Chronic nicotine treatment increases nAChRs and microglial expression in monkey substantia nigra after nigrostriatal damage.
Our previous work had shown that long-term nicotine administration improved dopaminergic markers and nicotinic receptors (nAChRs) in the striatum of monkeys with nigrostriatal damage. The present experiments were done to determine whether nicotine treatment also led to changes in the substantia nigra, the region containing dopaminergic cell bodies. Monkeys were chronically treated with nicotine in the drinking water for 6 months after which they were injected with low dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydrophridine (MPTP) for a further 6-month period. Nicotine was administered until the monkeys were euthanized 2 months after the last MPTP injection. Nicotine treatment did not affect the dopamine transporter or the number of tyrosine hydroxylase positive cells in the substantia nigra of lesioned monkeys. However, nicotine administration did lead to a greater increase in alpha3/alpha6beta2* and alpha4beta2* nAChRs in lesioned monkeys compared to controls. Nicotine also significantly elevated microglia and reduced the number of extracellular neuromelanin deposits in the substantia nigra of MPTP-lesioned monkeys. These findings indicate that long-term nicotine treatment modulates expression of several molecular measures in monkey substantia nigra that may result in an improvement in nigral integrity and/or function. These observations may have therapeutic implications for Parkinson's disease.
Quik
Maryka
M
The Parkinson's Institute, Sunnyvale, CA 94085, USA. mquik@parkinsonsinstitute.org
Campos
Carla
C
Parameswaran
Neeraja
N
Langston
J William
JW
McIntosh
J Michael
JM
Yeluashvili
Michael
M
D000818:Animals; D015415:Biomarkers; D002452:Cell Count; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D008543:Melanins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D018722:Nicotinic Agonists / Q000494:pharmacology / Q000627:therapeutic use; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011978:Receptors, Nicotinic / Q000187:drug effects; D012453:Saimiri; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D015415:Biomarkers; D004298:Dopamine; D008543:Melanins; D018696:Neuroprotective Agents; D009538:Nicotine; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D014446:Tyrosine 3-Monooxygenase; C014121:neuromelanin; C403531:nicotinic receptor alpha4beta2
J Pharmacol Exp Ther. 2006 Oct;319(1):285-92
16837557
Brain Res. 1992 May 29;581(2):283-91
1382801
J Neurochem. 2006 Feb;96(4):1028-41
16412091
J Neurochem. 2006 Feb;96(4):909-16
16417570
J Neurosci. 2002 Oct 15;22(20):8785-9
12388584
Psychopharmacology (Berl). 2007 Feb;190(3):269-319
16896961
J Neurosci. 2007 Aug 1;27(31):8202-18
17670967
J Neurosci. 1992 Jul;12(7):2765-84
1613557
Neuroscience. 2002;112(3):619-30
12074903
Mol Pharmacol. 2002 Jan;61(1):230-8
11752225
J Neural Transm Suppl. 2006;(70):373-81
17017556
J Neurochem. 1992 Sep;59(3):1080-9
1494900
Brain Res. 1988 Jul 12;455(2):332-45
2900058
Prog Neurobiol. 2006 Apr;78(6):364-73
16682109
Mol Pharmacol. 2007 Jul;72(1):52-61
17409284
J Neurosci. 2008 Nov 19;28(47):12318-27
19020025
J Neurochem. 2004 Apr;89(2):337-43
15056277
J Neurochem. 2006 Sep;98(6):1866-75
16882311
Neuroscience. 2006;137(2):565-72
16289885
Neuroscience. 2000;100(1):63-72
10996459
Br J Pharmacol. 2007 Aug;151(7):915-29
17502850
Pharmacol Ther. 2007 Aug;115(2):208-22
17597218
Mol Pharmacol. 2004 Apr;65(4):944-52
15044624
J Neurophysiol. 2007 Dec;98(6):3388-96
17942622
Br J Pharmacol. 2001 Apr;132(8):1650-6
11309235
Mol Pharmacol. 2000 May;57(5):913-25
10779374
J Pharmacol Exp Ther. 2003 Dec;307(3):1090-7
14560040
J Neurosci. 2001 Aug 1;21(15):5494-500
11466420
Neurology. 1988 Aug;38(8):1285-91
3399080
Trends Pharmacol Sci. 2007 May;28(5):229-35
17412429
Mov Disord. 2004 Jun;19(6):614-21
15197698
Arch Neurol. 2007 Jul;64(7):990-7
17620489
Mol Pharmacol. 2005 Jan;67(1):32-41
15470079
J Neurochem. 2007 Jan;100(1):180-90
17227438
Curr Med Chem. 2006;13(5):591-602
16515523
Neuropharmacology. 1990 Mar;29(3):311-4
2325834
Mol Pharmacol. 2005 May;67(5):1639-47
15681595
J Pharmacol Exp Ther. 2007 Jul;322(1):306-15
17446303
J Neurosci. 2006 Apr 26;26(17):4681-9
16641249
Front Biosci. 2008 Jan 01;13:492-504
17981563
Eur J Neurosci. 2007 Jul;26(1):79-89
17581257
FEBS Lett. 2002 Jan 16;510(3):216-20
11801257
Neurology. 1995 Jun;45(6):1041-51
7783862
Brain Res. 2001 Jan 12;888(2):336-342
11150495
Mol Pharmacol. 2005 Jun;67(6):2007-15
15749993
J Pharmacol Exp Ther. 2002 Nov;303(2):633-9
12388645
Neuropharmacology. 2006 Sep;51(3):506-16
16814329
Cell Mol Neurobiol. 2006 Jul-Aug;26(4-6):781-802
16823625