Neuroreport最新文献

Alcohol use disorder (AUD) is a highly prevalent public health problem. The ghrelin system has been identified as a potential target for therapeutic intervention for AUD. Previous work showed that systemic administration of the growth hormone secretagogue receptor (GHSR) antagonist DLys reduced alcohol intake and preference in male mice. Yet, it is unclear whether central or peripheral GHSRs mediated these effects. We hypothesized that alcohol consumption is driven by central GHSRs and addressed this hypothesis by testing the effects of central administration of DLys. Male C57BL/6J mice consumed alcohol in a two-bottle choice procedure (10% ethanol versus water). DLys (2 nmol) was administered intracerebroventricularly for 7 days to examine alcohol intake and preference. DLys decreased alcohol intake and preference but had no effect on food intake. The effects on alcohol intake and preference persisted after several administrations, indicating lack of tolerance to DLys' effects. These results suggest that central administration of DLys is sufficient to reduce alcohol drinking and that DLys remains effective after several administrations when given intracerebroventricularly. Moreover, this work suggests that the effects of intracerebroventricularly administered DLys are specific to alcohol and do not generalize to other calorie-driven behaviors.

In this study, the postoperative cognitive dysfunction (POCD) mouse model was established to observe the changes in inflammation, blood-brain barrier permeability, and myelin sheath, and we explore the effect of ginsenoside Rg1 pretreatment on improving POCD syndrome. The POCD model of 15- to 18-month-old mice was carried out with internal fixation of tibial fractures under isoflurane anesthesia. Pretreatment was performed by continuous intraperitoneal injection of ginsenoside Rg1(40 mg/kg/day) for 14 days before surgery. The cognitive function was detected by the Morris water maze. The contents of interleukin-1β and tumor necrosis factor-α in the hippocampus, cortex, and serum were detected by ELISA. The permeability of blood-brain barrier was observed by Evans blue. The mRNA levels and protein expression levels of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), myelin basic protein (MBP), beta-catenin, and cyclin D1 in the hippocampus were analyzed by quantitative PCR and western blotting. The protein expression levels of ZO-1 and Wnt1 in the hippocampus were analyzed by western blotting. Finally, the localizations of CNPase and MBP in the hippocampus were detected by immunofluorescence. Ginsenoside Rg1 can prevent POCD, peripheral and central inflammation, and blood-brain barrier leakage, and reverse the downregulation of ZO-1, CNPase, MBP, and Wnt pathway-related molecules in aged mice. Preclinical studies suggest that ginsenoside Rg1 improves postoperative cognitive function in aged mice by protecting the blood-brain barrier and myelin sheath, and its specific mechanism may be related to the Wnt/β-catenin pathway.

The objective is to determine the distribution of glutamic acid decarboxylase (GAD) in the olfactory bulb of a crocodilian, Caiman crocodilus . Avidin-biotin immunohistochemical methodology using a polyclonal antibody to GAD raised in sheep was employed. The following controls were used: substitution of the primary antibody with preimmune sheep serum at concentrations equal to that of the primary antibody; omission of the primary antibody; and omission of the primary antibody and biotinylated rabbit antisheep immunoglobulin. No GAD (+) cells were observed in the control sections. Based on cell and fiber staining, the layering and neuronal organization of the olfactory bulb in Caiman were similar to other vertebrates, including other reptiles. The following elements were GAD (+): granule cells, certain neurons in the outer plexiform layer, periglomerular neurons, and the glomeruli themselves. GAD (+) puncta were present throughout the olfactory bulb. In conclusion, these results in Caiman were similar, in part, to comparable studies in mammals and birds. Taken together, these data indicate that crocodiles not only have a similar pattern of layers that other amniotes possess but also that the immunocytochemical signatures of certain elements of the olfactory bulb are likewise shared.

The aim of this study was to investigate the impact and underlying molecular mechanisms of electroacupuncture on mice with poststroke depression (PSD). Mice were randomly allocated into sham, PSD, and electroacupuncture groups. Mice in the PSD and electroacupuncture groups underwent middle cerebral artery occlusion (MCAO) surgery following with sedentary behavior. Electroacupuncture targeting Zusanli (ST36) acupoint was performed 24 h after MCAO for 4 weeks in electroacupuncture group. The sucrose preference test, forced swimming test, open field test, tail suspension test, elevated plus maze, Catwalk analysis, RNA sequencing, Nissl staining, Golgi staining, TUNEL staining, Edu labeling, and doublecortin staining were performed. Lymphocyte subsets in peripheral blood and the levels of IL-1β, IL-6, TNF-α, and expression of Iba1/CD86, Iba1/NLRP3, TLR4/p38/NF-κB/NLRP3 pathways in the hippocampus were detected. Electroacupuncture effectively protected against the development of depression-like symptoms. The number of granulosa cells and doublecortin-positive cells in the dentate gyrus (DG) were significantly decreased in PSD group, which were significantly upregulated ( P  < 0.01) by electroacupuncture. Electroacupuncture also significantly reduced ( P  < 0.05) TUNEL-positive cells in the DG and CA1. RNA-seq revealed that electroacupuncture may exert antidepressant effect by regulating the inflammation mediated by TLR4/NF-κB/NLRP3 pathway in hippocampus. Electroacupuncture remarkably elevated ( P  < 0.01) the ratio of CD4+ to CD8+ T cells and percentage of CD3-CD49b+ cells in CD45+CD49b+ cells in the peripheral blood. Electroacupuncture significantly reduced ( P  < 0.05) the high levels of IL-1β, IL-6, TNF-α, iba1, TLR4, p-p38, p-NF-κB, and NLRP3 and sedentary behavior. Electroacupuncture was observed to mitigate depression symptoms and increase hippocampal neurogenesis in mice with PSD, possibly by inhibiting TLR4/p38/NF-κB/NLRP3 pathways and improving the microglia-mediated inflammatory microenvironment in the hippocampus.

Emotional information can be seen everywhere in daily life. Research on emotional words often employs lexical decision tasks to judge the veracity of words, involving only superficial processing and not the deep processing of emotional significance. Therefore, the purpose of this study is to explore the effect of types of emotional words on the processing of emotional pictures. Participants were publicly recruited for a button-press experiment to discuss the impact of emotional words on the processing of emotional pictures from both behavioral and physiological mechanisms. The results of experiment 1 show: (a) in terms of reaction time, the processing speed for negative emotional words was slower, with longer reaction times; (b) In terms of accuracy, positive emotional words had a higher correct rate than negative emotional words. The results of experiment 2 found: (a) a significant main effect of emotional word type in the late processing stage; (b) a significant interaction between emotional word type and congruency. Previously presented emotional words affect the processing of subsequently presented emotional pictures, with differences in the processing of the four types of words, indicating a significant role of language in emotional processing.

This study aimed to elucidate the effects of sucrose (SUC) consumption on neurodevelopmental processes through behavioral changes in rodents and determine whether these effects could be because of sweet taste, energy supply, or both. Mice were divided into five groups based on the time of SUC or sucralose (SUR, a noncaloric sweetener) administration: for 6 days from gestation day (GTD) 7, to birth from GTD13 and for 15 days from postnatal day (PND) 21, PND38, and PND56. SUC and SUR administration did not impact body weight. However, food intake in the PND56 group and water intake in the GTD13 and PND56 groups were increased by SUC and SUR administration. Amphetamine (0.5, 1, 2, and 3 mg/kg), a dopamine reuptake inhibitor, administration to assess alterations in the dopaminergic system induced increases in distance traveled after SUC administration in the GTD13 and PND21 groups compared with that in the control (vehicle administration) group. In contrast, the SUR group showed a decrease in the distance traveled in the PND56 group. Although there were no differences in locomotor activity and foraging behavior, SUC preference increased in the SUC group regarding the GTD13 and PND38 groups. The correlations between SUC preference and foraging behavior and between SUC preference and amphetamine response varied in both groups according to the developmental stage. Excessive SUC consumption might affect neural function at different developmental stages, as it could affect brain function through complex mechanisms involving sweet taste and energy supply and influence the dopaminergic system.

We investigated differences in subcortical white matter according to the presence disorders of consciousness (DOC) in patients with hypoxic-ischemic brain injury (HI-BI), using tract-based spatial statistics (TBSS). Thirty-two consecutive patients with HI-BI were recruited. The patients were assigned in group A [preserved consciousness (Glasgow Coma Scale: 15 and Coma Recovery Scale-revised (CRS-R): 23, 9 patients)] or group B [DOC present (Glasgow Coma Scale <15 and CRS-R < 23, 20 patients)]. Voxel-wise statistical analysis of fractional anisotropy data was performed by using TBSS as implemented in the FMRIB Software Library. We calculated mean fractional anisotropy values across the white matter skeleton and within 48 regions of interest (ROIs) based on intersections between the skeleton and the probabilistic Johns Hopkins University white matter atlases. Among the 48 ROIs examined, the fractional anisotropy values of two ROIs (the left superior corona radiata, and left tapetum) were significantly lower in group B than in group A ( P  < 0.05). No significant differences were observed, however, in the other 46 ROIs ( P  > 0.05). Our results suggest that abnormalities of the superior corona radiata and tapetum may be critical for DOC presence in patients with HI-BI.

This study aimed to investigate the effects of rolipram, a phosphodiesterase inhibitor, on brain tissue regeneration. Trimethyltin-injected mice, an animal model of hippocampal tissue regeneration, was created by a single injection of trimethyltin chloride (2.2 mg/kg, intraperitoneally). Daily rolipram administration (10 mg/kg, intraperitoneally) was performed from the day after trimethyltin injection until the day before sampling. In Experiment 1, brain samples were collected on day 7 postinjection of trimethyltin following the forced swim test. In Experiment 2, bromodeoxyuridine (150 mg/kg, intraperitoneally/day) was administered on days 3-5 and sampling was on day 21 postinjection of trimethyltin. Samples were routinely embedded in paraffin and sections were obtained for histopathological investigation. In Experiment 1, rolipram-treated mice showed shortened immobility times in the forced swim test. Histopathology revealed that rolipram treatment had improved the replenishment of neuronal nuclei-positive neurons in the dentate gyrus, which was accompanied by an increase in the percentage of phosphorylated cyclic AMP response element-binding protein-positive cells. In addition, rolipram had decreased the percentage of ionized calcium-binding adapter protein 1-positive microglia with activated morphology and the number of tumor necrosis factor-alpha-expressing cells. In Experiment 2, double immunofluorescence for bromodeoxyuridine/neuronal nuclei revealed an increase of double-positive cells in rolipram-treated mice. These results demonstrate that rolipram effectively promotes brain tissue regeneration by enhancing the survival of newborn neurons and inhibiting neuroinflammation.

To investigate the role of JAK2/STAT3 signaling pathway in neural function recovery in rats with spinal cord injury (SCI) after treadmill training. Sprague-Dawley rats were randomly divided into four groups: (a) sham group; (b) SCI group; (c) SCI+treadmill training group (SCI/TT); and (d) SCI/TT+AG490 group (a JAK2 inhibitor) ( n  = 12). The 12 Sprague-Dawley rats in each group were randomly assigned into 1 st , 3 rd , 7 th , and 14 th  day subgroups. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to assess the spinal cord function, and JAK2, STAT3, and IL-6 protein expressions in the rat spinal cord were evaluated by western blot. The level of cell apoptosis and expressions of apoptotic proteins were evaluated by TUNEL assay and immunohistochemistry, respectively. Rats in the SCI+TT group showed a significantly higher BBB score after SCI compared with the SCI group and the SCI/TT+AG490 group. Mechanistically, the JAK2/STAT3 signal pathway was immediately activated after SCI compared with sham group, and JAK2 and STAT3 were obviously upregulated when treadmill training was performed ( P  < 0.05). Results of TUNEL assay showed that the apoptotic rate in SCI/TT was significantly lower than that in the SCI group and SCI/TT+AG490 group ( P  < 0.05). Besides, the IL-6 expression in the SCI/TT group was significantly attenuated compared with the SCI group ( P  < 0.05). Our results showed that physical treadmill training can enhance activation of JAK2/STAT3 signal pathway and attenuate apoptosis in the injured spinal cord, resulting in better functional recovery. These results underline the importance of synergistic treatment strategies for SCI.