Open Field Test Research Articles

A single injection of neuropeptide QRFP in the lateral hypothalamus decreased food intake.

Severe eating disorders, such as obesity, bulimia, and anorexia, keep increasing to epidemic proportions worldwide. Understanding of neuropeptides' role in complex hunger/satiety mechanisms may allow new prospects for treatment and prevention. Pyroglutamylated arginine-phenylalanine-amide peptides (QRFPs) are thought to enhance feeding following the central administration. In our study, QRFP-26 was delivered into the lateral hypothalamic area of male Wistar rats by direct microinjections, as QRFP-26 expressing neurons and binding sights are densely present in this neural structure. The consumption of liquid food was measured over 60-min. Both doses (100 and 200 ng) significantly decreased food intake compared to the control treatment. Neuropeptide Y Y1R/NPFF (neuropeptide FF) antagonist BIBP3226 eliminated the anorexigenic effect caused by QRFP-26 administration. QRFP-26 affects neither general locomotion, behavioral patterns examined in the Open Field Test, nor anxiety. This study is the first to report the anorexigenic action of QRFP-26 following direct administration into the hypothalamus, emphasizing steady locomotion and anxiety levels. We have shown that the effect of QRFP can be linked to the neuropeptide Y (NPY) Y1 or NPFF receptors.

Impaired hippocampal neurogenesis associated with regulatory ceRNA network in a mouse model of postoperative cognitive dysfunction

BackgroundPostoperative cognitive dysfunction (POCD) represents a post-surgical complication that features progressive cognitive impairment and memory loss, often occurring in elderly patients. This study aimed to investigate the potential biological mechanisms underlying POCD.MethodsMale C57BL/6 mice (2 and 17 months old) were randomly assigned to surgery or control groups. The surgery group underwent laparotomy under 1.5% isoflurane anesthesia, while controls received no intervention. Cognitive function was assessed 7–10 days post-surgery using open field, Y-maze, and novel object recognition tests.Hippocampal mRNA expression was analyzed using Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. A competing endogenous RNA (ceRNA) network was constructed using microRNA (miRNA) target prediction databases (miRanda, miRTarbase, miRcode) and sequencing results. Key findings were validated by RT-qPCR and immunofluorescence. The Connectivity Map (CMap) database was queried to predict potential POCD treatments.ResultsAging significantly affected mice’s spontaneous activity in the open field test (F1, 28 = 8.933, P < 0.01) and the proportion of time spent in the center area (F1, 28 = 5.387, P < 0.05). Surgery significantly reduced the rate of spontaneous alternations in the Y-maze (F1, 28 = 16.94, P < 0.001) and the recognition index in novel object recognition test (F1, 28 = 6.839, P < 0.05) in aging mice, but had no effect on young mice. Transcriptome analysis revealed that aging and surgery downregulated multiple neurogenesis-related genes in the hippocampus. Doublecortin (DCX) immunofluorescence staining confirmed reduced hippocampal neurogenesis in aging mice, which was further decreased after surgery. We identified several key lncRNAs and miRNAs implicated in neurogenesis regulation. Additionally, drugs were predicted as potential therapeutic candidates for POCD treatment.ConclusionBoth aging and surgery have complex effects on the hippocampal transcriptome in mice. The significant decrease in neurogenesis may be a potential reason for the increased susceptibility of aging mice to POCD. The identified key regulatory lncRNAs, miRNAs, and drugs provide potential therapeutic targets for POCD prevention and treatment.

Dietary Capsaicin Exacerbates Gut Microbiota Dysbiosis and Mental Disorders in Type 1 Diabetes Mice

Background/Objectives: Diabetes mellitus is often accompanied by mental health complications, including anxiety, depression, and cognitive decline. Recent research suggested that capsaicin, the active component of chili peppers, may influence mental health. This study aimed to determine the effect of dietary capsaicin on mental disorders in a type 1 diabetes (T1D) mouse model, while also exploring the potential involvement of the microbiota-gut-brain axis. Methods: We induced T1D in mice using streptozotocin (STZ) and administered a diet supplemented with 0.005% capsaicin for five weeks. Behavioral assessments, including the open field test (OFT), tail suspension test (TST), forced swimming test (FST), elevated plus maze (EPM) test, and Morris water maze (MWM) test, were conducted to evaluate depressive and anxiety-like behaviors as well as cognitive function. Targeted and untargeted metabolomics analyses were performed to assess neurotransmitter levels in the hippocampus and serum metabolites, while 16S rRNA sequencing was utilized to analyze gut microbiota composition. Intestinal barriers were determined using western blot detection of the tight junction proteins ZO-1 and occludin. Results: Dietary capsaicin exacerbated anxiety and depressive-like behaviors along with cognitive declines in T1D mice. Capsaicin reduced gut microbiota diversity and levels of beneficial bacteria, while broad-spectrum antibiotic treatment further intensified anxiety and depression behaviors. Metabolomic analysis indicated that capsaicin disrupted metabolic pathways related to tryptophan and phenylalanine, leading to decreased neuroprotective metabolites, such as kynurenic acid, hippurate, and butyric acid. Additionally, capsaicin diminished the expression of ZO-1 and occludin, indicating increased intestinal permeability. Conclusions: Dietary capsaicin aggravates gut microbiota and metabolic disturbances in diabetic mice, thereby worsening anxiety, depression, and cognitive decline.

Olfactory deprivation promotes amyloid β deposition in a mouse model of Alzheimer's disease.

Olfactory dysfunction is regarded as an early marker for Alzheimer's disease (AD). Slowly progressing AD pathology is interpreted to impair olfactory sensation and cognition independently, while olfactory deficits emerge earlier. The present experiments tested the possibility that olfactory impairment may worsen cognition or AD pathology using 3xTg AD model mice with olfactory bulbectomy (OBX). In open-field tests, OBX was shown to increase anxiety-like behavior in both wild-type (WT) and AD model mice, and hyperactivity was induced in WT mice only. Spatial memory, assessed by the Morris water maze (MWM) test, was impaired in WT but not AD mice. Object memory, assessed by the novel object recognition test, was not changed by OBX either in WT or AD mice. Densitometry of Aβ plaques stained with 6E10 and anti-Aβ42 antibodies was carried out in sections containing the hippocampal formation obtained from AD mice aged 12 and 18 months. The plaque area was larger in the OBX than in the sham group at 12 months. At 18 months, there was also difference in the plaque area. Given that Aβ plaques emerge in 3xTg mice relatively later (>9 months of age) than in other models, OBX in 3xTg mice appears to exacerbate Aβ pathology at the early phase of Aβ emergence, implying a causative link of smell loss to AD pathogenesis. The accelerated Aβ plaque formation by OBX was accompanied by microglial activation. Early intervention to smell loss may be beneficial for AD control.

Protective and Therapeutic Effects of Orlistat in Combination with Elettaria cardamomum “Cardamom” Extract on Learning, Memory, Anxiety, and Neuroinflammation in Obese Mice

Introduction and Objective: Obesity has increased worldwide, and existing anti-obesity medications have treatment limitations that diminish their overall benefits. This study aimed to investigate the effects of orlistat in combination with Elettaria cardamomum “Cardamom” (CAR) extract on working memory, recognition memory, anxiety, and inflammation within hippocampal tissue. Methods: Mice were categorized into two groups: a control group (CD) and a cafeteria diet (CAF) group induced with obesity (CAF) for 10 weeks. The groups were then subdivided into a CAF group treated with orlistat (CAF-ORL), a CAF group treated with orlistat and Elettaria cardamomum (CAF-ORL-CARD), and a group that continued on the CAF. The CAF-ORL group received orlistat at a dosage of 10 mg/kg/day for four weeks, while the CAF-ORL-CARD group received 10 mg/kg/day of orlistat and 500 mg/kg of CAR extract via oral gavage. In the 14th week, various assessments were conducted, including the novel object recognition (NOR) test, Y maze test, marble-burying test (MBT), open-field test, and TNF-α levels in the hippocampus. Result: TNF-α levels in the hippocampal tissue of the CAF group were elevated compared to the CD group (p &lt; 0.01), whereas the CAF-ORL group exhibited reduced TNF-α levels compared to the CAF group (p &lt; 0.01). Moreover, TNF-α levels in the CAF-ORL-CARD group were significantly lower than in the CAF-ORL group (p &lt; 0.01). The recognition index was notably higher in the CAF-ORL group compared to the CAF group (p &lt; 0.01) and higher in the CAF-ORL-CARD group compared to the CAF-ORL group (p &lt; 0.01). However, there were no changes in the open-field test and Y maze test (p &gt; 0.05). Conclusions: Orlistat combined with CAR has positive effects on neuroinflammation and memory, suggesting that this combination may offer potential therapeutic benefits for cognitive impairments and hippocampal dysfunction associated with obesity.

Exosomal PINK1 from Human Umbilical Cord Mesenchymal Stem Cells Attenuates Neurological Deficits and Inflammatory Responses after Intracerebral Hemorrhage in Mice.

This study investigated the therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (huMSCs), focusing on PTEN-induced kinase 1 (PINK1) and its impact on exosome efficacy. Postmodification, exosomes were administered to a murine model of intracranial hemorrhage (ICH). Assessments included brain edema, neurological function, anxiety-like behaviors, inflammatory responses, and microglial polarization. We observed that administration of exosomes from control huMSCs significantly reduced brain water content, indicating a reduction in brain edema, as quantitatively assessed through water content analysis. Neurological function, evaluated using a standard scoring system, showed marked improvement in animals treated with control exosomes compared with those receiving PINK1-deficient exosomes, highlighting the importance of PINK1 in mediating neurological recovery. Additionally, control exosomes substantially decreased anxiety-like behaviors in the Open Field Test, demonstrated by reduced immobility times and increased exploratory behavior. Inflammatory response assessments showed a favorable shift with decreased levels of pro-inflammatory cytokines (MCP-1, IL-1β, TNF-α) and increased levels of the anti-inflammatory cytokine IL-10 in the exosome-treated groups. Furthermore, analysis of microglial polarization revealed a shift toward the anti-inflammatory M2 phenotype, evidenced by decreased M1 markers (Cd86, Iba1) and increased M2 markers (Arg1, Cd206) in the control exosome-treated group. Taken together, we found that PINK1-deficient exosomes showed reduced therapeutic efficacy in ICH treatment compared with the exosomes with normal PINK1 expression. Our findings underscore the critical role of PINK1 in enhancing the therapeutic potential of huMSC-derived exosomes in ICH treatment.

Baihe Dihuang Tang as a therapeutic candidate for insomnia: Targeting gut dysbiosis and neuroendocrine dysfunction

AbstractBaihe Dihuang Tang (BDT), is a traditional Chinese medicinal formulation historically utilized to manage various health conditions, including insomnia. This therapeutic use of BDT for treating insomnia is rooted in its potential to regulate the gut microbiota, neuroendocrine, and serotonin systems, which may collectively contribute to its effectiveness. This study aims to explore the anti‐insomnia effects of BDT, and focus on its underlying mechanisms, emphasizing the potential interplay with gut microbiota, neuroendocrine, and serotonin pathways. An insomnia mouse model was induced using p‐chlorophenylalanine (PCPA). Subjects received varying doses of BDT or a saline solution as a control. Behavioral assessment was conducted via the open field test and elevated plus maze test. Hypothalamic monoamine neurotransmitter levels were quantified using ELISA kits. Neurosteroid levels in brain and serum samples were determined through high‐performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS). Gut microbiota composition was evaluated using 16S rRNA amplicon sequencing. PCPA‐induced insomnia led to significant alterations in neurosteroids, monoamine neurotransmitters, and gut microbiota composition. BDT treatment markedly improved behavioral parameters in insomniac mice, evidenced by enhanced motility and reduced sleep latency compared to controls. BDT administration restored neurosteroid and monoamine neurotransmitter dose‐dependently, suggesting potential for neuroendocrine system homeostasis restoration. BDT‐treated mice exhibited significant gut microbiota composition changes, including reduced Acidobacteria, increased Fusobacteria and Firmicutes at the phylum level, and decreased Alistipes at the genus level, compared to the insomnia model group. BDT effectively rectifies gut dysbiosis and mitigates neuroendocrine and serotonin system dysfunctions induced by insomnia, emerging as a promising therapeutic candidate for insomnia management.

Accuracy of PVSyst Simulations in the Reproduction of the Yield Performance of Multicrystalline, Monocrsytalline and Monocasting Modules in Outdoor Conditions

In this study we performed field tests on three small installations consisting of 12 modules each and next to each other, all of them using exactly the same manufacturing technology for cells and modules and employing the same manufacturing equipment and raw materials. The only difference between the systems was the wafer technology used. Two of them were manufactured through the same casting technology (Direct solidification system-DSS) and the same equipment: in one of them we grew mc-Si and in the other one CM-Si (mono casting). In the third system we used traditional Czochralski monocrystalline wafers as technology. Two of the facilities (the DSS based ones) have been closely monitored for three years, and the traditional monocrystalline one for 17 months. For the three installations the performance data is shared and compared with PVsyst simulations and correlated well to each other.

The effect of caffeine in a model of schizophrenia-like behavior induced by MK-801 in mice.

The blockade of NMDA receptors during early developmental stages is accepted as a model for schizophrenia-like behavior. This study aimed to investigate the effects of caffeine on adult behaviors in mice subjected to tests of schizophrenia-like behaviors induced by the NMDA receptor antagonist MK-801. MK-801 (0.25mg/kg, twice daily, 0.1mL/10g body weight, intraperitoneally) was administered to Balb/c mice during PND 7-10 to establish a schizophrenia-like behavior model. In one group, caffeine (10mg/kg, twice daily, 0.1mL/10g body weight, intraperitoneally) was given 30minutes after MK-801 administration. In another group, MK-801 was administered 30minutes after caffeine injection. At 8-10 weeks of age, behavioral tests were performed sequentially: open field test (OFT), elevated plus maze test (EPM), Morris water maze test (MWM), and social interaction test. MK-801 administration significantly increased anxiety-like behaviors and decreased exploratory behavior in the OFT by reducing the time spent in the center, the frequency of center entries, and rearing frequency, while increasing the latency to the first center entry. In the EPM, MK-801 significantly decreased the time spent in the open arms, the frequency of open arm entries, and the head-dipping behavior of the open arm while increasing the time spent in the closed arms and the latency to the first open arm entry. In the MWM, MK-801 impaired learning and memory performance. MK-801 reduced social interaction. Caffeine reversed the anxiety, social interaction, learning, and memory impairments caused by MK-801. MK-801 administration during the neonatal period induces schizophrenia-like behaviors in adulthood, whereas low-dose caffeine can mitigate these effects.

Assessment of neuroprotective potential of Cuscuta reflexa in aluminium chloride-induced experimental model of Alzheimer's disease: In vitro and in vivo studies.

Cuscuta reflexa (family Convolvulaceae), commonly known as giant dodder or Amarbel, is a parasitic plant that has garnered attention in pharmacological research due to its diverse bioactive compounds and potential therapeutic applications. Scientific studies have validated its traditional uses in folk medicine, highlighting its pharmacological activities. Alzheimer's Disease (AD) is a neurodegenerative disorder marked by the buildup of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT) in the brain, leading to synaptic impairment and the gradual loss of neurons. Currently, no effective medication is available to treat the development and progression of the disease. Hence, there is a rising concern about using alternative therapy such as herbal medicine to limit the progression of AD and improve the quality of a patient's life with minimum side effects. The plant Cuscuta reflexa has traditionally been claimed to possess neuroprotective effects but has not yet been validated scientifically. The present study aimed to investigate the potential of the hydroalcoholic extract of Cuscuta reflexa (CRE) to ameliorate the neurodegenerative effect of aluminium chloride (AlCl3) using in vitro and in vivo studies. The neuroprotective activity of CRE was evaluated using in vitro and in vivo experimental models of AlCl3-induced AD. The in vitro study showed that CRE markedly reduced AlCl3-induced cytotoxicity in PC12 cells. The in vivo study using the AlCl3-induced AD rat model showed that CRE treatment improved learning and memory, as evaluated using the open field test (OFT) and Morris water maze (MWM) test. CRE also showed the reduction in oxidative stress induced by AlCl3 in the brains of the rats by virtue of the significant decrease in oxidative stress biomarker malondialdehyde (MDA) and increase in the antioxidant parameters such as reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD). Further, CRE exhibited its cholinergic activity by lowering the AlCl3-induced enhanced levels of acetylcholinesterase (AChE) in the brains of rats. Histopathological analysis of the brains of rats showed that CRE treatment prevented the reactive changes and the damage in the neuronal tissue caused due to the AlCl3. Conclusively, CRE ameliorated AlCl3-induced neurobehavioural toxicity in the rat model of AD by virtue of its anti-inflammatory, antioxidant, cholinergic and neuroprotective effects which suggests its use in the treatment of progressive neural damage and cognitive deficits in AD patients.

Antiplatelet Therapy as a Novel Approach in Parkinson's Disease: Repositioning Ticagrelor to Alleviate Rotenone-Induced Parkinsonism via Modulation of ER Stress, Apoptosis, and Autophagy.

Cardiovascular diseases, such as myocardial infarction, ischemic stroke, and coronary heart ailments have been closely associated with Parkinson's disease (PD). Despite this established link, the potential neuroprotective impact of the potent antiplatelet agent ticagrelor (Tica) remains unexplored against PD. Thus, we hypothesized that Tica could be repurposed as a therapeutic agent against PD. Rotenone experimental model was adopted in Wistar male rats by administering rotenone subcutaneously on alternate days during a 21-day experimental period and treating a subset of rats with Tica orally for the last 11 consecutive days. The administration of Tica improved motor function (open field test, hanging wire test) and restored striatal histological features. Additionally, Tica opposed the rotenone effect and markedly obliterated the striatal α-synuclein content but enhanced the protein expression of tyrosine hydroxylase and dopamine content. On the molecular level, Tica inhibited striatal endoplasmic reticulum stress (ERS) as evidenced by the downregulation of the ER-resident transmembrane sensor inositol-requiring enzyme 1 alpha and its downstream molecular targets, TNF receptor-associated factor 2 and c-Jun N-terminal kinase, along with a reduction in caspase-3 activity. On the other hand, Tica augmented the autophagy machinery by upregulating the autophagosome markers Beclin-1 and light chain 3-II, while inhibiting the content of cathepsin D. Therefore, the current study is the first to accentuate the neuroprotective potential of Tica in a rat model of PD via modulating the crosstalk between ERS, apoptosis, and autophagy to represent a potential novel therapeutic candidate for managing PD, particularly in patients with or prone to cardiovascular diseases.

IGF1 enhances memory function in obese mice and stabilizes the neural structure under insulin resistance via AKT-GSK3β-BDNF signaling.

Obesity is a prevalent metabolic disorder linked to insulin resistance, hyperglycemia, increased adiposity, chronic inflammation, and cognitive dysfunction. Recent research has focused on developing therapeutic strategies to mitigate cognitive impairment associated with obesity. Insulin growth factor-1 (IGF1) deficiency is linked to insulin resistance, glucose intolerance, and the progression of obesity-related central nervous system (CNS) disorders. In this study, we investigated the neuroprotective effects of IGF1 in two obesity models: diet-induced obesity (high-fat diet mice) and genetic obesity (ob/ob mice which is genetically deficient in leptin), and in vitro Neuro2A neuronal cells and primary cortical neurons under insulin resistance conditions. We performed RNA sequencing analysis using the cortex of high-fat diet mice injected with IGF1. Also, we detected cytokine levels in blood of high-fat diet mice injected with IGF1. In addition, we conducted the Barnes maze test as a spatial memory function test and open field test as an anxiety behavior test in ob/ob mice. We measured the levels of proteins and mRNAs related to insulin signaling, including synaptic density proteins in brain cortex of ob/ob mice. Our results showed that IGF1 injection enhanced spatial memory function and synaptic plasticity in obese mice. Furthermore, in vitro data demonstrated that IGF1 treated neurons revealed enhanced neural complexity and improved neurite outgrowth under insulin resistance condition through the AKT-GSK3β-BDNF pathway related to antidepressant, cognitive function and anti-apoptotic mechanisms. Therefore, our results provided that IGF1 have potential to alleviate cognitive impairment by promoting synaptic plasticity and neural complexity in the obese brain.

Juvenile chronic social defeat stress reduces prosocial behavior in adult male mice

Exposure to stress in early life can have a significant impact on individuals. However, the effects of early-life stress (ELS) on prosocial behavior remain unclear, as do the underlying mechanisms. In this study, ICR juvenile mice were subjected to juvenile chronic social defeat stress (jCSDS) between postnatal days 32 and 41, during which body weight changes were continuously monitored. The behaviors of adult mice were evaluated using the open field test (OFT), the social interaction test (SIT), and the prosocial choice task (PCT). ELISA was used to quantify serum levels of oxytocin, serotonin, and dopamine. The density of dendritic spines in the basolateral amygdala was evaluated by Golgi staining. Behavioral test results showed that jCSDS induced anxiety-like behavior and decreased prosocial selection tendency in mice. Additionally, exposure to jCSDS increased the serum levels of oxytocin, decreased those of serotonin, and increased the density of dendritic spines in the basolateral amygdala. Correlation analysis indicated that prosocial behavior was negatively correlated with serum oxytocin levels and dendritic spine density in the basolateral amygdala. These results suggested that jCSDS reduced prosocial behavior, possibly due to changes in serum oxytocin contents and adaptive changes in amygdaloid neurons.

Anxiety-like behavior and altered hippocampal activity in a transgenic mouse model of Fabry disease.

Fabry disease (FD) patients are known to be at high risk of developing neuropsychiatric symptoms such as anxiety, depression and cognitive deficits. Despite this, they are underdiagnosed and inadequately treated. It is unknown whether these symptoms arise from pathological glycosphingolipid deposits or from cerebrovascular abnormalities affecting neuronal functions in the central nervous system. We therefore aimed to fill this knowledge gap by exploring a transgenic FD mouse model with a combination of behavior, transcriptomic, functional and morphological assessments, with a particular focus on the hippocampus. Male FD mice exhibited increased anxiety-like behavior in the open field test, accompanied by a reduced exploratory drive in the Barnes maze, which could be related to the increased deposition of globotriaosylceramide (Gb3) identified in the dentate gyrus (DG). Hippocampus single-cell sequencing further revealed that Gb3 accumulation was associated with differential gene expression in neuronal and non-neuronal cell populations with granule, excitatory and interneurons, as well as microglia and endothelial cells as the main clusters with the most dysregulated genes. Particularly FD hippocampal neurons showed decreased electrical baseline activity in the DG and increased activity in the CA3 region of acutely dissected hippocampal slices. Our study highlights transcriptional and functional alterations in non-neuronal and neuronal cell clusters in the hippocampus of FD mice, which are suggested to be causally related to anxiety-like behavior developing as a consequence of FD pathology in mouse models of the disease and in patients.

Application and simulation of IEC water chillers for summer free cooling in data centers

Free cooling is regarded as the most effective way to reduce the energy consumption of the cooling system in data centers. This study proposes a novel water-medium indirect evaporative cooling (IEC) chiller used in a data center to achieve free cooling throughout the year as an alternative to electrical chillers. Field tests and numerical modeling of the IEC water chillers are both reported to evaluate the performance and efficiency. This paper first-time reports on the application of IEC water chillers to deliver year-round free cooling for a data center in Changji, China. The wet-bulb efficiency of the tested chiller is measured as 120% to 152.8% and the dew-point efficiency is 27% to 62.7%. A numerical model is established to verify the operating conditions, and some common operational optimizations are pointed out in this test for energy savings. PUE can be reduced to 1.212 after the optimization. More future performance predictions of the IEC water chillers are studied when the data center load rate increases and when the local weather changes in a year to discuss the year-round availability. For further study, the performance of IEC water chillers in different climate regions is also forecasted. The results indicate that it’s an effective way for IEC to achieve free cooling in regions where natural cold resources are abundant. In this study, the field test performance and prediction of IEC water chillers are provided as a typical and practical application as the natural cooling source in data centers in hot and dry areas.

Tetramethylpyrazine Attenuates Cerebral Ischemia-Reperfusion Injury by Inhibiting Ferroptosis via the AMPK / Nrf2 Pathways.

Ferroptosis is involved in the development and exacerbation of cerebral ischemia-reperfusion injury (CIRI), and its inhibition can alleviate CIRI. Tetramethylpyrazine (TMP) is used for the treatment of ischemic stroke. However, the mechanism by which TMP regulates ferroptosis in CIRI is yet to be explored. This study demonstrated the effects of TMP on ferroptosis and CIRI, including the roles of the adenosine 5'-monophosphate-activated protein kinase (AMPK)/nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway. A Sprague-Dawley rat middle cerebral artery occlusion/reperfusion (MCAO/R) model was generated. The extent of neuronal injury was measured using 2,3,5-triphenyl tetrazolium chloride staining and Garcia neurological scoring and behavior was evaluated using open-field tests. Ferroptosis-related indexes were examined and ferroptosis-related proteins were detected using western blotting. The binding modes of TMP and AMPK were evaluated using molecular docking and molecular dynamics simulations. MCAO/R rats showed a reduced cerebral infarct area and improved neurological function after TMP intervention. TMP reduced levels of Fe2+, 4-hydroxynonenal, malonaldehyde, and acyl-coenzyme synthetase long-chain family member 4 and increased levels of glutathione and glutathione peroxidase 4. Increased AMPK phosphorylation and Nrf2 expression were also detected. TMP bound tightly to the AMPKα subunit in silico, and the LEU157, VAL41, LEU33, VAL107, and TYR106 residues were important for binding. Our results indicate that TMP can alleviate CIRI by inhibiting ferroptosis via the activation of the AMPK/Nrf2 pathway, providing a theoretical basis for the clinical use of TMP in treating CIRI.

Hippocampal microRNA-181a overexpression participates in anxiety and ethanol related behaviors via regulating the expression of SIRT-1.

Understanding the molecular mechanisms underlying anxiety and ethanol-related behaviors is crucial for developing effective therapeutic interventions. This study identifies a novel role for microRNA miR-181a and its target, Sirtuin 1 (SIRT-1), in the hippocampus as contributors to anxiety-like behavior and voluntary ethanol intake. Using male and female C57BL/6 mice, we explored the causal relationship between hippocampal miR-181a expression and these behaviors. Lentivirus vectors were delivered into the hippocampus for focal miR-181a overexpression in mice. Then behaviors were observed by elevated plus maze (EPM) and open field (OF) tests. Results showed that the viral approach employed to overexpress miR-181a, in the hippocampus, resulted in increased anxiety-like behavior in the EPM and OF tests. Additionally, miR-181a overexpression exacerbated voluntary ethanol intake and preference in the two-bottle choice paradigm without affecting saccharin or quinine consumption. Mechanistically, miR-181a gain-of-function reduced SIRT-1 expression in the hippocampus. These findings demonstrate that miR-181a upregulation in the hippocampus promotes anxiety and ethanol-related behaviors, likely through SIRT-1 repression. This work highlights miR-181a as a key molecular mediator in the epigenetic regulation of mood disorders and ethanol consumption.

Field test and long-term heat extraction performance evaluation of the deep U-type borehole heat exchanger system

Field test and long-term heat extraction performance evaluation of the deep U-type borehole heat exchanger system

Xinnaoxin capsule alleviates neuropathological changes and cognitive deficits in Alzheimer's disease mouse model induced by D-galactose and aluminum chloride via reducing neuroinflammation and protecting synaptic proteins.

Originally formulated to mitigate high-altitude sickness, Xinnaoxin capsules (XNX) are composed of three traditional Chinese medicines (Rhodiola rosea L., Lycium barbarum L. and Hippophae rhamnoides) with properties of anti-hypoxia, anti-fatigue, and anti-aging. Emerging evidence now suggests that XNX may also offer therapeutic benefits in Alzheimer's disease (AD), highlighting its potential significance in the development of novel AD treatments. This study aims to investigate whether XNX improves AD-related behavioral and cognitive deficits by enhancing antioxidant defenses, reducing peripheral and neuroinflammation, and protecting neurons. The AD mouse model was established using D-galactose and aluminum chloride. Spatial memory and anxiety-like behaviors were assessed via the Morris water maze and open field tests to evaluate the therapeutic effects of XNX. Biochemical markers in hippocampal tissue and serum were measured using ELISA kits, while serum chemical composition was analyzed by LC-MS. Histopathological changes and amyloid-β deposition in the hippocampus were examined through hematoxylin-eosin (HE) staining and immunofluorescence. Additionally, hippocampal expression of apoptotic proteins Bax and Caspase-3, anti-apoptotic protein Bcl-2, and synaptic proteins PSD-95 and Syn were assessed via Western blot. Behavioral tests demonstrated that XNX significantly improved spatial learning and memory abilities, as well as reduced anxiety-like behaviors in AD mice. XNX also modulated inflammatory cytokines and oxidative stress markers in hippocampal tissue and serum, while reducing amyloid-β deposition. Further LC-MS analysis of serum revealed a marked upregulation of compounds such as adenosine following treatment, with key metabolic pathways affected, including linoleic acid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. HE staining and immunofluorescence indicated that XNX ameliorated neuronal damage and decreased amyloid-β accumulation. Western blot analysis confirmed that XNX inhibited neuronal apoptosis and preserved synaptic proteins in the hippocampus. XNX mitigates AD-induced behavioral and cognitive deficits by enhancing antioxidant defenses, reducing peripheral and neuroinflammation, and protecting neurons. Our findings provide valuable data and a theoretical foundation for the potential therapeutic application of XNX in AD treatment and its further development.

GW117 induces anxiolytic effects by improving hippocampal functions

GW117 functions as both an MT1/MT2 receptor agonist and a 5-HT2C receptor antagonist. This study aimed to investigate the anxiolytic effects of GW117 through behavioral assessments, including the open field test and novelty-suppressed feeding test (NSFT) within a chronic unpredictable mild stress (CUMS) model. GW117 was administered via oral gavage for 21 days to evaluate its sustained anxiolytic effects, with behavioral tests including the NSFT, the Vogel-conflict test, and the O-maze test. To explore the underlying mechanisms, we performed Western blot analyses to assess the expression levels of BCL2-Associated X (Bax), cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP). Additionally, BrdU labeling and immunofluorescence staining were used to examine changes in neuronal regeneration and astrocytogenesis. Our results demonstrated that GW117 produced significant anxiolytic effects across all behavioral assays, both in the CUMS model and during long-term administration. Mechanistic studies revealed that GW117 notably increased the expression of BDNF, GFAP, and Bcl-2, while reducing Bax and cleaved caspase-3 levels in the hippocampus of CUMS model rats. Furthermore, the populations of BrdU-positive and GFAP-positive cells were elevated. These findings suggest that GW117 exerts anxiolytic effects, potentially through enhancements in hippocampal function.