Measures Of Locomotor Activity Research Articles

Low-cost conditioned place preference setup including video recording and analysis of behaviour

The conditioned place preference (CPP) paradigm is widely used in rodent research to test the rewarding and aversive properties of different stimuli. Despite its relative simplicity, commercially available CPP systems are often costly. Here we describe the construction of a CPP setup and a behavioral data analysis pipeline incorporating:• a CPP box which can be built in a single day by using widely available and affordable materials.• an open source computer system for data acquisition (based on Raspberry Pi).• a freely available behavioural analysis software.The behavioural analysis allows for measurement of both locomotor activity and time spent in a zone of interest. Including all components, our setup costs ~1/10 of the cost of the least expensive commercially available CPP boxes alone (not including data acquisition and analysis). We validated the setup by showing that a 4 mg/kg dose of amphetamine increases locomotor activity acutely in adolescent male mice and induces conditioned preference for the drug-paired compartment in the CPP test.

Locomotor activity and histological changes observed in a mouse model of knee osteoarthritis.

[Purpose] This study aimed to elucidate the changes in locomotor activity in a mouse model of knee osteoarthritis (OA). [Materials and Methods] Fourteen 20-week-old mice were divided into control and OA groups. Knee OA was surgically induced under anesthesia by destabilizing the meniscus. The OA group was reared normally for 8 weeks following surgery, during which OA was induced. Locomotor activity was measured every hour for 8 weeks using an infrared locomotor activity measurement device. Histological changes were evaluated according to the classification-system of Glasson. [Results] Locomotor activity in the OA group significantly decreased up to 2 weeks after surgery. Histological findings in the control group revealed an irregular cartilage surface in a portion of the tibia with no other abnormalities. Contrastingly, those in the OA group had eburnation of the medial femoral condyle, as well as fibrillation and fissures in the medial tibial plateau. Histological scores in the OA group were significantly higher than the control group. [Conclusion] Locomotor activity evaluations, in addition to histological scores and findings, are imperative for studies aiming to clarify the disease state and effect of interventions using mice models.

Effects of Chaenomeles maulei Fruit Juice on Reserpine-induced Behavioral Changes in Rats.

The fruit juice from. The aim of the current study was to investigate the effects of. The experimental design included a total of 50 animals, divided in the following groups: control, R, R+CMFJ2.5, R+CMFJ5, and R+CMFJ10. All groups except the control received a single intraperitoneal injection of reserpine while the Control group was injected with the vehicle. CMFJ was applied through an orogastric cannula at 0, 19, and 23 hours after reserpine injection at doses of 2.5 ml/kg, 5 ml/kg, and 10 ml/kg to groups R+CMFJ2.5, R+CMFJ5, and R+CMFJ10, respectively. The groups control and R received distilled water (10 ml/kg) at the same time points. The open field test (OFT) and the forced swim test (FST) were carried out. In the OFT, crossings and rearings were recorded as a measure of locomotor activity. In the FST, the immobility time served as a measure of depressive-like behavior. In the OFT, the number of crossings of rats were significantly reduced (p<0.05) by reserpine. CMFJ antagonized the effects of reserpine on rat locomotor activity. In the FST, reserpine caused an insignificant reduction of the immobility time while CMFJ reversed this effect probably by increasing the locomotor activity. CMFJ reversed reserpine-induced hypokinesia in rats. This effect of CMFJ might be attributed to the polyphenols found in very high concentrations in the juice.

Inhibition of ADAMTS-4 Expression in Olfactory Ensheathing Cells Enhances Recovery after Transplantation within Spinal Cord Injury.

Spinal cord injury (SCI) induces permanent loss of sensitive and motor functions below the injury level. To date, a wide variety of cells has been used as biotherapies to cure SCI in different animal paradigms. Specifically, olfactory ensheathing cells (OECs) is one of the most promising. Indeed, OECs have been shown to enhance recovery in many animal studies. Moreover, OECs transplantation has been applied to a paraplegic patient and have shown beneficial effects. However, it has been reported that the significant level of recovery varies among different patients. Therefore, it is of primary importance to enhance the regenerative efficiency of OECs for better translations. Recently, it has been shown that inhibiting ADAMTS4 expression in glial cells in vitro increases their synthesis of neurotrophic factors. We hypothesized that the expression of neurotrophic factors secreted by OECs can be increased by the deletion of ADAMTS4. Taking advantage of ADAMTS4-/- mouse line, we produce ADAMTS4 deficient primary OEC cultures and then we investigated their regenerative potential after SCI. By using quantitative polymerase chain reaction, bioluminescence imaging, measurement of locomotor activity, electrophysiological studies, and immunohistochemistry, our results show that ADAMTS4-/- olfactory bulb OEC (bOECs) primary cultures upregulate their trophic factor expression in vitro, and that the transplantation of ADAMTS4-/- bOECs in a severe SCI model increases functional recovery and tissue repair in vivo. Altogether, our study reveals, for the first time, that primary bOEC cultures transplantation can be potentialized by inhibition of the expression of ADAMTS4.

Acute net stress of young adult zebrafish (Danio rerio) is not sufficient to increase anxiety-like behavior and whole-body cortisol.

In recent years, the zebrafish (Danio rerio) has become a popular model to study the mechanisms of physiological and behavioral effects of stress, due to the similarity in neural structures and biochemical pathways between zebrafish and mammals. Previous research in this vertebrate animal model has demonstrated an increase in whole-body cortisol resulting from an acute (30-second) net handling stress, but it remains unclear whether such a stressor will concomitantly increase anxiety-like behavior. In addition, as the previous study examined the effects of this acute stressor in adult zebrafish after a brief period of isolation, it is unclear whether this stressor would be effective in eliciting cortisol increases in younger aged subjects without isolation. In the current study, young adult zebrafish (approximately 90 days post-fertilization) were briefly exposed to a net handling stressor and were subsequently subjected to either the novel tank test or the light/dark preference test. The novel tank test was used to measure exploration and habituation in response to a novel environment, and the light/dark preference test was used to measure locomotor activity and scototaxis behavior. All subjects were sacrificed 15 minutes post-stressor and were analyzed for whole-body levels of cortisol. Contrary to expectations, there was no effect of acute net handling on cortisol levels. Similarly, acute net handling did not significantly induce anxiety-like behavior during the novel tank test or the light/dark preference test. Our findings demonstrate that there are possible developmental differences in response to an acute net handling stress, as we did not observe alterations in hormonal or behavioral measures of anxiety in young adult zebrafish. Alternatively, if zebrafish are not isolated before the stressor, they may be more resilient to a brief acute stressor. These results suggest the need for a different or more intense acute stressor in order further explore neuroendocrine mechanisms and anxiety-like behavior at this developmental stage in the zebrafish animal model.

Maternal ethanol consumption before paternal fertilization: Stimulation of hypocretin neurogenesis and ethanol intake in zebrafish offspring

There are numerous clinical and pre-clinical studies showing that exposure of the embryo to ethanol markedly affects neuronal development and stimulates alcohol drinking and related behaviors. In rodents and zebrafish, our studies show that embryonic exposure to low-dose ethanol, in addition to increasing voluntary ethanol intake during adolescence, increases the density of hypothalamic hypocretin (hcrt) neurons, a neuropeptide known to regulate reward-related behaviors. The question addressed here in zebrafish is whether maternal ethanol intake before conception also affects neuronal and behavioral development, phenomena suggested by clinical reports but seldom investigated. To determine if preconception maternal ethanol consumption also affects these hcrt neurons and behavior in the offspring, we first standardized a method of measuring voluntary ethanol consumption in AB strain adult and larval zebrafish given gelatin meals containing 10% or 0.1% ethanol, respectively. We found the number of bites of gelatin to be an accurate measure of intake in adults and a strong predictor of blood ethanol levels, and also to be a reliable indicator of intake in larval zebrafish. We then used this feeding paradigm and live imaging to examine the effects of preconception maternal intake of 10% ethanol-gelatin compared to plain-gelatin for 14 days on neuronal development in the offspring. Whereas ethanol consumption by adult female HuC:GFP transgenic zebrafish had no impact on the number of differentiated HuC+ neurons at 28 h post-fertilization (hpf), preconception ethanol consumption by adult female hcrt:EGFP zebrafish significantly increased the number of hcrt neurons in the offspring, an effect observed at 28 hpf and confirmed at 6 and 12 days post-fertilization (dpf). This increase in hcrt neurons was primarily present on the left side of the brain, indicating asymmetry in ethanol's actions, and it was accompanied by behavioral changes in the offspring, including a significant increase in novelty-induced locomotor activity but not thigmotaxis measured at 6 dpf and also in voluntary consumption of 0.1% ethanol-gelatin at 12 dpf. Notably, these measures of ethanol intake and locomotor activity stimulated by preconception ethanol were strongly, positively correlated with the number of hcrt neurons. These findings demonstrate that preconception maternal ethanol consumption affects the brain and behavior of the offspring, producing effects similar to those caused by embryonic ethanol exposure, and they provide further evidence that the ethanol-induced increase in hcrt neurogenesis contributes to the behavioral disturbances caused by ethanol.

Enhanced Social Dominance and Altered Neuronal Excitability in the Prefrontal Cortex of Male KCC2b Mutant Mice.

The K-Cl cotransporter KCC2 is essential in the development of the "GABA switch" that produces a change in neuronal responses to GABA signaling from excitatory to inhibitory early in brain development, and alterations in this progression have previously been hypothesized to play a causal role in autism spectrum disorder (ASD). We investigated the KCC2b (Slc12a5) heterozygous knockout mouse using a battery of rodent behavioral tests relevant to core and comorbid ASD symptoms. Compared to wild-type littermates, KCC2+/- mice were normal in standard measures of locomotor activity, grooming and digging behaviors, and social, vocalization, and anxiety-like behaviors. However, KCC2+/- mice exhibited increased social dominance behaviors and increased amplitude of spontaneous postsynaptic currents in the medial prefrontal cortex (PFC) that were previously implicated in governing social hierarchy and dominance behaviors. Treatment of wild-type mouse brain slices with the KCC2 inhibitor VU0240511 increased the amplitude and frequency of excitatory postsynaptic currents, partially recapitulating the phenotype of KCC2+/- mice. These findings indicate that the activity of KCC2 plays a role in social dominance, in parallel with effects on PFC signaling, further suggesting that KCC2 function has some relevance to social behavior but without the breadth of impact on autism-like behavior suggested by previous studies. Further testing could assess whether KCC2 alters other circuits and whether additional factors such as environmental insults may precipitate autism-related behavioral phenotypes. Autism Research 2019, 12: 732-743. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: A mouse model of altered chloride transporter expression was used to look for a role in behaviors and brain function relevant to autism. There was an imbalance in signaling in the prefrontal cortex, and increased social dominance behavior, although other autism-related behaviors were not changed. These findings indicate that altered chloride transporter function affects prefrontal cortex function and social dominance without a broader impact on autism-like behaviors.

Comparative Behavioral Studies of Rimonabant and a Peripherally Restricted CB1 Receptor Antagonist

In recent years, cannabinoid subtype 1 receptor (CB1R) antagonists have been developed to treat obesity and metabolic syndrome. Unfortunately, rimonabant (SR141716A) the first marketed drug produced CNS‐related adverse effects including depression and suicidal ideation and was withdrawn from the market. Recent data suggest that blockade of peripheral CB1R receptors can mitigate symptoms associated with metabolic syndrome independent of CNS effects. Therefore, CNS‐sparing CB1R antagonists that have limited transport across the blood‐brain‐barrier are under development. We have developed several potent, selective and drug‐like small molecule inverse agonists of CB1R with vastly reduced brain exposure (e.g. RTI‐1092915). As part of an integrated drug discovery program it was deemed prudent to evaluate lead compounds for evidence of possible neuropsychiatric side effects.First, a behavioral battery was performed in rats to assess the effects of rimonabant after acute and chronic dosing regimens. Rimonabant (vehicle, 3, 10 mg/kg) was administered i.p. 30 minutes prior to the simultaneous assessment of locomotor activity, grooming, feeding, and defecation. Rimonabant significantly decreased food consumption, decreased measures of locomotor activity, increased scratching and wet‐dog shakes, and increased defecation. Subsequently, animals were dosed daily but were always tested in a drug‐free state, as not to test the acute effects of the drug on top of the background of chronic dosing. The highest dose of rimonabant tested significantly decreased marble burying behavior, presumably anxiolysis, while there were trends for anxiogenic effects in the light‐dark box. In an attempt to clarify these results, behavioral tests including forced swim test and preference in two‐bottle choice for sucrose were performed, however there was no effect of treatment. Chronic treatment with rimonabant also significantly attenuated weight gain in these animals despite having ad libitum food.A similar battery of behaviors was performed to directly compare rimonabant (10 mg/kg) to RTI‐ 1092915 (3 mg/kg; a dose previously shown to reduce alcoholic steatosis). There were no significant effects with RTI‐1092915 while rimonabant again acutely decreased food intake, weight gain and locomotor activity. The chronic dosing of rimonabant, but not RTI‐1092915, significantly decreased time spent near an intruder animal in a social interaction paradigm.Our preliminary data suggests that certain behaviors, either after acute or chronic dosing, could be used to distinguish peripherally restricted and CNS penetrant CB1R antagonists. Specifically, social interaction could be used to assess the negative impact of chronic treatment with centrally‐acting CB1R antagonists. Finally, RTI‐1092915 shows no or mitigated negative effects in the behaviors tested. Therefore, RTI‐1092915 may be a lead candidate to treat metabolic syndrome and liver diseases through inhibition of peripheral CB1R receptors.Support or Funding InformationNIH DK100414, AA023256This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Automated Measurements of Sleep and Locomotor Activity in Mexican Cavefish

Automated Measurements of Sleep and Locomotor Activity in Mexican Cavefish

Automated Measurements of Sleep and Locomotor Activity in Mexican Cavefish.

Across phyla, sleep is characterized by highly conserved behavioral characteristics that include elevated arousal threshold, rebound following sleep deprivation, and consolidated periods of behavioral immobility. The Mexican cavefish, Astyanax mexicanus (A. mexicanus), is a model for studying trait evolution in response to environmental perturbation. A. mexicanus exist as in eyed surface-dwelling forms and multiple blind cave-dwelling populations that have robust morphological and behavioral differences. Sleep loss has occurred in multiple, independently-evolved cavefish populations. This protocol describes a methodology for quantifying sleep and locomotor activity in A. mexicanus cave and surface fish. A cost-effective video monitoring system allows for behavioral imaging of individually-housed larval or adult fish for periods of a week or longer. The system can be applied to fish aged 4 days post fertilization through adulthood. The approach can also be adapted for measuring the effects of social interactions on sleep by recording multiple fish in a single arena. Following behavioral recordings, data is analyzed using automated tracking software and sleep analysis is processed using customized scripts that quantify multiple sleep variables including duration, bout length, and bout number. This system can be applied to measure sleep, circadian behavior, and locomotor activity in almost any fish species including zebrafish and sticklebacks.

Shift Work Disrupts Circadian Regulation of the Transcriptome in Hospital Nurses.

Circadian misalignment between sleep and behavioral/feeding rhythms is thought to lead to various health impairments in shift workers. Therefore, we investigated how shift work leads to genome-wide circadian dysregulation in hospital nurses. Female nurses from the University of Alabama at Birmingham (UAB) Hospital working night shift ( n = 9; 29.6 ± 11.4 y) and day shift ( n = 8; 34.9 ± 9.4 y) participated in a 9-day study measuring locomotor activity and core body temperature (CBT) continuously. Additionally, cortisol and melatonin were assayed and peripheral blood mononuclear cells (PBMCs) were harvested for RNA extraction every 3 h on a day off from work. We saw phase desynchrony of core body temperature, peak cortisol, and dim light melatonin onset in individual night-shift subjects compared with day-shift subjects. This variability was evident even though day- and night-shift nurses had similar sleep timing and scheduled meal times on days off. Surprisingly, the phase and rhythmicity of the expression of the clock gene, PER1, in PBMCs were similar for day-shift and night-shift subjects. Genome-wide microarray analysis of PBMCs from a subset of nurses revealed distinct gene expression patterns between night-shift and day-shift subjects. Enrichment analysis showed that day-shift subjects expressed pathways involved in generic transcription and regulation of signal transduction, whereas night-shift subjects expressed pathways such as RNA polymerase I promoter opening, the matrisome, and endocytosis. In addition, there was large variability in the number of rhythmic transcripts among subjects, regardless of shift type. Interestingly, the amplitude of the CBT rhythm appeared to be more consistent with the number of cycling transcripts for each of the 6 subjects than was melatonin rhythm. In summary, we show that shift-work patterns affect circadian alignment and gene expression in PBMCs.

Cardiovascular effects of 3,4-methylenedioxypyrovalerone (MDPV) in male and female Sprague-Dawley rats

Background3,4-methylenedioxypyrovalerone (MDPV) toxicity includes intense neurological and cardiovascular events. We examined MDPV-induced cardiovascular, temperature, and locomotor effects following escalating and repeated MDPV administration in adult male and female Sprague-Dawley rats and compared these effects to cocaine in male rats. MethodsTelemetry devices were surgically implanted to allow continuous measurement of cardiovascular, temperature, and locomotor activity over a 22 h period after dosing. Rats were administered increasing intraperitoneal (IP) MDPV doses (1–5.6 mg/kg) every other day, followed two days later by a binge regimen of four injections of 3 mg/kg MDPV at 2 h intervals. MDPV serum concentrations were measured by LC–MS/MS. Cocaine (3–30 mg/kg) and four injections of 30 mg/kg IP were administered to male rats for comparison with male MDPV data. ResultsThe duration of MDPV cardiovascular effects was significantly greater (p < 0.05) in male rats than female rats at 3–5.6 mg/kg. The ED50 for MDPV-induced locomotor was significantly lower in males (2.4 ± 0.3) than females (3.4 ± 0.2). Males showed significantly greater variability in MDPV serum concentrations than females after binge dosing. MDPV produced five-fold more potent cardiovascular effects than cocaine in male rats. MDPV did not alter thermoregulation in either sex, but cocaine binge administration decreased temperature. ConclusionEffects of MDPV on temperature were not significantly different between sexes. MDPV-induced cardiovascular and locomotor effects in males lasted significantly longer and were more potent than in females. These differences appeared to be related to pharmacokinetic factors leading to greater variance in MDPV serum concentrations in males.

Continuous measurement of locomotor activity during convalescence and acclimation in group-housed rats

Locomotor activity is affected by a range of factors in addition to experimental treatment, including the breeding environment. Appropriate convalescence and acclimation are important for animal experiments, because environmental changes and physical burden can result from surgery, transportation, and cage exchange. However, the duration that locomotor activity is affected by these factors is currently unclear, because it has traditionally been difficult to measure locomotor activity in multiple group-housed animals in any location other than the analysis room. In the present study, we analyzed the locomotor activity of group-housed rats using a nano tag® after surgery, transportation, and cage exchange. The nano tag®, a new device for analyzing activity, can measure locomotor activity in laboratory animals with no limitation on the number of animals in same cage. Any type of cage can be used for analysis, at any time of day, and in any location. Nano tags® were subcutaneously implanted in male rats (F344/NSlc, 6 weeks of age) and locomotor activity was continuously measured after surgery, transportation, and cage exchange. Significant activity changes were observed in rats after transportation and cage exchange, 9 days and 3 h after the event, respectively. The results suggest that continuous measurement of locomotor activity with nano tags® can be used to monitor changes in activity induced by environmental changes, and will be helpful for designing animal experiments analyzing locomotor activity.

Negatively Skewed Locomotor Activity Is Related to Autistic Traits and Behavioral Problems in Typically Developing Children and Those With Autism Spectrum Disorders.

An important objective for researchers and clinicians is to gain a better understanding of the factors that underlie autism spectrum disorders (ASDs). It is possible that investigating objective and quantitative behavioral phenotypes and their relationship to clinical characteristics, such as autistic traits and other emotional/behavioral problems, might facilitate this process. Given this, in the current study we examined the link between locomotor dynamics and clinical characteristics, including autistic traits and emotional/behavioral problems, in children with ASD (n = 14) and typically developing (TD) children (n = 13). A watch-type actigraph was used to continuously measure locomotor activity which was assessed in terms of mean activity levels and the skewness of activity. Parents assessed quantitative autistic traits using the Japanese version of the Social Responsiveness Scale (SRS) and emotional and behavioral problems using the Japanese version of the Strengths and Difficulties Questionnaire (SDQ). Results showed that among all children, all-day activity was more negatively skewed, suggesting sporadic large all-day “troughs” in activity and was significantly correlated with the SRS social awareness subscale score (ρ = −0.446, p = 0.038). In addition, the more negatively skewed daytime locomotor activity was associated with the SDQ Hyperactivity Inattention subscale score (ρ = −0.493, p = 0.020). The results of this study indicate that investigating locomotor dynamics may provide one way to increase understanding of the neurophysiological mechanisms underlying the clinical characteristics of ASD.

The Open Field Test for Measuring Locomotor Activity and Anxiety-Like Behavior.

The open field test is used in studies of the neurobiological basis of anxiety and screening for novel drug targets and anxiolytic compounds. This test uses a camera to measure movement of the test animal in the peripheral and central zones of a 42×42×42cm polyvinyl chloride box. This chapter describes a protocol for carrying out the open-field test for assessment of locomotion and anxiety-like behavior in mice.

Analyzing Spatial Learning and Prosocial Behavior in Mice Using the Barnes Maze and Damsel-in-Distress Paradigms.

The Barnes maze is a reliable measure of spatial learning and memory that does not require food restriction or exposure to extremely stressful stimuli. The Barnes maze can also assess other mouse behaviors, such as general motivation to escape from the maze platform and exploratory behavior. The Barnes maze can measure whether a genetic mutation or environmental variable can impact the acquisition and retention of spatial memories, as well as provide information about the search strategy employed by the mice. Here we use the Barnes maze to detect a memory deficit in adult mice following a single developmental ethanol exposure event. The newly described Damsel-in-Distress paradigm exposes a male mouse to a female mouse trapped in a chamber in the open center field of the arena. It provides an opportunity for the mouse to socially respond to the trapped female and exhibit prosocial behavior. The Damsel-in-Distress paradigm can also be used to examine mouse behavior in a novel arena and measure locomotor activity. Both the Barnes Maze and the Damsel-in-Distress protocols require minimal financial investment and most aspects of the tests can be constructed from common lab supplies. These flexible and accessible tools can also be used to detect behavioral changes over the course of development.

JM-20, a novel hybrid molecule, protects against rotenone-induced neurotoxicity in experimental model of Parkinson’s disease

Oxidative stress and mitochondrial dysfunction are two pathophysiological factors often associated with the neurodegenerative process involved in Parkinson’s disease (PD). The aim of this study was to investigate the effects of a novel hybrid molecule, named JM-20, in different in vitro and in vivo models of PD induced by rotenone. To perform in vitro studies, SHSY-5Y cells were exposed to rotenone and/or treated with JM-20. To perform in vivo studies male Wistar rats were intoxicated with rotenone (2.5 mg/kg) via intraperitoneal injection and/or treated with JM-20 (40 mg/kg) administered via oral (for 25 days, both treatment). Rats were evaluated for global motor activity by measurement of locomotor activity. In addition, the effects on mortality, general behavior and redox parameters were also investigated. JM-20 protected SHSY-5Y cells against rotenone-induced cytotoxicity, evidenced by a significant diminution of cell death. In in vivo studies, JM-20 prevented rotenone-induced vertical exploration and locomotion frequency reductions, moreover prevented body weight loss and mortality induced by rotenone. It also improved the redox state of rotenone-exposured animals by increasing superoxide dismutase and catalase activities, total tissue-SH levels and decreasing malondialdehyde concentrations. Finally, JM-20 inhibited spontaneous mitochondrial swelling and membrane potential dissipation in isolated rats brain mitochondria. These results demonstrate that JM-20 is a potential neuroprotective agent against rotenone-induced damage in both in vitro and in vivo models, resulting in reduced neuronal oxidative injury and protection of mitochondria from impairment.

PO-264 Target Mitochondria Metabolism and Energy Expenditure in Muscle Atrophy, Sarcopenia and Cachexia

Objective Muscle atrophy is a common and clinically important outcome of many diseases and hospitalization bed rest. Mechanical unloading of skeletal muscles may result in a rapid loss of muscle mass and mitochondria dysfunction. And the recovery from disuse muscle atrophy is usually complete in young healthy adults but is delayed and often incomplete in older patients. However, the mechanisms underlying poor recovery of aged muscle following disuse remain to be delineated. Recent evidence suggests that mitochondrial energetics play an important role in regulation of muscle mass. To this end, we employed multiple approaches to address the role of mitochondrial function and metabolism in muscle atrophy and sarcopenia. And we are also engaged to develop novel mitochondria-targeted antioxidant peptides to mitigate this mitochondria-related functional impairment by ROS and improve the recovery from muscle atrophy and cachexia.&#x0D; Methods Tail Suspension Hind Limb Unloading for adult mice (6-month-old) and aged mice (22-24month old). Cardiometabolic Phenotyping：Measurement of fat and lean mass (g) is accomplished using a LF90II TD-NMR (Bruker, Madison, WI). Locomotor activity measurements are obtained using a Promethion Mouse Multiplexed Metabolic System(Sable Systems International, Las Vegas, NV).Mitochondrial Respiration :Respirometry assays were conducted using an Oxygraph-2k (Oroboros Instruments, Innsbruck, Austria), Mitochondria H2O2 emission was measured with Amplex Red reagent which reacts with H2O2 to produce the stable fluorescent compound resorufin. Resorufin fluorescence was monitored using a Fluorescence. A continuous, spectrophotometric assay was utilized to measure mitochondrial calcium retention capacity (CRC) within soleus fiber bundles. RNA Sequencing and Informatics, KEGG Pathway and Upstream Regulator Analysis, Real-Time Quantitative-PCR. Multidimensional mass spectrometry-based shotgun lipidomics was employed to measure and characterize the lipid patterns inmouse soleus muscle. Metabolomics Acylcarnitines A panel of acylcarnitines was quantitated by LC/ MS/MS (Agilent 1290 HPLC/6490 triple quadrupole mass spectrometer). Amino Acids. Quantitation of amino acids was achieved using LC/MS/MS (Agilent 1290 HPLC/6490 triple quadrupole mass spectrometer).&#x0D; Results Old mice have impaired early recovery of soleus mass following unloading induced muscle atrophy. And mitochondrial function and metabolism does not Improve during early recovery in aged Mice. Divergent metabolomic response was found between adult and aged Mice during unloading and recovery. However, transcriptomic response to unloading and reloading is similar in adult and aged Mice.&#x0D; Conclusions Here, we report that aged mice with low muscle mass and low glucose clearance rate also display poor early recovery of muscle mass after disuse muscle atrophy. We used unbiased and targeted approaches to identify changes in energy metabolism gene expression, metabolite pools and mitochondrial phenotype and show for the first time that persistent mitochondrial dysfunction, dysregulated fatty acid β-oxidation and elevated H2O2 emission occur concomitantly with poor early recovery of muscle mass following a period of disuse in old mice. Importantly, this is linked to more severe whole-body insulin resistance, as determined by insulin tolerance test. Our findings also showed cellular metabolic changes during muscle atrophy and sarcopenia may induce higher production of oxygen radicals that play a significant role in the progression of age-related sarcopenia. These findings suggest that muscle fuel metabolism and mitochondrial energetics could be a focus for mining therapeutic targets to improve recovery of muscle mass following periods of disuse. We are engaged to develop novel mitochondria-targeted antioxidant peptides to mitigate this mitochondria-related functional impairment by ROS and improve the recovery from muscle atrophy and cachexia. Co-administration of other targeted compounds was also promising to improve recovery from muscle atrophy and cachexia.&#x0D;

Actifield, an automated open source actimeter for rodents

Abstract Locomotor activity in rodents is routinely assessed in the evaluation of drugs and other behavioural studies. Several proprietary lab equipment are available to measure locomotion, however their prohibitive cost may pose a challenge to newly-established and poorly funded labs. To overcome this challenge we present Actifield, an open source hardware setup to measure locomotor activity in rodents. The design consists of 3D printed and laser-cut parts as well as “off-the-shelf” electronic components. Here we demonstrate that rodent locomotor activity can be recorded using the IR motion detection system employed in Actifield. Moreover, we show in validation experiments that this hardware system is comparable to commercial and open source video tracking systems. Actifield would be particularly useful to labs in need of a reliable and inexpensive equipment that can be easily built.

Root bark of Discaria americana attenuates pain: A pharmacological evidence of interaction with opioidergic system and TRP/ASIC channels

Ethnopharmacological relevanceDiscaria americana (Rhamnaceae) root bark infusion have been used in traditional medicine as antipyretic, tonic, ameliorative of stomach and skin diseases and diabetes. This study was designed to investigate whether the methanolic extract of the root bark of Discaria americana (MEDa) exhibits antinociceptive effects in mice. Furthermore, it was investigated the involvement of the opioidergic system in MEDa mechanism of action as well the interactions with TRP/ASIC channels in its effect. Materials and methodsThe antinociceptive effect of intra-gastric gavage (i.g.) of MEDa (0.3–300 mg/kg) was evaluated in mice subjected to acute chemical (acetic-acid, formalin, glutamate, capsaicin, cinnamaldehyde, and acidified saline) or thermal (hot plate) tests of pain. The involvement of opioid system was evaluated in the formalin test. A nonspecific effect of MEDa was observed by measuring locomotor activity and exploratory behavior in open field test. ResultsMEDa significantly reduced the number of writhing induced by acetic acid and inhibited the nociception in the two phases of formalin. These effects were inhibited by pretreatment with naloxone. The nociception induced by hot plate and intraplantar injection of glutamate, capsaicin, cinnamaldehyde and acidified saline were significantly inhibited by MEDa. Only the dose of 300 mg/kg altered the locomotor activity. ConclusionsOur results demonstrated, for the first time, that the methanolic extract of the root bark of Discaria americana presents antinociceptive effect in chemical and thermal stimuli and its analgesic properties can be due activation of the opioidergic system. These results support the use of Discaria americana in traditional medicine and demonstrate that this plant presents a therapeutic potential for the development of phytomedicines with antinociceptive profile.