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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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Changes in MOR density in different brain structures of neonatally THIM-treated rats. Images are representative photographs of MOR reaction, visualized as brown/dark rings around cells (pointed with arrows). THIM administration led to increase of MOR density in the PAG (a–d) and the CPU (g–h) (increase pointed with black arrows), but to decrease of MOR density in the DG (e–f) (decrease pointed with white arrows). a DMPAG, control, 8-week, ×400; b DMPAG, 240 μg Hg/kg, 8-week, ×400; c DMPAG, control, 20-week, ×400; d DMPAG, 3,000 μg Hg/kg, 20-week, ×400; e DG, control, 20-week, ×100; f DG, 3,000 μg Hg/kg, 20-week, ×100; g CPU, Control, 20-week, ×400; h CPU, 3,000 μg Hg/kg, 20-week, ×400. For interpretation of the references to color in this figure legend, the reader is referred to the online version of this article
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Fig1: Changes in MOR density in different brain structures of neonatally THIM-treated rats. Images are representative photographs of MOR reaction, visualized as brown/dark rings around cells (pointed with arrows). THIM administration led to increase of MOR density in the PAG (a–d) and the CPU (g–h) (increase pointed with black arrows), but to decrease of MOR density in the DG (e–f) (decrease pointed with white arrows). a DMPAG, control, 8-week, ×400; b DMPAG, 240 μg Hg/kg, 8-week, ×400; c DMPAG, control, 20-week, ×400; d DMPAG, 3,000 μg Hg/kg, 20-week, ×400; e DG, control, 20-week, ×100; f DG, 3,000 μg Hg/kg, 20-week, ×100; g CPU, Control, 20-week, ×400; h CPU, 3,000 μg Hg/kg, 20-week, ×400. For interpretation of the references to color in this figure legend, the reader is referred to the online version of this article

Mentions: Results presented in Fig. 1 and Tables 1, 2 and 3 show that early postnatal THIM administration changes MOR density in several brain regions of adult rats (N = 5 per experimental group). Figure 1 illustrates examples of photographs of the analyzed brain regions. The brains of control animals and those that received four injections of lower doses of THIM (12 and 240 μg Hg/kg), were examined on the 8th postnatal week for MOR density in the PAG region. The THIM administration increased MOR density in the PAG in a dose-dependent manner (Table 1). One way ANOVA (Hg dose) revealed statistically significant effect of dose [F(2,6) = 8.087; P = 0.019] in the dorsomedial periaqueductal gray (DMPAG). The post-hoc analysis confirmed a significant effect at dose 240 μg Hg/kg (P = 0.007). In the lateral periaqueductal gray (LPAG) a similar trend was observed, even though one way ANOVA revealed a non-significant effect of Hg dose [F(2,8) = 3.514; P = 0.08].Fig. 1


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)

Changes in MOR density in different brain structures of neonatally THIM-treated rats. Images are representative photographs of MOR reaction, visualized as brown/dark rings around cells (pointed with arrows). THIM administration led to increase of MOR density in the PAG (a–d) and the CPU (g–h) (increase pointed with black arrows), but to decrease of MOR density in the DG (e–f) (decrease pointed with white arrows). a DMPAG, control, 8-week, ×400; b DMPAG, 240 μg Hg/kg, 8-week, ×400; c DMPAG, control, 20-week, ×400; d DMPAG, 3,000 μg Hg/kg, 20-week, ×400; e DG, control, 20-week, ×100; f DG, 3,000 μg Hg/kg, 20-week, ×100; g CPU, Control, 20-week, ×400; h CPU, 3,000 μg Hg/kg, 20-week, ×400. For interpretation of the references to color in this figure legend, the reader is referred to the online version of this article
© Copyright Policy
Related In: Results  -  Collection

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

Fig1: Changes in MOR density in different brain structures of neonatally THIM-treated rats. Images are representative photographs of MOR reaction, visualized as brown/dark rings around cells (pointed with arrows). THIM administration led to increase of MOR density in the PAG (a–d) and the CPU (g–h) (increase pointed with black arrows), but to decrease of MOR density in the DG (e–f) (decrease pointed with white arrows). a DMPAG, control, 8-week, ×400; b DMPAG, 240 μg Hg/kg, 8-week, ×400; c DMPAG, control, 20-week, ×400; d DMPAG, 3,000 μg Hg/kg, 20-week, ×400; e DG, control, 20-week, ×100; f DG, 3,000 μg Hg/kg, 20-week, ×100; g CPU, Control, 20-week, ×400; h CPU, 3,000 μg Hg/kg, 20-week, ×400. For interpretation of the references to color in this figure legend, the reader is referred to the online version of this article
Mentions: Results presented in Fig. 1 and Tables 1, 2 and 3 show that early postnatal THIM administration changes MOR density in several brain regions of adult rats (N = 5 per experimental group). Figure 1 illustrates examples of photographs of the analyzed brain regions. The brains of control animals and those that received four injections of lower doses of THIM (12 and 240 μg Hg/kg), were examined on the 8th postnatal week for MOR density in the PAG region. The THIM administration increased MOR density in the PAG in a dose-dependent manner (Table 1). One way ANOVA (Hg dose) revealed statistically significant effect of dose [F(2,6) = 8.087; P = 0.019] in the dorsomedial periaqueductal gray (DMPAG). The post-hoc analysis confirmed a significant effect at dose 240 μg Hg/kg (P = 0.007). In the lateral periaqueductal gray (LPAG) a similar trend was observed, even though one way ANOVA revealed a non-significant effect of Hg dose [F(2,8) = 3.514; P = 0.08].Fig. 1

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