A single dose of clothianidin exposure induces varying sex-specific behavioral changes in adulthood depending on the developmental stage of its administration.

Clothianidin (CLO), a neonicotinoid that is widely used in forests and agricultural areas, was recently reported to cause toxicity in mammals. Although sensitivity to chemicals varies between sexes and developmental stages, studies that comprehensively evaluate both males and females are limited. Therefore, in this study we utilized murine models to compare the sex-specific differences in behavioral effects following CLO exposure at different developmental stages. We orally administered CLO to male and female mice as a single high-dose solution (80 mg/kg) during the postnatal period (2-week-old), adolescence (6-week-old), or maturity (10-week-old), and subsequently evaluated higher brain function. The behavioral battery test consisted of open field, light/dark transition, and contextual/cued fear conditioning tests conducted at three and seven months of age. After the behavioral test, the brains were dissected and prepared for immunohistochemical staining. We observed behavioral abnormalities in anxiety, spatial memory, and cued memory only in female mice. Moreover, the immunohistochemical analysis showed a reduction in astrocytes within the hippocampus of female mice with behavioral abnormalities. The behavioral abnormalities observed in female CLO-treated mice were consistent with the typical behavioral abnormalities associated with hippocampal astrocyte dysfunction. It is therefore possible that the CLO-induced behavioral abnormalities are at least in part related to a reduction in astrocyte numbers. The results of this study highlight the differences in behavioral effects following CLO exposure between sexes and developmental stages.

A potential mechanism clue to the periodic storm from microglia activation and progressive neuron damage induced by paraquat exposure.

Paraquat (PQ), is characterized by neurotoxicity, which increases the potential risk of Parkinson's disease (PD) exposure in the long-term and low doses. Triggering microglia activation and neuroinflammation is deemed an early event resulting in PD. However, the underlying pathogenesis of PD by PQ is not clear yet. In this article, C57BL/6J mice treated with PQ could successfully act out Parkinson-like. In addition, we observed the fluorescence intensity enhancement of Iba-1 activated microglia with released pro-inflammatory, all ahead of both the damage of dopaminergic neurons in the substantia nigra and corpus striatum of the brain. Surprisingly, the injection of minocycline before PQ for many hours not only can effectively improve the neurobehavioral symptoms of mice but inhibit the activation of microglia and the release of pro-inflammatory substances, even controlling the gradual damage and loss of neurons. A further mechanism of minocycline hampered the expression levels of key signaling proteins PI3K, PDK1, p-AKT, and CD11b (the receptor of microglia membrane recognition), while a large number of inflammatory factors. Our results suggested that the CD11b/PI3K/NOX2 pathway may be a clue that microglia-mediated inflammatory responses and neuronal damage in a PQ-induced abnormal behavior Parkinson-like mouse.

Chronic oral administration of Passiflora incarnata extract has no abnormal effects on metabolic and behavioral parameters in mice, except to induce sleep / 한국실험동물학회지

Although the number of prescriptions and dependence on sleeping pills are increasing, the associations with unexpected abnormal behaviors and metabolic diseases caused by the overuse of sleeping pills are not well understood. In particular, such as abnormal eating-behavior and the occurrence of metabolic disorders caused by psychological unstable states are reported. For this reason, herbal medicine, which has not had such side effects in recent years, is attracting attention as an alternative medicine/food for sleeping inducer. We have used ethanol extracts from Passiflora incarnata (PI) to steadily obtain positive effects on sleep and brain microenvironment. However, as mentioned earlier, sleep-inducing efficacy can only be used safely if the behavioral and metabolic abnormalities do not appear.Thus, in this study, we used Phenomaster equipment to continuously monitor the movement, feeding, water consumption, gas changes, etc. in C57BL/6 mice at a dose of 500 mg/kg/day for 5 consecutive days with PI extract group compared with the control group. Before sacrifice, differences in body composition of mice were also compared. Monitoring of 24 h/5 days through the equipment showed no change in PI-treated group in anything except for significant decrease in blood melatonin levels and activity after PI administration. Taken together, the statistically insignificance of any behavioral and metabolic phenomenon produced by repeated treatment of PI are not only expected to have an accurate sleep effect, but are also free of side effects of the prescribed sleeping pills. This study has given us greater confidence in the safety of the PI extracts we use for sleep-inducer.