Acupuncture Can Play an Antidepressant Role by Regulating the Intestinal Microbes and Neurotransmitters in a Rat Model of Depression.

BACKGROUND Acupuncture, which has many good effects and few adverse effects, is widely recognized as an alternative therapy for depression in clinical practice. This study aimed to explore the mechanism of acupuncture in antidepressant treatment. MATERIAL AND METHODS In this experiment, Sprague-Dawley rats were randomly divided into 4 groups: control, chronic unpredictable mild stress (CUMS), acupuncture, and fluoxetine groups. The CUMS, acupuncture, and fluoxetine groups were orphaned and subjected to chronic unpredictable stress for 6 weeks, and the acupuncture and fluoxetine groups were treated with their respective intervention in weeks 4-6. The body weight of rats was monitored weekly. After behavioral tests were completed, serum, feces, and hippocampal tissue of rats were collected. RESULTS The results showed that the acupuncture and fluoxetine treatments could alleviate the behavioral changes caused by CUMS. The treatments increased the total distance of rat crossing in the open-field test, prolonged the activity time of the open cross maze in the open arm, and improved the rate of sucrose consumption in the sucrose preference test. In addition, both the decreased level of dopamine (DA) and 5-hydroxytryptamine (5-HT) in serum and hippocampus caused by CUMS were improved after the treatments with acupuncture and fluoxetine, and the decreased expression of brain-derived neurotrophic factor signaling and the astrocytes in the hippocampus caused by CUMS were increased after the treatments with acupuncture and fluoxetine. Acupuncture and fluoxetine also decreased the ß isoform of calmodulin-dependent protein kinase II in the hippocampus, which was increased by CUMS. Furthermore, acupuncture regulated intestinal microbial disorders caused by CUMS, which reduced the relative abundance ratio of Bacteroidetes/Firmicutes in rats. CONCLUSIONS Our experimental results indicate that acupuncture can alleviate depression-like performance in CUMS rats by regulating intestinal microbes and neurotransmitters.

Altered gray matter structural covariance networks in drug-naïve and treated early HIV-infected individuals.

Background: While regional brain structure and function alterations in HIV-infected individuals have been reported, knowledge about the topological organization in gray matter networks is limited. This research aims to investigate the effects of early HIV infection and combination antiretroviral therapy (cART) on gray matter structural covariance networks (SCNs) by employing graph theoretical analysis. Methods: Sixty-five adult HIV+ individuals (25-50 years old), including 34 with cART (HIV+/cART+) and 31 medication-naïve (HIV+/cART-), and 35 demographically matched healthy controls (HCs) underwent high-resolution T1-weighted images. A sliding-window method was employed to create "age bins," and SCNs (based on cortical thickness) were constructed for each bin by calculating Pearson's correlation coefficients. The group differences of network indices, including the mean nodal path length (Nlp), betweenness centrality (Bc), number of modules, modularity, global efficiency, local efficiency, and small-worldness, were evaluated by ANOVA and post-hoc tests employing the network-based statistics method. Results: Relative to HCs, less efficiency in terms of information transfer in the parietal and occipital lobe (decreased Bc) and a compensated increase in the frontal lobe (decreased Nlp) were exhibited in both HIV+/cART+ and HIV+/cART- individuals (P < 0.05, FDR-corrected). Compared with HIV+/cART- and HCs, less specialized function segregation (decreased modularity and small-worldness property) and stronger integration in the network (increased Eglob and little changed path length) were found in HIV+/cART+ group (P < 0.05, FDR-corrected). Conclusion: Early HIV+ individuals exhibited a decrease in the efficiency of information transmission in sensory regions and a compensatory increase in the frontal lobe. HIV+/cART+ showed a less specialized regional segregation function, but a stronger global integration function in the network.

Longitudinal white matter alterations in SIVmac239-infected rhesus monkeys with and without regular cART treatment.

Objective: To use SIV-mac239-infected Chinese rhesus monkeys to study white matter changes with and without regular combined antiretroviral therapy (cART) and the relationships between the changes and clinical results. Methods: Diffusion tensor imaging (DTI) data were collected at baseline and 10 days, 4 weeks, 12 weeks, 24 weeks, and 36 weeks after viral inoculation. Plasma CD4 T cell counts, CD4/CD8 ratio, plasma viral load, and cerebrospinal fluid (CSF) viral load were collected at baseline and 1 week, 5 weeks, 12 weeks, 24 weeks, and 36 weeks after viral inoculation. Microstructural characteristics were examined within 76 white matter areas defined by the DTI-white matter (WM) atlas for rhesus macaques. Corrections for multiple comparisons were performed using a false discovery rate (p < 0.05, FDR). Correlation analyzes between imaging markers and clinical markers (plasma CD4 T cell counts, CD4/CD8 ratio, plasma viral load, and cerebral spinal fluid viral load) were performed using Pearson correlations. Results: White matter changes in SIV-infected macaques were detected in different brain regions as early as 4 weeks after inoculation. As time progressed, cART reversed, ameliorated, or even enhanced the effects. The CD4 T cell count was mainly associated with DTI metrics before cART, while the CD4/CD8 ratio was associated with white matter changes with and without cART. Viral load was positively associated with mean diffusivity in HIV patients without cART, and the opposite results were seen in HIV patients with cART. Conclusion: SIV-mac239 infection may be an ideal tool for studying HIV-induced changes in the brain. The first white matter changes appeared in a structure adjacent to the periventricular area as early as 4 weeks after inoculation. As time progressed, cART had different effects on different regions, reversing, attenuating, or even progressing the pathology. Moreover, these changes were closely related to the CD4/CD8 ratio and viral load, even after cART.

Current situation and prospect of HIV-associated neurocognitive disorder research in China: Epidemiology, research, diagnosis, and treatment status.

Standards of HIV/AIDS prevention and control in some areas of China are still poor. People live longer with the use of therapeutic drugs, which may lead to an increase in the number of HIV-associated neurocognitive disorders (HAND). However, only a few multicenter and large-scale studies investigating the prevalence and incidence of HAND have been undertaken in China. While the number of HIV/AIDS cases in China is still large, the prevalence of HAND is remains unclear. The diagnosis of HAND in China is mainly based on the international diagnostic scale, to which Chinese features are added. At present, five classes of antiretroviral therapy drugs widely used in China: nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), protease inhibitors, integrase inhibitors, and membrane fusion inhibitors (FIs). There is no specific treatment or drug for HAND in China. Efforts are needed in the following aspects: trying to understand more epidemic features of HAND in China; formulating a unified neuropsychological scale with Chinese characteristics to diagnose HAND and adopt new approaches to identify different stages of HAND; early stage (reversible) accurate hierarchical prediction and diagnosis, combined with artificial intelligence to improve the work efficiency of doctors, and to solve the failure of outpatient diagnosis cases (asymptomatic patients); and exploring and establishing a perfect system for target treatment with HAND.

Longitudinal trajectories of brain volume in combined antiretroviral therapy treated and untreated simian immunodeficiency virus-infected rhesus macaques.

OBJECTIVES: We used simian immunodeficiency virus (SIV)-infected nonhuman primates to investigate longitudinal changes of brain volume caused by SIV and the effect of combined antiretroviral therapy (cART). In addition, the relation between viral load, immune status, and brain volume were explored. DESIGN: A longitudinal study of two healthy controls, five SIVmac239-infected macaques received cART (SIV+cART+) at 40 days postinnoculation, and five SIVmac239-infected macaques received no therapy (SIV+cART-). METHODS: Structural T1-weighted MRI, blood and cerebrospinal fluid testing were acquired at multiple time points for 48 weeks postinfection (wpi). Brain volume was estimated using region of interest (ROI)-based analysis. Volume differences were compared among three groups. Linear regression models tested the associations between brain volumes and biomarkers (viral load, CD4+ T-cell count, CD4+/CD8+ ratio). RESULTS: In our model, brain volume alteration in SIV-infected macaques can be detected at 12 wpi in several brain regions. As the infection progresses, the SIV+cART- macaques displayed generalized gray matter atrophy at the endpoint. Though initiate cART right after acute infection, SIV+cART+ macaques still displayed brain atrophy but showed signs of reversibility. Plasma viral load is mainly associated with subcortical nucleus volume whereas CD4+ T-cell count and CD4+/CD8+ ratio in plasma were associated with widespread cortical volume. CONCLUSION: The SIVmac239-infected Chinese origin macaque is a valid model for neuroHIV. Brain atrophy caused by SIV infection can be relieved, even reversed, by cART. Our model also provides new insights into understanding the pathogenesis of brain injury in people with HIV (PWH).