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Szot P, Franklin A, Sikkema C, et al. Sequential Loss of LC Noradrenergic and Dopaminergic Neurons Results in a Correlation of Dopaminergic Neuronal Number to Striatal Dopamine Concentration. Front Pharmacol. 2012;3:184doi: 10.3389/fphar.2012.00184.
Szot, P., Franklin, A., Sikkema, C., Wilkinson, C. W., & Raskind, M. A. (2012). Sequential Loss of LC Noradrenergic and Dopaminergic Neurons Results in a Correlation of Dopaminergic Neuronal Number to Striatal Dopamine Concentration. Frontiers in pharmacology, 3184. https://doi.org/10.3389/fphar.2012.00184
Szot, Patricia, et al. "Sequential Loss of LC Noradrenergic and Dopaminergic Neurons Results in a Correlation of Dopaminergic Neuronal Number to Striatal Dopamine Concentration." Frontiers in pharmacology vol. 3 (2012): 184. doi: https://doi.org/10.3389/fphar.2012.00184
Szot P, Franklin A, Sikkema C, Wilkinson CW, Raskind MA. Sequential Loss of LC Noradrenergic and Dopaminergic Neurons Results in a Correlation of Dopaminergic Neuronal Number to Striatal Dopamine Concentration. Front Pharmacol. 2012 Oct 22;3:184. doi: 10.3389/fphar.2012.00184. eCollection 2012. PMID: 23129999; PMCID: PMC3487487.
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Front Pharmacol. 2012 Oct 22;3:184. doi: 10.3389/fphar.2012.00184. eCollection 2012.

Sequential Loss of LC Noradrenergic and Dopaminergic Neurons Results in a Correlation of Dopaminergic Neuronal Number to Striatal Dopamine Concentration.

Frontiers in pharmacology

Patricia Szot, Allyn Franklin, Carl Sikkema, Charles W Wilkinson, Murray A Raskind

Affiliations

  1. Mental Illness Research, Education and Clinical Center, Veterans Administration Puget Sound Health Care System Seattle, WA, USA ; Department of Psychiatry and Behavioral Sciences, University of Washington Seattle, WA, USA.

PMID: 23129999 PMCID: PMC3487487 DOI: 10.3389/fphar.2012.00184

Abstract

Noradrenergic neurons in the locus coeruleus (LC) are significantly reduced in Parkinson's disease (PD) and the LC exhibits neuropathological changes early in the disease process. It has been suggested that a loss of LC neurons can enhance the susceptibility of dopaminergic neurons to damage. To determine if LC noradrenergic innervation protects dopaminergic neurons from damage, the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was administered to adult male C57Bl/6 mice 3 days after bilateral LC administration of 6-hydroxydopamine (6OHDA), a time when there is a significant reduction in LC neuronal number and innervation to forebrain regions. To assess if LC loss can affect dopaminergic loss four groups of animals were studied: control, 6OHDA, MPTP, and 6OHDA + MPTP; animals sacrificed 3 weeks after MPTP administration. The number of dopaminergic neurons in the substantia nigra (SN) and ventral tegmental area (VTA), and noradrenergic neurons in the LC were determined. Catecholamine levels in striatum were measured by high-pressure liquid chromatography. The loss of LC neurons did not affect the number of dopaminergic neurons in the SN and VTA compared to control; however, LC 6OHDA significantly reduced striatal dopamine (DA; 29% reduced) but not norepinephrine (NE) concentration. MPTP significantly reduced SN and VTA neuronal number and DA concentration in the striatum compared to control; however, there was not a correlation of striatal DA concentration with SN or VTA neuronal number. Administration of 6OHDA prior to MPTP did not enhance MPTP-induced damage despite an effect of LC loss on striatal DA concentration. However, the loss of LC neurons before MPTP resulted now in a correlation between SN and VTA neuronal number to striatal DA concentration. These results demonstrate that the loss of either LC or DA neurons can affect the function of each others systems, indicating the importance of both the noradrenergic and dopaminergic system in PD.

Keywords: 6-hydroxydopamine; MPTP; catecholamines; locus coeruleus; striatum; substantia nigra; ventral tegmentum area

References

  1. Brain Res. 2011 Feb 10;1373:240-52 - PubMed
  2. J Comp Neurol. 1975 Oct 15;163(4):467-505 - PubMed
  3. J Neurochem. 1998 Jun;70(6):2468-76 - PubMed
  4. Int J Neuropsychopharmacol. 2011 Mar;14(2):187-200 - PubMed
  5. Eur J Pharmacol. 1993 Jun 4;236(3):487-9 - PubMed
  6. J Pharmacol Exp Ther. 1999 Feb;288(2):798-804 - PubMed
  7. Psychopharmacology (Berl). 1998 Apr;136(3):299-303 - PubMed
  8. Brain Res. 1986 Jun 18;376(1):117-24 - PubMed
  9. Neuroscience. 2007 Oct 26;149(2):303-14 - PubMed
  10. J Comp Neurol. 1985 Dec 1;242(1):56-92 - PubMed
  11. Biochem Pharmacol. 2007 Jul 15;74(2):177-90 - PubMed
  12. Brain Res. 1994 Dec 30;668(1-2):261-5 - PubMed
  13. J Neural Transm Suppl. 2007;(72):113-20 - PubMed
  14. Neuroscience. 2003;122(3):627-35 - PubMed
  15. J Pharmacol Exp Ther. 1997 Oct;283(1):100-7 - PubMed
  16. J Neurosci. 2009 Jun 24;29(25):8103-13 - PubMed
  17. Eur J Pharmacol. 1993 Mar 16;233(1):79-84 - PubMed
  18. Folia Neuropathol. 1997;35(2):80-6 - PubMed
  19. Science. 1984 Jun 29;224(4656):1451-3 - PubMed
  20. Eur J Pharmacol. 1981 Jun 19;72(2-3):173-88 - PubMed
  21. Neurology. 1987 Jan;37(1):42-6 - PubMed
  22. Int J Neuropsychopharmacol. 2008 Aug;11(5):625-39 - PubMed
  23. Brain Res. 2010 Jan 15;1310:189-99 - PubMed
  24. Brain Res Mol Brain Res. 1997 Feb;44(1):46-54 - PubMed
  25. Prog Neurobiol. 2007 Jan;81(1):29-44 - PubMed
  26. Eur J Pharmacol. 1995 Sep 5;283(1-3):99-102 - PubMed
  27. Brain Res. 1983 Mar 21;263(2):344-7 - PubMed
  28. Brain Res. 1990 Jul 16;523(1):134-8 - PubMed
  29. Neuroscience. 2010 Mar 10;166(1):279-91 - PubMed
  30. J Neurosci Res. 2004 May 15;76(4):539-50 - PubMed
  31. Brain Res. 1992 Aug 21;588(2):261-9 - PubMed
  32. Brain. 1999 Aug;122 ( Pt 8):1437-48 - PubMed
  33. Synapse. 2000 Dec 1;38(3):363-8 - PubMed
  34. J Comp Neurol. 1990 Mar 22;293(4):616-31 - PubMed
  35. Eur J Neurosci. 2003 Jun;17(12):2586-92 - PubMed
  36. Neurobiol Aging. 2003 Mar-Apr;24(2):197-211 - PubMed
  37. J Comp Neurol. 1989 Sep 15;287(3):373-92 - PubMed
  38. Science. 1977 Feb 18;195(4279):646-53 - PubMed
  39. Eur J Neurosci. 1995 Aug 1;7(8):1707-13 - PubMed
  40. J Neural Transm Gen Sect. 1993;93(1):11-25 - PubMed
  41. Eur Neurol. 1991;31 Suppl 1:48-59 - PubMed
  42. Clin Exp Neurol. 1986;22:155-64 - PubMed
  43. J Histochem Cytochem. 1989 Sep;37(9):1435-42 - PubMed
  44. Proc Natl Acad Sci U S A. 1985 Jan;82(2):617-21 - PubMed
  45. J Comp Neurol. 1979 Sep 1;187(1):117-43 - PubMed
  46. Brain Res. 1977 May 20;127(1):25-53 - PubMed
  47. J Neurol Neurosurg Psychiatry. 1991 May;54(5):388-96 - PubMed
  48. J Neurochem. 1993 Sep;61(3):1024-34 - PubMed
  49. Brain Res. 2002 Aug 16;946(2):239-46 - PubMed
  50. Br J Pharmacol. 1976 Dec;58(4):521-7 - PubMed
  51. Neuroscience. 1991;41(2-3):507-23 - PubMed
  52. J Neurosci Res. 1990 Mar;25(3):395-404 - PubMed
  53. Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13804-9 - PubMed
  54. Brain Res. 1996 Oct 7;735(2):349-53 - PubMed
  55. Brain Res. 1993 Jun 18;614(1-2):21-8 - PubMed
  56. Naunyn Schmiedebergs Arch Pharmacol. 1997 Feb;355(2):267-72 - PubMed
  57. Brain Res. 1979 Dec 7;178(1):17-40 - PubMed
  58. Neuroscience. 1990;38(1):245-53 - PubMed
  59. Neurochem Res. 1993 Dec;18(12):1321-7 - PubMed
  60. J Neurosci. 2006 Jan 11;26(2):467-78 - PubMed
  61. Adv Neurol. 1987;45:19-34 - PubMed
  62. Neurochem Int. 1994 Oct;25(4):395-400 - PubMed
  63. Life Sci. 1981 Feb 2;28(5):467-75 - PubMed
  64. J Neural Transm (Vienna). 2006 Sep;113(9):1119-29 - PubMed
  65. Neurodegeneration. 1995 Sep;4(3):257-69 - PubMed
  66. Brain Res. 2006 Sep 13;1109(1):45-53 - PubMed
  67. Life Sci. 1992;50(14):995-9 - PubMed
  68. Neuropathol Appl Neurobiol. 1993 Dec;19(6):519-23 - PubMed
  69. Eur J Pharmacol. 1989 Jun 8;165(1):11-8 - PubMed
  70. Exp Neurol. 1988 Jul;101(1):75-86 - PubMed
  71. Behav Brain Res. 2004 May 5;151(1-2):191-9 - PubMed
  72. Neurosci Lett. 1985 Aug 5;58(3):321-6 - PubMed
  73. Neuroscience. 2012 Aug 2;216:143-57 - PubMed
  74. Expert Rev Neurother. 2009 Feb;9(2):279-90 - PubMed
  75. Pharmacol Biochem Behav. 2012 Jan;100(3):607-15 - PubMed
  76. J Neurosci. 1989 May;9(5):1481-9 - PubMed
  77. J Neurol Sci. 2006 Oct 25;248(1-2):255-8 - PubMed
  78. Arch Neurol. 2003 Mar;60(3):337-41 - PubMed

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