Recent studies have revealed that the gut microbiota participates in the psychiatric behavior changes in disorders associated with alcohol. But it still remains unknown whether alcoholism is involved in changes in gut microbiota and its underlying mechanism is also not clear. Here, we tested the gut microbiota of patients with alcoholism and conducted fecal microbiota transplantation (FMT) from patients with alcoholism to C57BL/6J mice whose gut microbiota had been sharply suppressed with antibiotics (ABX). Then we evaluated their alcohol preference degree, anxiety, and depression-like behaviors and social interaction behaviors, together with molecular changes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Our data indicated that the gut microbiota of patients with alcoholism was drastically different from those of the healthy adults. The abundance of p_Firmicutes was significantly increased whereas p_Bacteroidetes was decreased. Compared to mice transplanted with fecal microbiota from healthy male adults, the mice accepting fecal microbiota from patients with alcoholism showed (a) anxiety-like and depression-like behaviors, (b) decreased social interaction behaviors, (c) spontaneous alcohol preference, and (d) decreased brain-derived neurotrophic factor (BDNF), alpha 1 subunit of GABA type A receptor (α1GABA A R) in mPFC and decreased metabotropic glutamate receptors 1 (mGluR1), protein kinase C (PKC) ε in NAc. Overall, our results suggest that fecal microbiota from patients with

Rotenone is a common pesticide and has been reported as one of the risk factors for Parkinson disease. Rotenone can cause neuronal death or apoptosis through inducing oxidative injury and inhibiting mitochondrial function. As a natural polyphenolic compound, resveratrol possesses the antioxidant capacity and neuroprotective effect. However, the mechanism underlying the neuroprotective effect of resveratrol against rotenone-induced neurotoxicity remains elusive. Here, we treated PC12 cells with rotenone to induce neurotoxicity, and the neurotoxic cells were subjected to resveratrol treatment. The CCK8 and LDH activity assays demonstrated that resveratrol could suppress neurotoxicity induced by rotenone (P < 0.01). The DCFH-DA assay indicated that resveratrol reduced the production of reactive oxygen species (ROS). JC-1 and Hoechst 33342/PI staining revealed that resveratrol attenuated mitochondrial dysfunction and cell apoptosis. Moreover, resveratrol reversed rotenone-induced decrease in SIRT1 expression and Akt1 phosphorylation (P < 0.05). Furthermore, when the SIRT1 and Akt1 activity was inhibited by niacinamide and LY294002, respectively, the neuroprotective effect of resveratrol was remarkably attenuated, which implied that SIRT1 and Akt1 could mediate this process and may be potential molecular targets for intervening rotenone-induced neurotoxicity. In summary, our study demonstrated that resveratrol reduced rotenone-induced oxidative damage, which was partly mediated through activation of the SIRT1/Akt1 signaling pathway. Our study launched a promising avenue for the potential application of resveratrol as a neuroprotective therapeutic agent in Parkinson disease. Anat Rec, 301:1115-1125, 2018. © 2018 Wiley Periodicals, Inc.

Alcohol addiction can cause brain dysfunction and many other diseases. Recently, increasing evidences have suggested that gut microbiota plays a vital role in regulating alcohol addiction. However, the exact mechanism has not yet been elucidated. Here, our study focused on the intestinal bacteria alternations and their correlations with alcohol‐induced neuropsychic behaviors. When consuming alcohol over 3‐week period, animals gradually displayed anxiety/depression‐like behaviors. Moreover, 16S rRNA sequencing showed significant intestinal microflora dysbiosis and distinct community composition. Actinobacteria and Cyanobacteria were both increased at the phylum level. At the genus level, Adlercreutzia spp., Allobaculum spp., and Turicibacter spp. were increased whereas Helicobacter spp. was decreased. We also found that the distances in inner zone measured by open field test and 4% (v/v) alcohol preference percentages were significantly correlated with Adlercreutzia spp. The possible mechanisms were explored and we found the expression of brain‐derived neurotrophic factor (BDNF) and α1 subunit of γ‐aminobutyric acid A receptor (Gabra1) were both decreased in prefrontal cortex (PFC). Especially, further correlation analyses demonstrated that decreased Adlercreutzia spp. was positively correlated with alcohol preference and negatively correlated with anxiety‐like behavior and BDNF/Gabra1 changes in PFC. Similar relationships were observed between Allobaculum spp. and alcohol preference and BDNF changes. Helicobacter spp. and Turicibacter spp. were also correlated with PFC BDNF and hippocampus Gabra1 level. Taken together, our study showed that gut microbiota dysbiosis during chronic alcohol exposure was closely correlated with alcohol‐induced neuropsychic behaviors and BDNF/Gabra1 expression, which provides a new perspective for understanding underlying mechanisms in alcohol addiction. © 2018 BioFactors, 45(2):187–199, 2019

Abuse of methamphetamine (MA) increases the risk of infection of HIV-1, induces considerable neurotoxicity in several brain regions, and impairs the motor and cognitive function in individuals. HIV-1 transactivator of transcription (Tat) has also shown the potent capability to induce neuronal death and impaired brain function. The present study aims to study the synergistic effect of MA and Tat on cytokine synthesis in substantia nigra, striatal dopamine content, and behavioral performance in the rats. Although increased expression of cytokines (interleukin-1β and tumor necrosis factor-α) was observed in the substantia nigra in the rats receiving either MA or Tat alone, a combination of MA and Tat induced a larger and more sustained upregulation of cytokines. In the rats receiving either MA or Tat alone, significant loss in striatal dopamine content was found, which was further exacerbated in the rats receiving both MA and Tat. In the rats receiving either MA or Tat alone, significantly lower performance in the rotarod test and open-field test was observed, whereas the rats receiving both MA and Tat showed more sustained behavioral impairments. These results suggested that Tat protein synergized with MA to induce central neuroinflammation and impair the dopaminergic transmission, thus leading to sustained Parkinson’s-like behavior.

Resveratrol is originally extracted from huzhang, a Chinese herbal medicine. Recently, resveratrol has attracted a great of attention due to its antioxidant and antiapoptotic properties. Although the neuroprotection of resveratrol on neural damages in various models has been well characterized, little is known about the role of resveratrol in methamphetamine (MA) induced neurotoxicity in mesencephalic dopaminergic neurons. Dopaminergic neurons were isolated from midbrain of mouse embryos at embryonic day 15 and cultured in the presence of MA and resveratrol. Cell viability was examined by MTT assay and the apoptosis was assessed using Hoechst33342/PI double staining. To evaluate the Oxidative damage, ROS assay was performed. Moreover, the changes of time course of intracellular free calcium concentration ([Ca(2+) ]i) were analyzed with Fluo-3/AM tracing. The data showed that MA induced the neurotoxicity of cultured cells in a dose-dependent manner. Resveratrol significantly increased cellular viability and retarded cell apoptosis. Furthermore, resveratrol also attenuated MA induced ROS production and intracellular free calcium overload. Our results suggest that resveratrol protects dopaminergic neurons from MA-induced neuronal cytotoxicity, which, at least partly, is mediated by inhibition of [Ca(2+) ]i and oxidative stress. © 2015 BioFactors 41(4):252-260, 2015.

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