Feeding Tests Research Articles

Coronaridine congeners induce sedative and anxiolytic-like activity in naïve and stressed/anxious mice by allosteric mechanisms involving increased GABAA receptor affinity for GABA

The sedative and anxiolytic-like activity of two coronaridine congeners, (+)-catharanthine and (−)-18-methoxycoronaridine (18-MC), was studied in male and female mice. The underlying molecular mechanism was subsequently determined by fluorescence imaging and radioligand binding experiments. The loss of righting reflex and locomotor activity results showed that both (+)-catharanthine and (−)-18-MC induce sedative effects at doses of 63 and 72 mg/kg in a sex-independent manner. At a lower dose (40 mg/kg), only (−)-18-MC induced anxiolytic-like activity in naïve mice (elevated O-maze test), whereas both congeners were effective in mice under stressful/anxiogenic conditions (light/dark transition test) and in stressed/anxious mice (novelty-suppressed feeding test), where the latter effect lasted for 24 h. Coronaridine congeners did not block pentylenetetrazole-induced anxiogenic-like activity in mice. Considering that pentylenetetrazole inhibits GABAA receptors, this result supports a role for this receptor in the activity mediated by coronaridine congeners. Functional and radioligand binding results showed that coronaridine congeners interact with a site different from that for benzodiazepines, increasing GABAA receptor affinity for GABA. Our study showed that coronaridine congeners induce sedative and anxiolytic-like activity in naïve and stressed/anxious mice in a sex-independent fashion, likely by a benzodiazepine-independent allosteric mechanism that increases GABAA receptor affinity for GABA.

Understanding the host finding behavior of a biological weed control candidate specialist as a contribution to pre‐release risk assessments

AbstractPre‐release host range assessments of weed biocontrol agent (BCA) candidates typically rely on no‐choice and choice feeding, oviposition, and development tests. However, these tests may exclude potentially environmentally safe BCA candidates from consideration if they develop on nontarget plant species in no‐choice tests that they would not colonize in the field because of behavioral barriers during host selection. Here, we examined the behavioral responses of Ceutorhynchus rusticus Gyllenhal (Coleoptera: Curculionidae) to olfactory and visual plant cues of nine native North American and two Eurasian confamilial plant species of invasive Eurasian mustard dyer's woad, Isatis tinctoria L. (Brassicaceae). In behavioral bioassays with olfactory, visual, and combined plant cues of one plant species vs. purified air and/or empty arms (control treatments), weevils responded with attraction to all offered I. tinctoria plant cues but showed no preference for most nontarget plant species relative to control treatments. The weevil also responded faster in these bioassays to I. tinctoria cues when compared to most nontarget species. In bioassays with olfactory, visual, or combined cues of nontarget species vs. those of I. tinctoria, C. rusticus preferred I. tinctoria over most nontarget plant species (olfactory cues: eight of 11, visual cues: two of 11, and combined cues: 11 out of 11 nontarget plant species). The results also suggest that C. rusticus mainly uses olfactory or combined olfactory and visual plant cues rather than visual cues alone in the early stages of host finding. Additionally, the findings suggest that during host finding, C. rusticus prefers cues of its Eurasian field host over those of nontarget species, reducing risks of post‐release nontarget attack in the field. Assessing behavioral responses to multimodal cues can advance our understanding of BCA candidates' host discrimination and facilitate the accurate interpretation of conventional no‐choice and choice feeding and development data during pre‐release environmental safety assessments.

Spontaneously hypertensive rats vs. Wistar Kyoto and Wistar rats: An assessment of anxiety, motor activity, memory performance, and seizure susceptibility

Spontaneously hypertensive rats (SHRs) are widely accepted for modeling essential hypertension and Attention deficit hyperactivity disorder (ADHD). However, data concerning central nervous system changes associated with behavioral responses of this strain and usage of Wistar Kyoto (WKY) rats as controls are confounding. The objective of the present study was to assess the impact of anxiety and motor activity on the cognitive responses of SHRs compared to Wistar and WKY rats. In addition, the role of brain-derived neurotrophic factor (BDNF) in the hippocampus on cognitive behavior and seizure susceptibility in the three strains was evaluated. In Experiment#1, SHR demonstrated impulsive responses in the novelty suppression feeding test accompanied by impaired spatial working and associative memory in the Y maze and object recognition test compared with the Wistar rat but not WKY rats. In addition, the WKY rats exhibited diminished activity compared to Wistar rats in an actimeter. In Experiment#2, the seizure susceptibility was assessed by 3-min electroencephalographic (EEG) recording after two consecutive injections of pentylenetetrazol (PTZ) (20+40 mg/kg). The WKY rats were more vulnerable to rhythmic metrazol activity (RMA) than the Wistar rats. In contrast, Wistar rats were more prone to generalized tonic-clonic seizures (GTCS) than WKY rats and SHRs. Control SHR had lower BDNF expression in the hippocampus compared to Wistar rats. However, while the BDNF levels were elevated in the Wistar and WKY rats after PTZ injection, no change in this signaling molecule was observed in the SHR in the seizure condition. The results suggest Wistar rats as a more appropriate control of SHR than WKY rats for studying memory responses mediated by BDNF in the hippocampus. The higher vulnerability to seizures in Wistar and WKY rats compared to SHR might be linked to PTZ-induced decreased expression of BDNF in the hippocampus.

Fluoxetine Can Cause Epileptogenesis and Aberrant Neurogenesis in Male Wild-Type Mice

Antidepressants in general, and fluoxetine in particular, increase adult hippocampal neurogenesis (AHN) in mice. Here we asked how the antidepressant fluoxetine affects behavior and AHN in a corticosterone model of depression. In three groups of adult male C57BL/6j mice, we administered either vehicle (VEH), corticosterone (CORT) treatment to induce a depression-like state, or corticosterone plus a standard dose of fluoxetine (CORT+FLX). Following treatment, mice performed the open field test, the novelty suppressed feeding (NSF) test, and the splash test. Neurogenesis was assessed by means of immunohistochemistry using BrdU and neuronal maturation markers. Unexpectedly, 42% of the CORT+FLX-treated mice exhibited severe weight loss, seizures, and sudden death. As expected, the CORT-treated group had altered behaviors compared to the VEH group, but the CORT+FLX mice that survived did not show any behavioral improvement compared to the CORT group. Antidepressants generally increase neurogenesis and here we also found that compared to CORT mice, CORT+FLX mice that survived had a significantly greater density of BrdU+, BrdU+DCX+, and BrdU+NeuN+ cells, suggesting increased neurogenesis. Moreover, the density of BrdU+NeuN+ cells was increased in an aberrant location, the hilus, of CORT+FLX mice, similar to previous studies describing aberrant neurogenesis following seizures. In conclusion, fluoxetine could induce considerable adverse effects in wild-type mice, including seizure-like activity. Fluoxetine-induced neurogenesis increases could be related to this activity; therefore, proneurogenic effects of fluoxetine and other antidepressants, especially in the absence of any behavioral therapeutic effects, should be interpreted with caution.

Essential role of microglia in the fast antidepressant action of ketamine and hypidone hydrochloride (YL-0919).

Introduction: Intracerebral microglia play a vital role in mediating central immune response, neuronal repair and synaptic pruning, but its precise role and mechanism in fast action of antidepressants have remained unknown. In this study, we identified that the microglia contributed to the rapid action of antidepressants ketamine and YL-0919. Methods: The depletion of microglia was achieved with the diet containing the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 in mice. The tail suspension test (TST), forced swimming test (FST) and novelty suppressed feeding test (NSFT) were employed to evaluate the rapid acting antidepressant behavior of ketamine and YL-0919 in the microglia depletion model. The number of microglia in the prefrontal cortex (PFC) was assayed by the immunofluorescence staining. The expressions of synaptic proteins (synapsin-1, PSD-95, GluA1) and brain-derived neurotrophic factor (BDNF) in the PFC were tested by Western blot. Results: The immobility duration in FST and the latency to feed in NSFT were shortened 24h after an intraperitoneal (i.p.) injection of ketamine (10mg/kg). The microglial depletion of PLX3397 blocked the rapid antidepressant-like effect of ketamine in mice. In addition, the immobility time in TST and FST as well as latency to feed in NSFT were reduced 24h after the intragastric (i.g.) administration of YL-0919 (2.5mg/kg), and the rapid antidepressant effect of YL-0919 was also blocked by the microglial depletion using PLX5622. About 92% of microglia in the prefrontal cortex was depleted in PLX5622 diet-fed mice, while both ketamine and YL-0919 promoted proliferation on the remaining microglia. YL-0919 significantly increased the protein expressions of synapsin-1, PSD-95, GluA1 and BDNF in the PFC, all of which could be blocked by PLX5622. Conclusion: These results suggested the microglia underlying the rapid antidepressant-like effect of ketamine and YL-0919, and microglia would likely constitute in the rapid enhancing impact of synaptic plasticity in the prefrontal cortex by YL-0919.

Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat.

The pharmacological profile of cannabigerol (CBG), which acid form constitutes the main precursor of the most abundant cannabinoids, has been scarcely studied. It has been reported to target α2-adrenoceptor and 5-HT1A receptor. The locus coeruleus (LC) and the dorsal raphe nucleus (DRN) are the main serotonergic (5-HT) and noradrenergic (NA) areas in the rat brain, respectively. We aimed to study the effect of CBG on the firing rate of LC NA cells and DRN 5-HT cells and on α2-adrenergic and 5-HT1A autoreceptors by electrophysiological techniques in male Sprague-Dawley rat brain slices. The effect of CBG on the novelty-suppressed feeding test (NSFT) and the elevated plus maze test (EPMT) and the involvement of the 5-HT1A receptor was also studied. CBG (30μM, 10min) slightly changed the firing rate of NA cells but failed to alter the inhibitory effect of NA (1-100µM). However, in the presence of CBG the inhibitory effect of the selective α2-adrenoceptor agonist UK14304 (10nM) was decreased. Perfusion with CBG (30μM, 10min) did not change the firing rate of DRN 5-HT cells or the inhibitory effect of 5-HT (100μM, 1min) but it reduced the inhibitory effect of ipsapirone (100nM). CBG failed to reverse ipsapirone-induced inhibition whereas perfusion with the 5-HT1A receptor antagonist WAY100635 (30nM) completely restored the firing rate of DRN 5-HT cells. In the EPMT, CBG (10mg/kg, i.p.) significantly increased the percentage of time the rats spent on the open arms and the number of head-dipping but it reduced the anxiety index. In the NSFT, CBG decreased the time latency to eat in the novel environment but it did not alter home-cage consumption. The effect of CBG on the reduction of latency to feed was prevented by pretreatment with WAY100635 (1mg/kg, i.p.). In conclusion, CBG hinders the inhibitory effect produced by selective α2-adrenoceptor and 5-HT1A receptor agonists on the firing rate of NA-LC and 5-HT-DRN neurons by a yet unknown indirect mechanism in rat brain slices and produces anxiolytic-like effects through 5-HT1A receptor.

Inulin-type oligosaccharides of Morinda officinalis exerted antidepressant effects by reducing hippocampal inflammation.

Neuroinflammation contributes to the pathogenesis of depression. Inulin-type oligosaccharides of Morinda officinalis (IOMO) exert antidepressant-like effects in rodents and patients with depression, while the underlying mechanisms remain unclear. This study used chronic restraint stress (CRS) and lipopolysaccharide (LPS) to induce depression-like behaviors in mice. Western blotting and ELISA analysis were used to investigate the effects of IOMO on inflammatory cytokine levels. Immunofluorescence analysis was used to investigate the effects of IOMO on hippocampal NLRP3 inflammasome and microglial cells. The results suggested that 6 weeks of CRS induced significant depression-like behaviors based on the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST), which were accompanied by increases in the expression of IL-6 and the activation of hippocampal microglial cells. Chronic treatment with IOMO (25mg/kg, i.g.) for 28 days significantly reversed these depression-like behaviors and inhibited the activation of microglial cells. Furthermore, LPS (0.5mg/kg, i.p.) also significantly induced depression-like behaviors in the TST, FST, and novelty-suppressed feeding test (NSFT), as well as increased the expression of IL-1β and caspase-1, and activated the microglial cells and the NLRP3 inflammasome in the hippocampus. Treatment with IOMO for 9 days significantly reversed these depression-like behaviors and normalized the LPS-induced activation of the microglial cells and NLRP3 inflammasome. Taken together, these results suggested that IOMO exerted antidepressant-like effects via hippocampal microglial NLRP3 inflammasome mediation followed by caspase-1 inhibition and the production of IL-1β. These findings provide a basis for developing new antidepressants targeting the microglial NLRP3 inflammasome.

Acute Anti-Hyperglycaemic Activity of Five Traditional Medicinal Plants in High Fat Diet Induced Obese Rats.

Diabetes mellitus (DM), a prevalent non-communicable disease, is a metabolic condition involving defective pancreatic β-cells and/or insulin resistance. Researchers are presently exploring traditional medicinal plants to identify alternatives for treating diabetes due to the various disadvantage of current anti-diabetic medicines. The present study evaluated the anti-hyperglycaemic effects of ethanol extracts of five medicinal plants (EEMPs) (Gynura nepalensis, Glochidion thomsonii, Clerodendrum splendens, Clerodendrum infortunatum and Xanthium strumarium) which are traditionally used as an ethnomedicine to treat diabetes and numerous other health problems. High-fat fed (HFF) obese rats were used to perform acute in vivo tests, including oral glucose tolerance, feeding test, metabolic studies, and gastrointestinal motility using BaSO4 milk solution. Priliminary phytochemical screening were performed to discover the presence or absence of alkaloids, tannins, saponins, steroids, glycosides, flavonoids, and reducing sugars in extracts. Oral administration of ethanol extracts (250 mg/kg, body weight), along with glucose (18 mmoL/kg body weight), ameliorated glucose tolerance (p < 0.05-0.01). In addition, the extracts improved gut motility (250 mg/kg; p < 0.05-0.001), as well as reduced food intake during the feeding test (250 mg/kg; p < 0.05-0.001). Phytochemical screening of these medicinal plants depicted the presence of flavonoids, alkaloids, tannins, saponins, steroids and reducing sugars. Phytochemicals such as flavonoids, tannins and saponins may be responsible for the glucose-lowering properties for these plants. Additional research is warranted to fully identify the bioactive phytomolecules and mechanistic pathways that might lead to the development of a viable, cost-effective type 2 diabetes therapy.

Short-term toxicity assessment of combined use of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in vitro and in vivo.

A combination of zidovudine (AZT), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother-to-child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity. An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus, and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28-day feeding test was conducted to assess the potential subacute toxicity. In mice, the LD50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose-dependent manner in mice (P<0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high-dose group was lower than that in the control group (P<0.05); the relative weights of the liver, kidney, spleen, and brain increased (P<0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high-dose group. The hemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high-dose group increased (P<0.05). The total protein, albumin, cholesterol, and blood glucose levels of male and female rats in the high-dose group were significantly decreased (P<0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium- and high-dose groups increased significantly (P<0.05). The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions.

Evaluasi Penerapan Pengawasan Mutu Jagung Sebagai Bahan Pakan di Indonesia

Corn is the main component in the manufacture of feed which functions as an energy source for poultry and ruminants. Requirements for the quality of corn as a feed ingredient are regulated in the Indonesian National Standard (SNI) for corn which includes moisture content, damaged seeds, mouldy seeds, foreign matter and aflatoxin. The purpose of this reserch was to evaluated and analyzed the quality of corn whether it was in accordance with SNI 2020. In this research, secondary data was used that obtained from six of feed testing laboratories and three feed mills, spread across Indonesia, including: West Java, Central Java, East Java, Banten, South Sulawesi and North Sumatera. The total sample from the feed testing laboratories were 403 samples and feed mills were 5.161 samples. One sample T-test was used to analyze the result from feed testing laboratories and feed mills compare to the 2020 SNI quality values. The result of one sample T-test showed that the result of moisture content, damage seeds, moldy seeds, and foreign matter were still not in accordance with SNI. Meanwhile, aflatoxin was already fulfilled SNI.

Biology of Patanga japonica (Orthoptera, Acrididae): Nymphal growth, host plants, reproductive activity, hatching behavior, and adult morphology

The biology of Patanga japonica (Bolívar, 1898), including seasonal nymphal growth, host plants, mating, oviposition, hatching, and adult morphology, was studied under outdoor and indoor conditions in central Japan. A field census showed that this grasshopper had a univoltine life cycle and overwintered in the adult stage. Body size was found to increase with a delay in the time of adult emergence in females but not in males, and protandry was observed. The insects were mainly associated with a few plant species. Feeding tests showed that at least one of the 5 test nymphs molted to the second stadium on 37 plant species, and more than 50% did so on 23 plant species. Mating was frequently observed in April and May under outdoor conditions, and the daily maximum number of copulating pairs was positively correlated with air temperature. Copulatory behavior, including stridulation, is described in detail. Oviposition was frequently observed in May and June under outdoor conditions. Larger females produced more eggs per pod, and a negative relationship was observed between egg lengths and the number of eggs per pod, showing a trade-off. On average, female adults had 124 ovarioles. Egg hatching occurred at different times during the daytime, but the eggs from each pod hatched synchronously. Synchronous hatching was also observed in eggs kept in groups of 2, 4, and 10, but hatching occurred earlier in larger group sizes. Eggs achieved synchronous hatching by either delaying or advancing hatching time. Two eggs separated by several millimeters hatched less synchronously than those kept in contact with one another. However, similarly separated eggs restored hatching synchrony when connected by thin wire, suggesting the involvement of vibrational signals in embryo–embryo communication. Morphometric analysis suggested that P. japonica adults change some morphometric ratios in response to crowding. Variation in pronotum shape was not significantly affected by crowding.

Management of pyloric stenosis in children

A prospective study of 24 cases of infantile hypertrophic pyloric stenosis in Salahaldeen government from February 2008-february 2011. All patients evaluated according to family history, sex, age, age at starting of vomiting and hydration state. Examination done for any palpable mass and sign of dehydration, and muscle wasting ,feeding test done for all patients. Patients admitted to hospital and investigations done which includes complete blood picture, blood urea, serum electrolyte. All patients send for ultrasound study of the pyloric canal to evaluate the length and thickening of the pyloric canal and consider as appositive study if the length more than 14mm and thickening more than 4mm pyloromyotomy done for all case with very good result and most of patient discharge after 24h of surgery.

LPM570065 ameliorates anxiety-like and depressive-like behaviors in CUMS rats through regulating DNA methylation in hippocampus

Objective: In this study, we aimed to analyze the effects and underlying mechanisms of LPM570065 on behavioral phenotypes in rats with generalized anxiety disorder (GAD).Methods: The chronic unpredictable mild stress (CUMS) rats were used to observe the results of LPM570065. Total 72 male Sprague Dawley rats were divided into control, vehicle (0.5% CMC-Na), LPM570065 (32 mg/kg) and diazepam (3 mg/kg) groups, 12 rats in each group. Anxiety-like behaviors of rats were observed by elevated zero maze test and novelty-suppressed feeding test. Depressive-like behaviors of rats were detected by forced swimming test. DNA methylation in hippocampi of rats were measured by reduced representation bisulfite sequencing (RRBS). In hippocampi of rats, expressions of DNA methyltransferase (DNMT) 1 and DNMT3a proteins were measured by western blot, and density of dendritic spines was observed by Golgi staining.Results: Compared with the control group, the weights of rats were obviously decreased (p &lt; 0.001) and the rats showed anxiety-like and depressive-like behaviors (p &lt; 0.001) in the vehicle group. Compared with the vehicle group, the weights of rats were significantly increased (p &lt; 0.001) and the anxiety-like and depressive-like behaviors were improved (p &lt; 0.001) in the LPM570065 group. The results of RRBS showed that there were 49964 promoters showed hypermethylation in the LPM570065 treatment rats contrasted to the vehicle treatment rats. In addition, these promoters were enriched in signal transduction and immune function. Furthermore, the expressions of DNMT1 and DNMT3a were significantly decreased, the density of dendritic spines was significantly increased in hippocampi of LPM570065 treatment rats compared with the vehicle treatment rats.Conclusions: LPM570065 ameliorates anxiety-like and depressive-like behaviors in CUMS rats, and its mechanism is possible associated with downregulating DNA methylation in hippocampus.

Real Time Cloud based Fault Detection and Alert for Antenna Array Using CNN

The rise of smart antennas made it imperative to use adaptive beam forming, but single-element failure in array antenna disturbs the radiation pattern. Hence, to achieve adaptive beam forming, detecting and locating faults in an antenna array is a must for correction in the radiation pattern. The presented work in this paper provides real-time monitoring and alert for fault occurrence in antenna arrays. Fault detection is performed by an optimized Convolutional Neural Network (CNN), and the Thingspeak web service is utilized to store fault detection information on the cloud to get the visualization of faults. Voice over Internet Protocol (VoIP) Application programming interface (API) provides an alert in real-time once the fault is detected. The filter kernel parameters, number of convolutional layers, and dense layers of the fully connected neural network are tuned to minimize the mean square error (MSE). 16 element (4 × 4) planar microstrip array antenna is simulated on Ansys HFSS, and by introducing discontinuity, i.e. one type of defect in the corporate feed network, a training and testing set of 374 samples considering single element fault are used to train the CNN Model with a 0.3 validation split. Further performance of the same model by changing the last layer of a fully connected layer is evaluated to check the effectiveness of model when two elements are faulty.

Electroacupuncture treatment ameliorates depressive-like behavior and cognitive dysfunction via CB1R dependent mitochondria biogenesis after experimental global cerebral ischemic stroke.

This study aimed to identify the effect of electroacupuncture (EA) treatment on post-stroke depression (PSD) and explore whether cannabinoid receptor 1 (CB1R)-mediated mitochondrial biogenesis accounts for the treatment effect of EA. The PSD mouse model was induced by a consecutive 14-day chronic unpredictable stress operation after 7 days of recovery from the bilateral common carotid artery occlusion surgery. Either EA treatment or sham stimulation was performed for 14 consecutive days from Day 7 after the BCCAO operation. Subjects' PSD-like behaviors were tested via open field test, sucrose preference test, novelty suppressed feeding test, tail suspension test, and forced swim test, and subjects' cognitive function was examined using Y-maze and novelty object recognition test. In addition, the levels of CB1R, mitochondrial biogenesis-related proteins (nuclear transcription factor 1, NRF1; mitochondrial transcription factor A, TFAM), proteins related to mitochondrial function (Cytochrome C, Cyto C; AIF, COX IV), and mitochondrial DNA were measured. To elucidate the role of CB1R in EA treatment, CB1R antagonists AM251 and CB1R-shRNA were given to mice before EA treatment. Likewise, subjects' depressive-like behaviors, cognitive function, mitochondrial function, and mitochondrial biogenesis were examined after the PSD procedure. It has been showed that EA successfully ameliorated depressive-like behaviors, improved cognitive dysfunctions, and upregulated CB1R, NRF1 and TFAM expressions. However, the supplementation of AM251 and CB1R-shRNA blocked the antidepressant-like effects generated by EA, and EA failed to improve cognitive dysfunction, upregulate CB1R protein expression, and increase mitochondrial function and biogenesis. Altogether, these results indicated that EA ameliorated PSD-like behaviors in mice, improved cognitive dysfunctions after PSD, and promoted mitochondrial biogenesis by activating CB1R, a novel mechanism underlying EA's antidepressant-like effects in treating PSD.

The Brown Alga Padina australis Total Extract and Depressive-like Behavior Following BCG Inoculation in Mice

Background: Depression is an important psychological disorder because it is a common mental illness that leads to morbidity and suicide. Although appropriate antidepressant drugs exist, they usually have unpleasant side effects and delayed onset. Objectives: Introducing new compounds such as medicinal plants and oceanic living organisms such as alga is appropriate. Here the depressive-like effects of Padina australis Hauck total extract (PAE) were evaluated following depression induced by Bacillus Calmette–Guérin (BCG) in mice. Methods: Male NMRI mice (average weight: 27±2 g) were used. A single BCG 0.2 mL/mouse was inoculated. PAE effective dose (40 mg/kg) and imipramine (10 mg/kg) were administered as the reference drug for 14 days. The control animals received normal saline. All treatments were administered intraperitoneally. After evaluating the locomotor activity, different depression criteria were assessed by forced swimming test (FST), sucrose preference (SP) test, and novelty-suppressed feeding test (NSFT). Results: Depression was induced by BCG. The selected PAE dose did not cause a significant change in the locomotor activity compared with the control (139±16.9 count), while the immobility time in FST reduced (45.1±11.4 s vs BCG, P&lt;0.001). During the NSFT, the latency decreased (94.7±18.5 s vs BCG, P=0.0365), food intake increased (17.4±2.11 mg/g body weight vs BCG, P=0.023), and SP up to 79.3±4.7%. These changes were similar to imipramine. Conclusion: PAE showed antidepressant-like effects as despair behavior reduced during FST. Based on NSFT, the stress declined, and animal appetite increased, while SP revealed remission of anhedonia. Further studies are suggested regarding the antidepressant effects of PAE different partitions.

Evaluating the Impact of Commonly Used Pesticides on Honeybees (Apis mellifera) in North Gonder of Amhara Region, Ethiopia.

Global honeybee losses and colony decline are becoming continuous threat to the apicultural industry, as well as, for food security and environmental stability. Although the putative causes are still unclear, extensive exposure of bees to pesticides could be the possible factor for worldwide colony losses. This study was aimed at evaluating the impact of nine commonly used pesticide incidents on adult worker honeybees (A. mellifera) under the laboratory condition, in North Gonder of Amhara region, Ethiopia. Feeding test, contact test, and fumigation tests were carried out for each pesticide following the standard procedures, and each pesticide toxicity was compared to the standard toxic chemical, dimethoate 40% EC (positive control), and to 50% honey solution (negative control). The results revealed that all the tested pesticides caused significant deaths of the experimental bees (P < 0.05) in all the tests when compared to the negative control. Diazinon 60% EC, endosulfan 35% EC, and malathion 50% EC were appeared highly toxic causing 100% mortality of bees, while chlorsulfuron 75% WG killed 90% of the experimental bees as tested via feeding. On the other hand, agro-2, 4-D and its mixture with glycel 41% EC are moderately toxic, and mancozeb 80% WP and glycel 41% EC were slightly toxic to honeybees as compared to the positive control (dimethoate 40% EC). Suddenly, diazinon 60% EC and malathion 50% EC triggered 100% mortality of bees, while endosulfan 35% EC and chlorsulfuron 75% WG caused 63.63% and 90.82% of bee mortality, respectively, when evaluated via contact test. The fumigation test also showed that chlorsulfuron 75% WG, diazinon 60% EC, and endosulfan 35% EC caused 100%, 86.7%, and 65.6% mortality rate of bees. Our result also highlighted that tested LD50 of all pesticide incidents were significantly lower than the manufacturer-based LD50. This shows that local honeybees A. m. jemenetica are extremely sensitive to commonly used agricultural pesticides, which may affect the colony level due to the intensive application of these pesticides in Ethiopia.

Polygonum sibiricum polysaccharides exert the antidepressant-like effects in chronic unpredictable mild stress-induced depressive mice by modulating microbiota-gut-brain axis.

Polygonum sibiricum polysaccharides (PSP) are one of the main active components of Polygonatum sibiricum, which is a traditional Chinese medicine with food and drug homologies. Recent studies have revealed the antidepressant-like effects of PSP. However, the precise mechanisms have not been clarified. Therefore, the present study was conducted to explore that whether PSP could exert the antidepressant-like effects via microbiota-gut-brain (MGB) axis in chronic unpredictable mild stress (CUMS)-induced depressive mice by transplantation of fecal microbiota (FMT) from PSP administration mice. FMT markedly reversed the depressive-like behaviors of CUMS-induced mice in the open field, the sucrose preference, the tail suspension, the forced swimming, and the novelty-suppressed feeding tests. FMT significantly increased the levels of 5-hydroxytryptamine and norepinephrine, decreased the levels of the pro-inflammatory cytokines in the hippocampus and reduced the levels of corticosterone, an adrenocorticotropic-hormone, in the serum of CUMS-induced mice. In addition, administration of PSP and FMT significantly increased the expressions of ZO-1 and occludin in the colon and decreased the levels of lipopolysaccharide and interferon-γ in the serum of CUMS-induced mice. Moreover, administration of PSP and FMT regulated the signaling pathways of PI3K/AKT/TLR4/NF-κB and ERK/CREB/BDNF. Taken together, these findings indicated that PSP exerted antidepressant-like effects via the MGB axis.

Alpinia oxyphylla Miq. volatile oil ameliorates depressive behaviors and inhibits neuroinflammation in CUMS-exposed mice by inhibiting the TLR4-medicated MyD88/NF-κB signaling pathway

This study aimed to explore the antidepressant effect and underlying mechanism of the Alpinia oxyphylla Miq. volatile oil (AOVO) in mice exposed to chronic unpredictable mild stress (CUMS). C57BL/6 mice were grouped and administered with different dosages of AOVO (0.25, 0.50, 1.00, or 2.00 mL/kg body weight, i.g.), TAK242 (a TLR4 inhibitor, 0.75 mg/kg body weight, i.p.), or TAK242 (0.75 mg/kg body weight, i.p.) + AOVO (0.50 mL/kg body weight, i.g.) for 21 days. Depression-like symptoms in the mice were then evaluated through their body weight gain (BW), the open field test (OFT), the sucrose preference test (SPT), the novelty-suppressed feeding test (NSFT), and forced swimming test (FST). The concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and 5-hydroxytyrptamine (5-HT) in the mice were determined using ELISA kits. Hematoxylin and eosin (HE) dying were performed for histopathological examination. The expression of inflammatory proteins was assessed through western blotting (WB) and immunofluorescence staining. AOVO was found to improve the behavioral indexes of CUMS-exposed mice behavioral and synergize TAK242 to mitigate both their depressive symptoms and neuroinflammation. Moreover, AOVO was found to inhibit the hippocampal damage, decrease inflammatory cytokines (Reduced IL-1β, IL-6, and TNF-α by 19.97 %, 22.87 %, and 24.13 %, respectively), and downregulate the expression of TLR4/MyD88/NF-κB signaling pathway-related proteins in the hippocampus of CUMS-exposed mice (Reduced TLR4, MyD88, and NF-κB by 46.14 %, 42.48 %, and 38.08 %, respectively). These findings demonstrate that AOVO can ameliorate depressive behaviors and mitigate neuroinflammation in the CUMS-exposed mice via suppressing the TLR4-medicated MyD88/NF-κB signaling pathway.

Electronic Vaporization of Nicotine Salt or Freebase produces differential effects on metabolism, neuronal activity and behavior in male and female C57BL/6J mice

The use of Electronic Nicotine Delivery Systems (ENDS) is increasing in prevalence and popularity. ENDS are a rapidly evolving technology as devices and e-liquid formulations adapt to policy restrictions and market demand. To identify the impacts of nicotine formulation and concentration, we exposed female and male C57BL/6J mice to passive electronic vaporization of different nicotine formulations (freebase or salt) and concentrations (1% or 3%) and measured serum nicotine metabolite levels, brain activity by cFos expression, and anxiety-like and motivated behavior using the novelty suppressed feeding test. We found that the 3% freebase nicotine vapor group displayed significantly higher serum nicotine levels than either 1% or 3% nicotine salt formulations, and female mice displayed higher serum nicotine and cotinine levels compared to males. Central amygdala (CeA) activity was significantly elevated in male mice following nicotine vapor exposure, but the increase was not significantly different between nicotine vapor groups. CeA activity in female mice was unaffected. In contrast, increased activity in the ventral tegmental area (VTA) was only observed in female mice exposed to 3% nicotine freebase and specifically in the dopaminergic population. Anxiety-like behavior in female mice was relatively unaffected by nicotine vapor exposure, however male mice displayed increased anxiety-like behavior and reduced motivation to feed after vapor exposure, specifically in the 3% freebase group. These results identify important sex differences in the impact of nicotine formulation and concentration on nicotine metabolism, brain region-specific activity and anxiety-like behavior, which may have significant relevance for different consequences of vaping in men and women.