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Neonatal administration of thimerosal causes persistent changes in mu opioid receptors in the rat brain.

Olczak M, Duszczyk M, Mierzejewski P, Bobrowicz T, Majewska MD - Neurochem. Res. (2010)

Bottom Line: Thimerosal added to some pediatric vaccines is suspected in pathogenesis of several neurodevelopmental disorders.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.

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.

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Related in: MedlinePlus

Neuropathological changes in the hippocampi of neonatally THIM-treated rats, 8-week old. Images a–c show dark neurons and ischemic-like degeneration (marked with black arrows) of the hippocampal neurons in the dentate gyrus of THIM-treated rats. a Control group; b THIM dose 12 μg Hg/kg; c THIM dose 240 μg Hg/kg; magnification ×400. Images d–e show diminished synaptophysin reaction (loss of synapses or synaptic marker protein) in the hippocampi of THIM-treated rats (marked with white arrows). d Control group; e THIM dose 240 μg Hg/kg; magnification ×200
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Fig2: Neuropathological changes in the hippocampi of neonatally THIM-treated rats, 8-week old. Images a–c show dark neurons and ischemic-like degeneration (marked with black arrows) of the hippocampal neurons in the dentate gyrus of THIM-treated rats. a Control group; b THIM dose 12 μg Hg/kg; c THIM dose 240 μg Hg/kg; magnification ×400. Images d–e show diminished synaptophysin reaction (loss of synapses or synaptic marker protein) in the hippocampi of THIM-treated rats (marked with white arrows). d Control group; e THIM dose 240 μg Hg/kg; magnification ×200

Mentions: In order to assess if the THIM-induced decline of MOR density in the DG was due to a potential loss of hippocampal neurons or synapses, we conducted a neuropathological examination of this brain region. Figure 2A–C illustrates examples of neuropathological changes in the dorsal hippocampus (Bregma -3.60) of rats, which at neonatal stage received four injections of THIM at doses 12 or 240 μg Hg/kg (N = 5 per group). Characteristic ischemic-like degeneration of neurons and dark neurons were observed in the granular layer of the DG area, CA1 and CA3 fields in THIM-treated rats. These pathological changes were more extensive in animals treated with higher doses of THIM. Neurons in the control group looked normal.Fig. 2


Neonatal administration of thimerosal causes persistent changes in mu opioid receptors in the rat brain.

Olczak M, Duszczyk M, Mierzejewski P, Bobrowicz T, Majewska MD - Neurochem. Res. (2010)

Neuropathological changes in the hippocampi of neonatally THIM-treated rats, 8-week old. Images a–c show dark neurons and ischemic-like degeneration (marked with black arrows) of the hippocampal neurons in the dentate gyrus of THIM-treated rats. a Control group; b THIM dose 12 μg Hg/kg; c THIM dose 240 μg Hg/kg; magnification ×400. Images d–e show diminished synaptophysin reaction (loss of synapses or synaptic marker protein) in the hippocampi of THIM-treated rats (marked with white arrows). d Control group; e THIM dose 240 μg Hg/kg; magnification ×200
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957583&req=5

Fig2: Neuropathological changes in the hippocampi of neonatally THIM-treated rats, 8-week old. Images a–c show dark neurons and ischemic-like degeneration (marked with black arrows) of the hippocampal neurons in the dentate gyrus of THIM-treated rats. a Control group; b THIM dose 12 μg Hg/kg; c THIM dose 240 μg Hg/kg; magnification ×400. Images d–e show diminished synaptophysin reaction (loss of synapses or synaptic marker protein) in the hippocampi of THIM-treated rats (marked with white arrows). d Control group; e THIM dose 240 μg Hg/kg; magnification ×200
Mentions: In order to assess if the THIM-induced decline of MOR density in the DG was due to a potential loss of hippocampal neurons or synapses, we conducted a neuropathological examination of this brain region. Figure 2A–C illustrates examples of neuropathological changes in the dorsal hippocampus (Bregma -3.60) of rats, which at neonatal stage received four injections of THIM at doses 12 or 240 μg Hg/kg (N = 5 per group). Characteristic ischemic-like degeneration of neurons and dark neurons were observed in the granular layer of the DG area, CA1 and CA3 fields in THIM-treated rats. These pathological changes were more extensive in animals treated with higher doses of THIM. Neurons in the control group looked normal.Fig. 2

Bottom Line: Thimerosal added to some pediatric vaccines is suspected in pathogenesis of several neurodevelopmental disorders.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.

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.

Show MeSH
Related in: MedlinePlus