Possible mechanisms of bidirectional nuclear transport during neuronal migration

Neuronal migration is a fundamental process of mammalian brain development. In migrating neurons, the nuclear membrane protein Nesprin-2 has been shown to serve as an adaptor to pull the nucleus along microtubule tracks. Current evidence has shown that Nesprin-2 binds to both the minus-end-directed motor dynein as well as the plus-end-directed motor kinesin. However, translocation of neuronal nucleus has long been thought to be primarily driven by dynein motors. Intriguing questions could be raised about the role of kinesin in nuclear transport and how the activities of opposing motors are coordinated through interactions with Nesprin. Combining evidence from recent studies, we propose that Nesprin-2 serves as a switchboard in mediating bidirectional neuronal nuclear movements

Hesperidin Protects against Acute Alcoholic Injury through Improving Lipid Metabolism and Cell Damage in Zebrafish Larvae

Alcoholic liver disease (ALD) is a series of abnormalities of liver function, including alcoholic steatosis, steatohepatitis, and cirrhosis. Hesperidin, the major constituent of flavanone in grapefruit, is proved to play a role in antioxidation, anti-inflammation, and reducing multiple organs damage in various animal experiments. However, the underlying mechanism of resistance to alcoholic liver injury is still unclear. Thus, we aimed to investigate the protective effects of hesperidin against ALD and its molecular mechanism in this study. We established an ALD zebrafish larvae model induced by 350 mM ethanol for 32 hours, using wild-type and transgenic line with liver-specific eGFP expression Tg (lfabp10α:eGFP) zebrafish larvae (4 dpf). The results revealed that hesperidin dramatically reduced the hepatic morphological damage and the expressions of alcohol and lipid metabolism related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, and fads2 compared with ALD model. Moreover, the findings demonstrated that hesperidin alleviated hepatic damage as well, which is reflected by the expressions of endoplasmic reticulum stress and DNA damage related genes (chop, gadd45αa, and edem1). In conclusion, this study revealed that hesperidin can inhibit alcoholic damage to liver of zebrafish larvae by reducing endoplasmic reticulum stress and DNA damage, regulating alcohol and lipid metabolism

Corrigendum: Modified Xiaoyaosan (MXYS) Exerts Anti-depressive Effects by Rectifying the Brain Blood Oxygen Level-Dependent FMRI Signals and Improving Hippocampal Neurogenesis in Mice

As the traditional Chinese herbal formula, Xiaoyaosan and its modified formula have been described in many previous studies with definite anti-depressive effects, but its underlying mechanism remains mystery. Previous work in our lab has demonstrated that depression induced by chronic stress could generate brain blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals disorder, accompanied by the impairment of hippocampal neuronal plasticity, decrease of brain-derived neurotrophic factor, and reduction of the number and complexity of adult neurons in the dentate gyrus. We hypothesized that herbal formula based on Xiaoyaosan could exert anti-depressive effects through restoring these neurobiological dysfunctions and rectifying BOLD-fMRI signals. To test this hypothesis, we examined the effect of modified Xiaoyaosan (MXYS) on depressive-like behaviors, as well as hippocampal neurogenesis and BOLD signals in a mice model of chronic unpredictable mild stress (CUMS)-induced depression. MXYS exerted anti-depressant effects on CUMS-induced depression that were similar to the effects of classical antidepressants drug (fluoxetine hydrochloride), with a significant alleviation of depressive-like behaviors, an improvement of hippocampal neurogenesis, and a reversal of activation of BOLD in the limbic system, particularly in the hippocampus. These results suggested that MXYS attenuated CUMS-induced depressive behaviors by rectifying the BOLD signals in the mice hippocampus. These novel results demonstrated that MXYS had anti-depressive effects accompanied by improving BOLD signals and hippocampal neurogenesis, which suggested that BOLD-fMRI signals in brain regions could be a key component for the evaluation of novel antidepressant drugs

Modified Xiaoyaosan (MXYS) Exerts Anti-depressive Effects by Rectifying the Brain Blood Oxygen Level-Dependent fMRI Signals and Improving Hippocampal Neurogenesis in Mice

As the traditional Chinese herbal formula, Xiaoyaosan and its modified formula have been described in many previous studies with definite anti-depressive effects, but its underlying mechanism remains mystery. Previous work in our lab has demonstrated that depression induced by chronic stress could generate brain blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals disorder, accompanied by the impairment of hippocampal neuronal plasticity, decrease of brain-derived neurotrophic factor, and reduction of the number and complexity of adult neurons in the dentate gyrus. We hypothesized that herbal formula based on Xiaoyaosan could exert anti-depressive effects through restoring these neurobiological dysfunctions and rectifying BOLD-fMRI signals. To test this hypothesis, we examined the effect of modified Xiaoyaosan (MXYS) on depressive-like behaviors, as well as hippocampal neurogenesis and BOLD signals in a mice model of chronic unpredictable mild stress (CUMS)-induced depression. MXYS exerted anti-depressant effects on CUMS-induced depression that were similar to the effects of classical antidepressants drug (fluoxetine hydrochloride), with a significant alleviation of depressive-like behaviors, an improvement of hippocampal neurogenesis, and a reversal of activation of BOLD in the limbic system, particularly in the hippocampus. These results suggested that MXYS attenuated CUMS-induced depressive behaviors by rectifying the BOLD signals in the mice hippocampus. These novel results demonstrated that MXYS had anti-depressive effects accompanied by improving BOLD signals and hippocampal neurogenesis, which suggested that BOLD-fMRI signals in brain regions could be a key component for the evaluation of novel antidepressant drugs

Abnormal voxel-mirrored homotopic connectivity in first-episode major depressive disorder using fMRI: a machine learning approach

ObjectiveTo explore the interhemispheric information synergy ability of the brain in major depressive disorder (MDD) patients by applying the voxel-mirrored homotopic connectivity (VMHC) method and further explore the potential clinical diagnostic value of VMHC metric by a machine learning approach.Methods52 healthy controls and 48 first-episode MDD patients were recruited in the study. We performed neuropsychological tests and resting-state fMRI scanning on all subjects. The VMHC values of the symmetrical interhemispheric voxels in the whole brain were calculated. The VMHC alterations were compared between two groups, and the relationship between VMHC values and clinical variables was analyzed. Then, abnormal brain regions were selected as features to conduct the classification model by using the support vector machine (SVM) approach.ResultsCompared to the healthy controls, MDD patients exhibited decreased VMHC values in the bilateral middle frontal gyrus, fusiform gyrus, medial superior frontal gyrus and precentral gyrus. Furthermore, the VMHC value of the bilateral fusiform gyrus was positively correlated with the total Hamilton Depression Scale (HAMD). Moreover, SVM analysis displayed that a combination of all clusters demonstrated the highest area under the curve (AUC) of 0.87 with accuracy, sensitivity, and specificity values of 86.17%, 76.74%, and 94.12%, respectively.ConclusionMDD patients had reduced functional connectivity in the bilateral middle frontal gyrus, fusiform gyrus, medial superior frontal gyrus and precentral gyrus, which may be related to depressive symptoms. The abnormality in these brain regions could represent potential imaging markers to distinguish MDD patients from healthy controls

Sinomenine Protects Against Morphine Dependence through the NMDAR1/CAMKII/CREB Pathway: A Possible Role of Astrocyte-Derived Exosomes

Sinomenine is a nonaddictive alkaloid used to prevent morphine dependence, even thoughits mechanism isnot fully understood. Astrocytes aggravate the pathological process in their neighboring cellsthrough exosomes in central nervous system diseases. However, the effect of sinomenine on astrocyte-derived exosomes for the amelioration of morphine dependence has not been reported yet. In this study, we found that sinomenine prevented the morphine-induced conditionedplace preference in mice. Sinomenine reduced the levels of cAMP and intracellular Ca2+ in morphine-treated SH-SY5Y cells. Moreover, sinomenine inhibited the expressions of p-NMDAR1/NMDAR1, p-CAMKII/CAMKII, and p-CREB/CREB in the hippocampusof morphine-dependent mice and SH-SY5Y cells. Furthermore, we found that sinomenine inhibitedthe morphine-induced activation of astrocytesin vivo and in vitro. Afterwards, exosomes were isolated from cultured primary astrocytes treated with phosphate buffer saline (PBS, ctl-exo), morphine (mor-exo), or morphine and sinomenine (Sino-exo). Subsequently, morphine-treated SH-SY5Y cells were treated with ctl-exo, mor-exo, and Sino-exo. Results showed that Sino-exo reduced the level of cAMP, intracellular Ca2+, and the expression of p-CAMKII/CAMKII and p-CREB/CREB in morphine-treated SH-SY5Y cells. In conclusion, we demonstrated that sinomenine exhibited protective effects against morphine dependencein vivo and in vitro through theNMDAR1/CAMKII/CREB pathway. Sinomenine-induced alterationof the function of astrocyte-derived exosomes may contribute to the antidependence effects of sinomenine in morphine dependence