Increased susceptibility of mice obtained from in vitro fertilization to global cerebral ischemia-reperfusion injury: possible role of hydrogen sulphide and its biosynthetic enzymesLi, Hong; Liu, Lijun; Dang, Minyan; Zhang, Wenzhi; Liu, Jie
doi: 10.1080/00207454.2019.1667797pmid: 31516045
AbstractAim of the Study: This study was designed to explore the relative susceptibility of in vitro fertilization (IVF)-conceived mice to global cerebral ischemic injury with the possible role of hydrogen sulphide and enzymes responsible for its production.Materials and Methods: IVF was carried to obtain pups, which were allowed to grow to the age of eight weeks. Thereafter, male mice were subjected to 20 min of global ischemia and 24 h of reperfusion. The mice obtained from other groups including normal mating, superovulation but normal mating and normal mating but embryo implantation were also subjected to global ischemia-reperfusion (I/R) injury.Results: IVF-derived mice exhibited significant more injury in response to I/R injury in comparison to other groups assessed in terms of impairment in locomotor activity, development of motor in coordination, neurological severity score, cerebral infarction and apoptosis markers (caspase-3 activity and Bcl-2 expression). Moreover, there was a relative decrease in the brain levels of hydrogen sulphide (H2S) and its biosynthetic enzymes viz. cystathionine-β-synthase and cystathionine-γ-lyase. Interestingly, the levels of H2S and cystathionine-γ-lyase were significantly low in IVF-derived mice in basal conditions also, i.e. before subjecting to I/R injury and these biochemical alterations were associated with the behavioural deficits in mice, even before subjecting to I/R injury.Conclusion: It is concluded that in vitro fertilization-derived mice are more susceptible to global cerebral I/R injury, which may be possibly due to decreased levels of hydrogen sulphide and its biosynthetic enzymes viz., cystathionine-β-synthase and cystathionine-γ-lyase.
Endurance and resistance training mitigate the negative consequences of depression on synaptic plasticity through different molecular mechanismsKang, Jie; Wang, Youhua; Wang, Di
doi: 10.1080/00207454.2019.1679809pmid: 31847639
AbstractPurpose/aim of the study: To investigate the effect and molecular mechanism of endurance and resistance training on synaptic plasticity in chronic stressed depression rats.Materials and methods: Chronic unpredictable mild stress (CUMS) was used to establish depressive rats model. Healthy male SD rats were randomly divided into 4 groups (control, CUMS, AE, and RT). The animals in AE and RT groups were respectively subjected to continuous treadmill running and intermittent weight-bearing treadmill training for 8 weeks after CUMS. Forced swimming test (FST) was used to evaluate behavior of rats. The flow cytometry was used to detect the hippocampal neuronal apoptosis. LTP in hippocampal CA1 region were analyzed by electrophysiology. The expressions of various mRNA and proteins related to synaptic function were measured using RT-PCR, Western blot or immunohistochemistry in the hippocampus.Results: Results shown that rats exhibited depressive behavior after CUMS stimulation, specifically immobility time was increased and swimming time and climbing time were reduced in rats during FST. After training, AE and RT all attenuated CUMS-induced depressive behavior of rats. AE and RT reduced apoptosis rate of hippocampal neuron and increased PS amplitude and fEPSPs slope after CUMS stimulation. After CUMS stimulation, AE promoted mRNA expressions, including BDNF, mTOR, TrkB, Syn, Syp, CaMKIIβ, and DRD5, and increased protein expressions, including IGF-1, PGC-1α, ERRβ, and FNDC5. While RT promoted mRNA expressions, including IGF-1, mTOR, Akt, Syn, and Syp, and improved protein expressions, including IGF-1, IGF-1R, and p-Akt.Conclusions: In conclusion, AE and RT for 8 weeks improved CUMS-induced depressive behavior, neuron injury and synaptic plasticity through regulating different signaling pathways.
Effects of glutamate-related drugs on anxiety and compulsive behavior in rats with obsessive-compulsive disorderZhan, Yuhua; Xia, Jing; Wang, Xumei
doi: 10.1080/00207454.2019.1684276pmid: 31680595
AbstractObjective: Altered glutamatergic neurotransmission has been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). We examined the effects and potential mechanism of glutamate-related drugs on compulsive behavior in quinpirole (QNP)-sensitized rats, to deepen our understanding of the link between OCD and glutamate.Method: This study systematically compared the effects of the partial NMDA agonist D-Cycloserine and the NMDA antagonist NVP-AAMO77, Ro25-6981 on compulsive behavior using the elevated zero maze, open field, and marble burying tests in QNP-induced OCD model.Results: The competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists NVP-AAMO77 (5 mg/kg) and Ro25-6981 (5 mg/kg) significantly inhibited anxiety-like and compulsive behavior in rats. And D-Cycloserine at all doses showed significant suppression on anxiety-like and marble-burying behavior. Glutamic acid (Glu) levels, reflecting changes in the glutamatergic neurotransmission, were significantly decreased in rat hippocampus of the NVP-AAMO77 and D-Cycloserine-treated group compared to the saline-treated group. The levels of other amino acids were unaffected. Moreover, NVP-AAMO77 significantly decreased the expression of the subunit NR2A of the NMDAR, and Ro25-6981 suppressed the level of the subunit NR2B of the NMDAR, while D-Cycloserine decreased both the subunit NR2A and NR2B of the NMDAR.Conclusion: Collectively, these findings suggest a functional role of NMDARs in anxiety and compulsive behaviors, with NMDARs inhibition promoting anxiolytic-like and anti-compulsive responses. These findings suggest that D-cycloserine, NVP-AAMO77, and Ro25-6981 could be useful drugs for the treatment of OCD, which may be due to the suppression of NR2A- or NR2B- containing NMDAR.
Neuroprotective effects of mitoquinone and oleandrin on Parkinson’s disease model in zebrafishÜnal, İsmail; Çalışkan-Ak, Esin; Üstündağ, Ünsal V.; Ateş, Perihan S.; Alturfan, Ahmet A.; Altinoz, Meric A.; Elmaci, Ilhan; Emekli-Alturfan, Ebru
doi: 10.1080/00207454.2019.1698567pmid: 31771386
AbstractAim: The aim of this study is to investigate the possible protective effects of mitoquinone and oleandrin on rotenone induced Parkinson’s disease in zebrafish. Materials and methods: Adult zebrafish were exposed to rotenone and mitoquinone for 30 days. Biochemical parameters were determined by spectrophotometric method and Parkinson’s disease-related gene expressions were determined by reverse transcription polymerase chain reaction method. Measurement of neurotransmitters was performed by liquid chromatography tandem-mass spectrometry instrument. The accumulation of synuclein was demonstrated by immunohistochemical staining. In vitro thiazolyl blue tetrazolium bromide method was applied to determine the mitochondrial function of synaptosomal brain fractions using rotenone as a neurotoxic agent and mitoquinone and oleandrin as neuroprotective agents. Results: Mitoquinone improved the oxidant-antioxidant balance and neurotransmitter levels that were disrupted by rotenone. Mitoquinone also ameliorated the expressions of Parkinson’s disease-related gene expressions that were disrupted by rotenone. According to thiazolyl blue tetrazolium bromide assay results, mitoquinone and oleandrin increased mitochondrial function which was decreased due to rotenone exposure. Conclusion: Based on the results of our study, positive effects of mitoquinone were observed in Parkinson’s disease model induced by rotenone in zebrafish.
Utilizing wavelet deep learning network to classify different states of task-fMRI for verifying activation regionsGui, Shanquan; Gui, Renzhou
doi: 10.1080/00207454.2019.1698568pmid: 31778088
AbstractPurpose: We propose a convolutional neural network (CNN) based on wavelet for verifying the activation regions decided with statistical analysis. Because the functional magnetic resonance imaging (fMRI) data contains lots of noises, it is difficult to get the data of blood-oxygen-level dependent (BOLD) signal directly for intervention testing like animal studies. So it is difficult to effectively verify these activation regions. Based on the rapid development of deep learning technology. Materials and methods: We select the task fMRI data of presenting food and nonfood pictures to volunteer subjects from open public data, whose website is https://www.openfmri.org/dataset/ds000157/. Firstly, the brain activation regions are obtained by utilizing the method of statistical analysis. Then the spatial coordinates are acquired from the activation regions by checking the atlas table. The P-value of the activation regions are less 0.05. The activation regions are the most responsive to perceive the differences of BOLD in the brain between the two states, presenting food and nonfood pictures. We select the part task fMRI data of from the activation regions, for preparing the training and validation samples. Then we design a deep leaning network based on wavelet to classify the task fMRI data between food and nonfood.Results and conclusions: The classification accuracy is 80.23%. However, when we select the spatial coordinates of other inactivation regions, the classification accuracy is only 60%. The differences of classification accuracy between the activation regions and the inactivation regions prove that the activation regions selected with statistical analysis method are accurate and effective. The two methods of deep learning and statistical analysis can be cross-validated for the study of human being brain.
Co-treatment of vitamin D supplementation and aerobic training improves memory deficit in ovariectomized ratBabaei, Parvin; Damirchi, Arsalan; Hoseini, Zahra; Hoseini, Rastegar
doi: 10.1080/00207454.2019.1699082pmid: 31775548
AbstractObjective: Metabolic syndrome (MetS) and insufficient vitamin D levels are globally increasing phenomena which are correlated with cognitive impairment. This study investigated the interactive effect of aerobic training with vitamin D supplementation on memory deficit in rats with metabolic syndrome induced by ovariectomy.Methods: A total of forty Wistar rats weighing 240–255 gr were randomly matched on their body weight and divided into ovariectomy (OVX, n = 32) and sham-operated (SHAM; n = 8) groups. OV group was then divided into vitamin D supplementation (OVX + Vit D; 10000 IU/kg/week, for 8 weeks, n = 8), aerobic training (OVX + AT; n = 8), aerobic training and vitamin D supplementation (OVX + AT + Vit D; 10000 IU/kg/week, for 8 weeks, n = 8), and vehicle control group receiving sesame oil (OVX + Ses Oil; n = 8). After the end of intervention, passive avoidance learning and memory were assessed in step through passive avoidance paradigm. Obtained data were analyzed by ANOVA and post hoc Tukey test.Results: After 8 weeks of aerobic training and vitamin D supplementation, step through dark compartment latency (STL) was significantly higher and total time spent in that compartment (TSD) was lower in OVX + AT + Vit D compared to the other counterpart groups.Conclusion: Vitamin D supplementation combined with 8-week aerobic training alleviates cognitive impairment metabolic syndrome induced by ovariectomy.
The effects of minocycline on proliferation, differentiation and migration of neural stem/progenitor cellsShamsi, Fatemeh; Zeraatpisheh, Zahra; Alipour, Hamed; Nazari, Abbas; Aligholi, Hadi
doi: 10.1080/00207454.2019.1699083pmid: 31801401
AbstractPurpose: There are several attempts to enhance the capacities of neural stem/progenitor cells (NS/PCs) as a probable source of stem cell therapy for neurodegerative diseases. The evidence shows that minocycline has several non-antibacterial effects in neurodegenerative diseases. We aimed to investigate the effect of minocycline on proliferation, differentiation and migration of embryonic NS/PCs.Materials and methods: NS/PCs extracted from ganglionic eminence of 13.5-day embryonic mice were cultured according to neurosphere protocol. After second passage they were exposed to different doses of minocycline for 7 days. The number and diameter of neurospheres were assessed to evaluate their proliferation. Migration was estimated based on the distances traveled by the cells. Because of the importance of NS/PCs behaviors in 3-dimentional environment, all assessments were done in 3-dimentional and 2-dimentional cultures. Moreover, the fate of NS/PCs to neuron or glial cells was studied.Results: NS/PCs exposed to 1 μg/ml and 10 μg/ml of minocycline and those in untreated group traveled significantly longer distances compared to those treated with 50 μg/ml and 100 μg/ml of minocycline. In addition, higher doses of minocycline reduced the NS/PCs proliferation remarkably compared to control condition just in 2-D culture. However, the differentiation capacity of cells was not significantly affected by 1 and 10 μg/ml of minocycline.Conclusion: The behavior of NS/PCs depends on minocycline dose as well as the characteristics of environment.
Prediction and analysis of weighted genes in isoflurane induced general anesthesia based on network analysisChen, Yue; Zhou, Zhen-Feng; Wang, Yu
doi: 10.1080/00207454.2019.1701452pmid: 31801399
abstractPurpose: Isoflurane is still wildly used in the developing countries and isoflurane-induced general anesthesia gives rise to serious side effects. The aim of the present study was to investigate the molecular mechanism on isoflurane-induced general anesthesia.Materials and methods: The microarray data of GSE64617 dataset was downloaded from Gene Expression Omnibus (GEO) database. A total of 755 DEGs were identified using the limma package in the R programming language. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes, and Genomes (KEGG) pathways enrichment were conducted for DEGs. A protein-protein interaction (PPI) network was constructed for DEGs and sensory perception related genes. A global miRNA-mRNA regulatory network was constructed to reveal the interactions in miRNA and mRNA in isoflurane treated samples. Degree was used to evaluate the importance of a gene in the PPI network and miRNA-mRNA regulatory network.Results and conclusions: HMBOX1, CSNK2A1, PNN, SRRM1, PRPF40A, APCNTRK1, MAPK1, hsa-miR-16-5p, hsa-miR-424-5p, hsa-miR-497-5p and hsa-miR-17-5p were selected as weighted genes. The expression changes were further vitrificated in the rat models by performing quantitative real-time PCR (qPCR) analysis. In conclusion, we find several weighted mRNAs and miRNAs involved in isoflurane induced general anesthesia through bioinformatics analysis.