title: Neonatal administration of thimerosal causes persistent changes in mu opioid receptors in the rat brain.
abstract: Thimerosal added to some pediatric vaccines is suspected in pathogenesis of several neurodevelopmental disorders. Our previous study showed that thimerosal administered to suckling rats causes persistent, endogenous opioid-mediated hypoalgesia. Here we examined, using immunohistochemical staining technique, the density of μ-opioid receptors (MORs) in the brains of rats, which in the second postnatal week received four i.m. injections of thimerosal at doses 12, 240, 1,440 or 3,000 μg Hg/kg. The periaqueductal gray, caudate putamen and hippocampus were examined. Thimerosal administration caused dose-dependent statistically significant increase in MOR densities in the periaqueductal gray and caudate putamen, but decrease in the dentate gyrus, where it was accompanied by the presence of degenerating neurons and loss of synaptic vesicle marker (synaptophysin). These data document that exposure to thimerosal during early postnatal life produces lasting alterations in the densities of brain opioid receptors along with other neuropathological changes, which may disturb brain development.
authors.affiliation: Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Mieszko
authors.initials: M
authors.lastname: Olczak
authors.forename: Michalina
authors.initials: M
authors.lastname: Duszczyk
authors.forename: Pawel
authors.initials: P
authors.lastname: Mierzejewski
authors.forename: Teresa
authors.initials: T
authors.lastname: Bobrowicz
authors.forename: Maria Dorota
authors.initials: MD
authors.lastname: Majewska
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism; D013849:Thimerosal / Q000494:pharmacology*
chemical_list: D017450:Receptors, Opioid, mu; D016708:Synaptophysin; D013849:Thimerosal
references.citation: J Comp Neurol. 2005 Dec 5;493(1):2-8
references.pmid: 16255004
references.citation: Mol Pharmacol. 2004 Dec;66(6):1719-26
references.pmid: 15448191
references.citation: J Neurosci Methods. 1980 Dec;3(2):129-49
references.pmid: 6110810
references.citation: Toxicol Sci. 2009 Aug;110(2):389-400
references.pmid: 19465457
references.citation: Environ Res. 1997;74(1):48-53
references.pmid: 9339214
references.citation: Int J Mol Med. 2005 Dec;16(6):971-7
references.pmid: 16273274
references.citation: J Pharmacol Exp Ther. 2000 Apr;293(1):113-20
references.pmid: 10734160
references.citation: Folia Neuropathol. 1998;36(1):15-23
references.pmid: 9595859
references.citation: Altern Ther Health Med. 2009 Mar-Apr;15(2):56-60
references.pmid: 19284184
references.citation: Proc Natl Acad Sci U S A. 1984 Jun;81(12):3893-7
references.pmid: 6328530
references.citation: Mol Psychiatry. 2004 Sep;9(9):833-45
references.pmid: 15184908
references.citation: Ann Neurol. 1978 Nov;4(5):451-62
references.pmid: 216303
references.citation: Brain Res. 1983 Apr;283(2-3):157-69
references.pmid: 6303517
references.citation: Toxicol Sci. 2007 Jan;95(1):156-62
references.pmid: 17047031
references.citation: Anal Chem. 2003 Aug 15;75(16):4120-4
references.pmid: 14632125
references.citation: Neuro Endocrinol Lett. 2005 Oct;26(5):439-46
references.pmid: 16264412
references.citation: Cancer Res. 2004 Jul 15;64(14):4919-26
references.pmid: 15256464
references.citation: Acta Neurobiol Exp (Wars). 2010;70(2):196-208
references.pmid: 20628443
references.citation: Receptor. 1992 Summer;2(2):109-19
references.pmid: 1335327
references.citation: J Pediatr. 2000 May;136(5):679-81
references.pmid: 10802503
references.citation: Neuropharmacology. 1990 May;29(5):445-52
references.pmid: 2162496
references.citation: Brain Res. 1985 Dec 23;360(1-2):117-29
references.pmid: 3000529
references.citation: Pediatrics. 2008 Feb;121(2):e208-14
references.pmid: 18245396
references.citation: Brain Res. 2009 Dec 8;1301:143-51
references.pmid: 19747466
references.citation: Eur J Pharmacol. 1988 Oct 26;156(1):47-54
references.pmid: 2850210
references.citation: J Neurosci. 1997 Jan 1;17(1):477-92
references.pmid: 8987772
references.citation: Med Hypotheses. 2001 Apr;56(4):462-71
references.pmid: 11339848
references.citation: Toxicol Appl Pharmacol. 2005 Oct 1;208(1):21-8
references.pmid: 16164958
references.citation: Synapse. 1988;2(3):193-9
references.pmid: 2463689
references.citation: Br J Pharmacol. 1978 Jun;63(2):303-8
references.pmid: 208703
references.citation: J Neurol Sci. 2008 Aug 15;271(1-2):110-8
references.pmid: 18482737
references.citation: Prog Brain Res. 2007;163:245-63
references.pmid: 17765723
references.citation: Exp Biol Med (Maywood). 2003 Jun;228(6):660-4
references.pmid: 12773696
references.citation: Proc Natl Acad Sci U S A. 1980 Sep;77(9):5532-6
references.pmid: 6254088
references.citation: Toxicol Appl Pharmacol. 2005 Apr 15;204(2):109-21
references.pmid: 15808517
references.citation: Med Hypotheses. 1986 Jan;19(1):41-5
references.pmid: 3010057
references.citation: Arch Toxicol. 1985 Sep;57(4):260-7
references.pmid: 4091651
references.citation: Int J Toxicol. 2003 Jul-Aug;22(4):277-85
references.pmid: 12933322
references.citation: Pharmacol Rev. 2004 Sep;56(3):351-69
references.pmid: 15317908
references.citation: Mol Psychiatry. 2004 Apr;9(4):358-70
references.pmid: 14745455
references.citation: Brain Dev. 2005 Oct;27(7):509-16
references.pmid: 16198209
references.citation: Mol Pharmacol. 2007 Jan;71(1):123-31
references.pmid: 17005904