• Toxicological Research
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• v.30 no.4
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• pp.267-276
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• 2014

Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity.

• Journal of Oriental Neuropsychiatry
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• v.30 no.4
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• pp.357-369
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• 2019

Objectives: This study was designed to examine the effect of Hominis Placenta Pharmacopuncture on the change in behavior, sleep-related hormones, inflammatory cytokines, anti-oxidants, weight, blood, and serum on rats given chronic physical stress. Methods: Wistar rats older than age 10 weeks were used in this experiment. They were divided into six groups. The normal group was not given stress. The control group was given only chronic physical stress and no treatment. The positive control group was given chronic physical stress and treated with zolpidem. Three Hominis Placenta Pharmacopuncture (HPP) groups were given chronic physical stress, then treated with different concentrations of HPP; HPP-0.5× (0.5 times diluted), HPP-1× (undiluted) and HPP-2× (2 times condensed). The changes of values of Nestlet Shredding results, weight, Melatonin, Gamma-aminobutylic Acid (GABA), Tumor Necrosis Factor Alpha (TNF-α), Interleukin-6 (IL-6), Superoxide dismutase (SOD), glutathione peroxidase (GPx), AST, ALT, BUN, Creatinine, and leukocytes were observed during the experiment. Results: The changes in chronic physical stress of the rat model were as follow. The Nestlet Shredding result increased in the control group compared to the normal group (p<0.05), and decreased in the HPP-1× and HPP-2× compared to the control group (p<0.05). The amount of weight gain showed increasing tendency in the HPP-2× compared to the control group since the second week. The GABA increased (p<0.05) and Melatonin also showed certain increasing tendency in the HPP-1× and HPP-2× compared to the control group. The TNF-α and IL-6 increased in the control group compared to the normal group (p<0.01), and decreased in all the HPPs compared to the control group (p<0.05). The SOD level decreased in the control group compared to the normal group (p<0.01), and increased in all the HPPs compared to the control group (p<0.05). GPx, AST, ALT, Bun, Creatinine and leukocytes showed no noticeable difference among all groups. Conclusions: Hominis Placenta Pharmacopuncture was effective in increasing weight, GABA, Melatonin, SOD, and decreasing Nestlet Shredding and inflammatory cytokines, suggesting that it consequently facilitates in relieving physical stress.