-26 PMID: 7523178
  86. A light and electron microscopic procedure for sequential double antigen localization using diaminobenzidine and benzidine dihydrochloride.
    J Histochem Cytochem. 1986 Nov;34(11):1449-57 PMID: 2430010
  87. NGF receptor (p75)-immunoreactivity within hypoglossal motor neurons following axotomy in monkeys.
    Restor Neurol Neurosci. 1992 Jan 1;4(6):411-7 PMID: 21551675
  88. Function and evolution in the NGF family and its receptors.
    J Neurosci Res. 1992 Aug;32(4):461-70 PMID: 1326636
  89. Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF.
    Nature. 1991 Mar 14;350(6314):158-60 PMID: 1706478
  90. Detection of NGF-like activity in human brain tissue: increased levels in Alzheimer's disease.
    J Neurosci. 1993 Jun;13(6):2540-50 PMID: 8501520
  91. Nerve growth factor.
    Physiol Rev. 1968 Jul;48(3):534-69 PMID: 4875350
  92. Localization of nerve growth factor receptors in the normal human brain and in Alzheimer's disease.
    Neurobiol Aging. 1989 Jan-Feb;10(1):75-87 PMID: 2547172
Article Info
Journal
The Journal of comparative neurology
Abbr.
J Comp Neurol
ISSN
0021-9967
Published
1994-12-22
Pages
587-611
Language
English
Region
United States
NLM ID
0406041
PMCID
PMC2710128
Subset
IM
Grants
NIA NIH HHS · R01 AG010668 · United States
NIA NIH HHS · AG10668 · United States
NIA NIH HHS · P01 AG009466 · United States
NIA NIH HHS · P30 AG010161 · United States
NINDS NIH HHS · P01 NS016033-17A10014 · United States
NIA NIH HHS · AG10161 · United States
NINDS NIH HHS · P01 NS016033 · United States
NIA NIH HHS · AG11482 · United States
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