G protein-coupled estrogen receptor 1 deficiency impairs adult hippocampal neurogenesis in mice with schizophrenia.

OBJECTIVE: This study aimed to confirm that G protein-coupled estrogen receptor 1 (GPER1) deficiency affects cognitive function by reducing hippocampal neurogenesis via the PKA/ERK/IGF-I signaling pathway in mice with schizophrenia (SZ). METHODS: Mice were divided into four groups, namely, KO Con, WT Con, KO Con, and WT SZ (n = 12 in each group). All mice were accustomed to the behavioral equipment overnight in the testing service room. The experimental conditions were consistent with those in the animal house. Forced swimming test and Y-maze test were conducted. Neuronal differentiation and maturation were detected using immunofluorescence and confocal imaging. The protein in the PKA/ERK/IGF-I signaling pathway was tested using Western blot analysis. RESULTS: GPER1 KO aggravated depression during forced swimming test and decreased cognitive ability during Y-maze test in the mouse model of dizocilpine maleate (MK-801)-induced SZ. Immunofluorescence and confocal imaging results demonstrated that GPER1 knockout reduced adult hippocampal dentate gyrus neurogenesis. Furthermore, GPER1-KO aggravated the hippocampal damage induced by MK-801 in mice through the PKA/ERK/IGF-I signaling pathway. CONCLUSIONS: GPER1 deficiency reduced adult hippocampal neurogenesis and neuron survival by regulating the PKA/ERK/IGF-I signaling pathway in the MK-801-induced mouse model of SZ.

Immp2l Mutation Induces Mitochondrial Membrane Depolarization and Complex III Activity Suppression after Middle Cerebral Artery Occlusion in Mice.

OBJECTIVE: We previously reported that mutations in inner mitochondrial membrane peptidase 2-like (Immp2l) increase infarct volume, enhance superoxide production, and suppress mitochondrial respiration after transient cerebral focal ischemia and reperfusion injury. The present study investigated the impact of heterozygous Immp2l mutation on mitochondria function after ischemia and reperfusion injury in mice. METHODS: Mice were subjected to middle cerebral artery occlusion for 1 h followed by 0, 1, 5, and 24 h of reperfusion. The effects of Immp2l+/- on mitochondrial membrane potential, mitochondrial respiratory complex III activity, caspase-3, and apoptosis-inducing factor (AIF) translocation were examined. RESULTS: Immp2l+/- increased ischemic brain damage and the number of TUNEL-positive cells compared with wild-type mice. Immp2l+/- led to mitochondrial damage, mitochondrial membrane potential depolarization, mitochondrial respiratory complex III activity suppression, caspase-3 activation, and AIF nuclear translocation. CONCLUSION: The adverse impact of Immp2l+/- on the brain after ischemia and reperfusion might be related to mitochondrial damage that involves depolarization of the mitochondrial membrane potential, inhibition of the mitochondrial respiratory complex III, and activation of mitochondria-mediated cell death pathways. These results suggest that patients with stroke carrying Immp2l+/- might have worse and more severe infarcts, followed by a worse prognosis than those without Immp2l mutations.

A novel method dependent only on the mixture information (MIM) for evaluating the toxicity of mixture.

Compound contamination and toxicity interaction necessitate the development of models that have an insight into the combined toxicity of chemicals. In this paper, a novel and simple model dependent only on the mixture information (MIM), was developed. Firstly, the concentration-response data of seven groups of binary and multi-component (pseudo-binary) mixtures with different mixture ratios to Vibrio qinghaiensis sp.-Q67 were determined using the microplate toxicity analysis. Then, a desirable non-linear function was selected to fit the data. It was found that there are good linear correlations between the location parameter (α) and mixture ratio (p) of a component and between the steepness (ß) and p. Based on the correlations, a mixture toxicity model independent of pure component toxicity profiles was built. The model can be used to accurately estimate the toxicities of the seven groups of mixtures, which greatly simplified the predictive procedure of the combined toxicity.

Behavioral effects of sinomenine in murine models of anxiety.

The present study was designed to investigate the putative anxiolytic-like effect of sinomenine in three experimental models of anxiety in male rats and mice. Use of the elevated plus-maze test revealed that sinomenine (20 and 40 mg/kg, p.o.) increased the percentage of open arm entries and diazepam (2 mg/kg, p.o.) increased the percentage of open arm entries, the percentage of time spent on open arms and total arm entries in mice. In the light/dark transition test, sinomenine (20 and 40 mg/kg, p.o.) increased time spent in the light area and diazepam (2 mg/kg, p.o.) increased time spent in the light area and the overall movements in mice. In the social interaction test, the sinomenine-treated animals significantly increased social interaction time in low light unfamiliar (7 mg/kg, p.o.) and high light unfamiliar conditions (7 and 14 mg/kg, p.o.) as well as diazepam (3 mg/kg, p.o.). Sinomenine (28 mg/kg, p.o.) can also decrease squares entered in rats in social interaction test under low light unfamiliar condition. In the open-field test, sinomenine (160 mg/kg) decreased squares entered in mice. Thus, these findings indicated that sinomenine exhibited anxiolytic-like effect.

The effects of angelica essential oil in social interaction and hole-board tests.

In our previous studies, we have demonstrated the anxiolytic effects of angelica essential oil in three anxiety models using mice. This study aimed to characterize the similar behavior effects of angelica essential oil in the social interaction test of anxiety and the hole-board test of exploration and locomotor activity in rats. These results indicate that angelica essential oil possessed a wide range of anxiolytic properties. In the social interaction test, angelica essential oil decreased aggressive behaviors at the doses of 21 and 42 mg/kg, while the doses of 21 and 42 mg/kg significantly increased social interaction time of the high light, unfamiliar test condition and 21 mg/kg could also prolong social interaction time of the high light, familiar test condition. In the hole-board test, angelica essential oil at 10.5 mg/kg significantly increased head-dipping counts and duration. Thus, our findings suggest the potential usefulness of angelica essential oil against various types of anxiety-related disorders and social failure.

Anxiolytic-like effect of paeonol in mice.

The present study in mice compared the putative anxiolytic-like effect of paeonol, a phenolic component from the root bark of Paeonia moutan, with the benzodiazepine diazepam in the elevated plus maze and the light/dark box-test. The comparison was also with regard to locomotor activity (open-field test) and myorelaxant potential (inclined plane test). As with 2 mg/kg diazepam, paeonol (at 17.5 mg/kg) increased the percentage of time spent on open arms in the elevated plus maze and increased the time spent in the light area of the light/dark box (at 8.75 and 17.5 mg/kg). Since paeonol, in contrast to diazepam, had no effect on either the number of squares entered in the open-field test or in the inclined plane test, its side-effect profile is considered as superior to the benzodiazepine.

Possible anxiolytic effects of taurine in the mouse elevated plus-maze.

The effects of taurine, an inhibitory amino acid, on the behavior of male mice were examined in the elevated plus-maze test of anxiety. Acute taurine treatment (60 mg/kg, PO) significantly increased the percentage of time spent in the open arms. Moreover, when taurine was administered daily for seven days and the plus-maze test was conducted 40 minutes after the last administration, a significant increase of the percentage of time in the open arms was observed even at dose of 2.5 mg/kg, however the open arm entries and the total entries were unaffected at any dose tested. In order to get a comprehensive profile of drug action, detailed behavioral analyses were further exerted. Single administration of 60 mg/kg taurine can significantly reduce the total rears. The results suggest that taurine have some anxiolytic-like properties, although its effects seem more limited and are not consistent with those presented by classic anxiolytics, such as diazepam.