ResearchPad - rodents https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Thalamic, cortical, and amygdala involvement in the processing of a natural sound cue of danger]]> https://www.researchpad.co/article/elastic_article_7872 When others stop and silence ensues, animals respond as if threatened. This study highlights the brain areas involved in listening to the dangerous silence.

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<![CDATA[Methamphetamine administration increases hepatic CYP1A2 but not CYP3A activity in female guinea pigs]]> https://www.researchpad.co/article/elastic_article_7848 Methamphetamine use has increased over the past decade and the first use of methamphetamine is most often when women are of reproductive age. Methamphetamine accumulates in the liver; however, little is known about the effect of methamphetamine use on hepatic drug metabolism. Methamphetamine was administered on 3 occassions to female Dunkin Hartley guinea pigs of reproductive age, mimicking recreational drug use. Low doses of test drugs caffeine and midazolam were administered after the third dose of methamphetamine to assess the functional activity of cytochrome P450 1A2 and 3A, respectively. Real-time quantitative polymerase chain reaction was used to quantify the mRNA expression of factors involved in glucocorticoid signalling, inflammation, oxidative stress and drug transporters. This study showed that methamphetamine administration decreased hepatic CYP1A2 mRNA expression, but increased CYP1A2 enzyme activity. Methamphetamine had no effect on CYP3A enzyme activity. In addition, we found that methamphetamine may also result in changes in glucocorticoid bioavailability, as we found a decrease in 11β-hydroxysteroid dehydrogenase 1 mRNA expression, which converts inactive cortisone into active cortisol. This study has shown that methamphetamine administration has the potential to alter drug metabolism via the CYP1A2 metabolic pathway in female guinea pigs. This may have clinical implications for drug dosing in female methamphetamine users of reproductive age.

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<![CDATA[Effects of scent lure on camera trap detections vary across mammalian predator and prey species]]> https://www.researchpad.co/article/elastic_article_7840 Camera traps are a unique survey tool used to monitor a wide variety of mammal species. Camera trap (CT) data can be used to estimate animal distribution, density, and behaviour. Attractants, such as scent lures, are often used in an effort to increase CT detections; however, the degree which the effects of attractants vary across species is not well understood. We investigated the effects of scent lure on mammal detections by comparing detection rates between 404 lured and 440 unlured CT stations sampled in Alberta, Canada over 120 day survey periods between February and August in 2015 and 2016. We used zero-inflated negative binomial generalized linear mixed models to test the effect of lure on detection rates for a) all mammals, b) six functional groups (all predator species, all prey, large carnivores, small carnivores, small mammals, ungulates), and c) four varied species of management interest (fisher, Pekania pennanti; gray wolf, Canis lupus; moose, Alces alces; and Richardson’s ground squirrel; Urocitellus richardsonii). Mammals were detected at 800 of the 844 CTs, with nearly equal numbers of total detections at CTs with (7110) and without (7530) lure, and variable effects of lure on groups and individual species. Scent lure significantly increased detections of predators as a group, including large and small carnivore sub-groups and fisher specifically, but not of gray wolf. There was no effect of scent lure on detections of prey species, including the small mammal and ungulate sub-groups and moose and Richardson’s ground squirrel specifically. We recommend that researchers explicitly consider the variable effects of scent lure on CT detections across species when designing, interpreting, or comparing multi-species surveys. Additional research is needed to further quantify variation in species responses to scent lures and other attractants, and to elucidate the effect of attractants on community-level inferences from camera trap surveys.

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<![CDATA[Exposure to dim light at night prior to conception attenuates offspring innate immune responses]]> https://www.researchpad.co/article/N231fece1-eb24-47b2-a00f-cbdce7a093c6

Functional circadian timekeeping is necessary for homeostatic control of the immune system and appropriate immune responsiveness. Disruption of natural light-dark cycles, through light at night (LAN), impairs innate and adaptive immune responses in nocturnal rodents. These altered immune responses are associated with disrupted endogenous gene transcriptional and endocrine cycles. However, few studies have addressed the multigenerational consequences of systemic circadian rhythm disruption. We hypothesized that parental exposure to dim LAN (dLAN) would alter innate immune and sickness responses to an endotoxin challenge in adult offspring gestated and reared in dark nights. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 8 weeks, then paired, mated, and thereafter housed under dark nights. Maternal exposure to dLAN prior to conception impaired febrile responses and increased splenic il-1 production in response to LPS in male offspring. Paternal pre-conception dLAN dampened offspring tnf-α expression in the hypothalamus, reduced serum bactericidal capacity, and dark phase locomotor activity. These changes occurred despite offspring being conceived, gestated, and reared under standard dark night conditions. Overall, these data suggest that dLAN has intergenerational effects on innate immunity and sickness responses.

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<![CDATA[Neuroprotective effects of exogenous erythropoietin in Wistar rats by downregulating apoptotic factors to attenuate N-methyl-D-aspartate-mediated retinal ganglion cells death]]> https://www.researchpad.co/article/N85685bba-c047-422b-abfc-358a98ed1fe7

The aim of this study was to investigate whether exogenous erythropoietin (EPO) administration attenuates N-methyl-D-aspartate (NMDA)-mediated excitotoxic retinal damage in Wistar rats. The survival rate of retinal ganglion cells (RGCs) were investigated by flat mount analysis and flow cytometry. A total of 125 male Wistar rats were randomly assigned to five groups: negative control, NMDA80 (i.e., 80 nmoles NMDA intravitreally injected), NMDA80 + 10ng EPO, NMDA80 + 50ng EPO, and NMDA80 + 250ng EPO. The NMDA80 + 50ng EPO treatment group was used to evaluate various administrated points (pre-/co-/post- administration of NMDA80). Meanwhile, the transferase dUTP Nick-End Labeling (TUNEL) assay of RGCs, the inner plexiform layer (IPL) thickness and the apoptotic signal transduction pathways of μ-calpain, Bax, and caspase 9 were assessed simultaneously using an immunohistochemical method (IHC). When EPO was co-administered with NMDA80, attenuated cell death occurred through the downregulation of the apoptotic indicators: μ-calpain was activated first (peak at ~18hrs), followed by Bax and caspase 9 (peak at ~40hrs). Furthermore, the images of retinal cross sections have clearly demonstrated that thickness of the inner plexiform layer (IPL) was significantly recovered at 40 hours after receiving intravitreal injection with NMDA80 and 50ng EPO. Exogenous EPO may protect RGCs and bipolar cell axon terminals in IPL by downregulating apoptotic factors to attenuate NMDA-mediated excitotoxic retinal damage.

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<![CDATA[Bilateral Parkinson’s disease model rats exhibit hyperalgesia to subcutaneous formalin administration into the vibrissa pad]]> https://www.researchpad.co/article/Nc1e56242-0f9e-4dec-b14c-0acf3482ec2d

We bilaterally injected 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle of rats and developed bilateral Parkinson’s disease (PD) model rats in order to experimentally investigate the neural mechanisms underlying the alteration of nociception in the orofacial region of patients with PD. We explored the effects of dopamine depletion on nociception by investigating behavioral responses (face rubbing) triggered by subcutaneous administration of formalin into the vibrissa pad. We also assessed the number of c-Fos–immunoreactive (c-Fos-IR) cells in the superficial layers of the trigeminal spinal subnucleus caudalis (Vc). Subcutaneous formalin administration evoked a two-phase increase in face rubbing. We observed the first increase 0–5 min after formalin administration (first phase) and the second increase 10–60 min after administration (second phase). The number of face rubbing behaviors of 6OHDA–injected rats did not significantly change compared with saline–injected rats in both phases. Significant increase of c-Fos-IR cells in the Vc was found in 6-OHDA–injected rats after formalin administration compared with those in saline–injected rats after formalin administration. We also assessed expression of c-Fos-IR cells in the paraventricular nucleus (PVN), and significant decrease of c-Fos-IR cells in the PVN of 6-OHDA–injected rats was found. Taken together, these findings suggest that bilateral dopaminergic denervation evoked by 6-OHDA administration causes hyperalgesia in the trigeminal region and the PVN may be involved in the hyperalgesia.

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<![CDATA[Characterization of an intratracheal aerosol challenge model of Brucella melitensis in guinea pigs]]> https://www.researchpad.co/article/5c8823ccd5eed0c48463903c

B. melitensis is considered the most virulent of the Brucella species, and a need exists for an improved laboratory animal model of infection that mimics natural transmission and disease. Guinea pigs are highly susceptible to infection with Brucella spp. and develop a disease syndrome that mimics natural disease after aerosol inoculation. Intratracheal inoculation is a targeted means of generating aerosols that offer advantages over aerosol chamber delivery. To establish this delivery method, female, Hartley guinea pigs were infected via intratracheal inoculation with PBS or 16M B. melitensis at low dose (101 to 103) or high dose (106 to 108) and monitored for 30 days for signs of disease. Guinea pigs in the high dose groups developed fever between 12–17 days post-inoculation. Bacteria were recovered from the spleen, liver, lymph nodes, lung, and uterus at 30-days post-inoculation and demonstrated dose dependent mean increases in colonization and pathologic changes consistent with human brucellosis. To study the kinetics of extrapulmonary dissemination, guinea pigs were inoculated with 107 CFU and euthanized at 2-hours post inoculation and at weekly intervals for 3 weeks. 5.8x105 to 4.2x106 CFU were recovered from the lung 2 hours post-inoculation indicating intratracheal inoculation is an efficient means of infecting guinea pigs. Starting at 1-week post inoculation bacteria were recovered from the aforementioned organs with time dependent mean increases in colonization. This data demonstrates that guinea pigs develop a disease syndrome that models the human manifestation of brucellosis, which makes the guinea pig a valuable model for pathogenesis studies.

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<![CDATA[AutonoMouse: High throughput operant conditioning reveals progressive impairment with graded olfactory bulb lesions]]> https://www.researchpad.co/article/5c897775d5eed0c4847d2d5d

Operant conditioning is a crucial tool in neuroscience research for probing brain function. While molecular, anatomical and even physiological techniques have seen radical increases in throughput, efficiency, and reproducibility in recent years, behavioural tools have somewhat lagged behind. Here we present a fully automated, high-throughput system for self-initiated conditioning of up to 25 group-housed, radio-frequency identification (RFID) tagged mice over periods of several months and >106 trials. We validate this “AutonoMouse” system in a series of olfactory behavioural tasks and show that acquired data is comparable to previous semi-manual approaches. Furthermore, we use AutonoMouse to systematically probe the impact of graded olfactory bulb lesions on olfactory behaviour, demonstrating that while odour discrimination in general is robust to even most extensive disruptions, small olfactory bulb lesions already impair odour detection. Discrimination learning of similar mixtures as well as learning speed are in turn reliably impacted by medium lesion sizes. The modular nature and open-source design of AutonoMouse should allow for similar robust and systematic assessments across neuroscience research areas.

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<![CDATA[Social isolation produces no effect on ultrasonic vocalization production in adult female CBA/CaJ mice]]> https://www.researchpad.co/article/5c8823d4d5eed0c4846390e2

Mice produce ultrasonic vocalizations (USVs) in a wide variety of social contexts, including courtship, investigation, and territorial defense. Despite the belief that mouse USVs are innate, social experience may be necessary for mice to learn the appropriate situation to emit USVs. Mouse USVs have been divided into categories based on their spectrotemporal parameters, but it is currently unclear if social experience changes these parameters (e.g., frequency and duration) or the proportion of calls from each category produced. Social isolation has been found to influence USV production in male mice. To investigate the influence of social isolation on vocal behavior in female mice, recordings were made of USVs emitted to unfamiliar male and female mice by subjects with one of three types of social experience. Twenty-four adult female CBA/CaJ mice either lived alone, lived with other females only, or lived with other females and had limited access to a male. Mice were recorded while in isolation, ensuring all recorded USVs were from the female of interest. Vocalizations were separated into nine categories and peak frequency, duration, and bandwidth were measured for every call. Socially isolated mice did not produce significantly more USVs or USV types than socially experienced mice. Social isolation did not have a significant effect on the features of USVs, suggesting production of USVs may not be learned in female mice.

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<![CDATA[Trpm4 ion channels in pre-Bötzinger complex interneurons are essential for breathing motor pattern but not rhythm]]> https://www.researchpad.co/article/5c784fa8d5eed0c484007252

Inspiratory breathing movements depend on pre-Bötzinger complex (preBötC) interneurons that express calcium (Ca2+)-activated nonselective cationic current (ICAN) to generate robust neural bursts. Hypothesized to be rhythmogenic, reducing ICAN is predicted to slow down or stop breathing; its contributions to motor pattern would be reflected in the magnitude of movements (output). We tested the role(s) of ICAN using reverse genetic techniques to diminish its putative ion channels Trpm4 or Trpc3 in preBötC neurons in vivo. Adult mice transduced with Trpm4-targeted short hairpin RNA (shRNA) progressively decreased the tidal volume of breaths yet surprisingly increased breathing frequency, often followed by gasping and fatal respiratory failure. Mice transduced with Trpc3-targeted shRNA survived with no changes in breathing. Patch-clamp and field recordings from the preBötC in mouse slices also showed an increase in the frequency and a decrease in the magnitude of preBötC neural bursts in the presence of Trpm4 antagonist 9-phenanthrol, whereas the Trpc3 antagonist pyrazole-3 (pyr-3) showed inconsistent effects on magnitude and no effect on frequency. These data suggest that Trpm4 mediates ICAN, whose influence on frequency contradicts a direct role in rhythm generation. We conclude that Trpm4-mediated ICAN is indispensable for motor output but not the rhythmogenic core mechanism of the breathing central pattern generator.

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<![CDATA[It’s a trap: Optimizing detection of rare small mammals]]> https://www.researchpad.co/article/5c8823a9d5eed0c484638d89

Improving detection probabilities for rare species is critical when assessing presence or habitat associations. Our goal was to create a new small mammal trapping protocol that improved detection of rare species, such as the olive-backed pocket mouse (Perognathus fasciatus). We used three trap and bait types and trapped an area 4.4 times larger than the standard grid. We also assessed the effect of captures of non-target species on detection probability of pocket mice. Regardless of species, trap success was higher for Havaharts. We found that bait and trap type selection varied significantly by species, with pocket mice showing strongest selection for Havahart traps baited with bird seed. Increasing grid size, while maintaining a similar trapping effort, resulted in higher detection probability, although our analyses showed that effective grids can be about three-quarters of the size we use to achieve similar results. We were also able to demonstrate that by deploying a combination of different traps and baits it is possible to overcome the potential effect of non-target species (e.g., deer mice, Peromyscus maniculatus) on the detection probability of pocket mice. Our results show that simple changes to standard small-mammal trapping methods can dramatically increase the detectability of rare and elusive small mammals. Increasing detection probability of rare components of a community can improve the results and understanding of future studies.

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<![CDATA[Posterior ventral tegmental area-nucleus accumbens shell circuitry modulates response to novelty]]> https://www.researchpad.co/article/5c8823b2d5eed0c484638e5a

Dopamine release in the nucleus accumbens from ventral tegmental area (VTA) efferent neurons is critical for orientation and response to novel stimuli in the environment. However, there are considerable differences between neuronal populations of the VTA and it is unclear which specific cell populations modulate behavioral responses to environmental novelty. A retroDREADDs (designer drugs exclusively activated by designer receptors) technique, comprising designer G protein-coupled receptors exclusively activated by designer drugs and modulated by retrograde transported Cre, was used to selectively stimulate neurons of the VTA which project to the nucleus accumbens shell (AcbSh). First, the selectivity and expression of the human M3 muscarinic receptor-based adeno-associated virus (AAV-hM3D) was confirmed in primary neuronal cell cultures. Second, AAV-CMV-GFP/Cre was infused into the AcbSh and AAV-hSyn-DIO-hM3D(Gq)-mCherry (a presynaptic enhancer in the presence of its cognate ligand clozapine-N-oxide) was infused into the VTA of ovariectomized female Fisher 344 rats to elicit hM3D(Gq)-mCherry production specifically in neurons of the VTA which synapse in the AcbSh. Finally, administration of clozapine-N-oxide significantly altered rodents’ response to novelty (e.g. absence of white background noise) by activation of hM3D(Gq) receptors, without altering gross locomotor activity or auditory processing per se. Confocal imaging confirmed production of mCherry in neurons of the posterior aspect of the VTA (pVTA) suggesting these neurons contribute to novelty responses. These results suggest the pVTA-AcbSh circuit is potentially altered in motivational disorders such as apathy, depression, and drug addiction. Targeting the pVTA-AcbSh circuit, therefore, may be an effective target for pharmacological management of such psychopathologies.

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<![CDATA[A computational model of epithelial solute and water transport along a human nephron]]> https://www.researchpad.co/article/5c7d95f0d5eed0c484734ff2

We have developed the first computational model of solute and water transport from Bowman space to the papillary tip of the nephron of a human kidney. The nephron is represented as a tubule lined by a layer of epithelial cells, with apical and basolateral transporters that vary according to cell type. The model is formulated for steady state, and consists of a large system of coupled ordinary differential equations and algebraic equations. Model solution describes luminal fluid flow, hydrostatic pressure, luminal fluid solute concentrations, cytosolic solute concentrations, epithelial membrane potential, and transcellular and paracellular fluxes. We found that if we assume that the transporter density and permeabilities are taken to be the same between the human and rat nephrons (with the exception of a glucose transporter along the proximal tubule and the H+-pump along the collecting duct), the model yields segmental deliveries and urinary excretion of volume and key solutes that are consistent with human data. The model predicted that the human nephron exhibits glomerulotubular balance, such that proximal tubular Na+ reabsorption varies proportionally to the single-nephron glomerular filtration rate. To simulate the action of a novel diabetic treatment, we inhibited the Na+-glucose cotransporter 2 (SGLT2) along the proximal convoluted tubule. Simulation results predicted that the segment’s Na+ reabsorption decreased significantly, resulting in natriuresis and osmotic diuresis.

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<![CDATA[Probabilistic logic analysis of the highly heterogeneous spatiotemporal HFRS incidence distribution in Heilongjiang province (China) during 2005-2013]]> https://www.researchpad.co/article/5c5ca2d1d5eed0c48441eb6c

Background

Hemorrhagic fever with renal syndrome (HFRS) is a zoonosis caused by hantavirus (belongs to Hantaviridae family). A large amount of HFRS cases occur in China, especially in the Heilongjiang Province, raising great concerns regarding public health. The distribution of these cases across space-time often exhibits highly heterogeneous characteristics. Hence, it is widely recognized that the improved mapping of heterogeneous HFRS distributions and the quantitative assessment of the space-time disease transition patterns can advance considerably the detection, prevention and control of epidemic outbreaks.

Methods

A synthesis of space-time mapping and probabilistic logic is proposed to study the distribution of monthly HFRS population-standardized incidences in Heilongjiang province during the period 2005–2013. We introduce a class-dependent Bayesian maximum entropy (cd-BME) mapping method dividing the original dataset into discrete incidence classes that overcome data heterogeneity and skewness effects and can produce space-time HFRS incidence estimates together with their estimation accuracy. A ten-fold cross validation analysis is conducted to evaluate the performance of the proposed cd-BME implementation compared to the standard class-independent BME implementation. Incidence maps generated by cd-BME are used to study the spatiotemporal HFRS spread patterns. Further, the spatiotemporal dependence of HFRS incidences are measured in terms of probability logic indicators that link class-dependent HFRS incidences at different space-time points. These indicators convey useful complementary information regarding intraclass and interclass relationships, such as the change in HFRS transition probabilities between different incidence classes with increasing geographical distance and time separation.

Results

Each HFRS class exhibited a distinct space-time variation structure in terms of its varying covariance parameters (shape, sill and correlation ranges). Given the heterogeneous features of the HFRS dataset, the cd-BME implementation demonstrated an improved ability to capture these features compared to the standard implementation (e.g., mean absolute error: 0.19 vs. 0.43 cases/105 capita) demonstrating a point outbreak character at high incidence levels and a non-point spread character at low levels. Intraclass HFRS variations were found to be considerably different than interclass HFRS variations. Certain incidence classes occurred frequently near one class but were rarely found adjacent to other classes. Different classes may share common boundaries or they may be surrounded completely by another class. The HFRS class 0–68.5% was the most dominant in the Heilongjiang province (covering more than 2/3 of the total area). The probabilities that certain incidence classes occur next to other classes were used to estimate the transitions between HFRS classes. Moreover, such probabilities described the dependency pattern of the space-time arrangement of HFRS patches occupied by the incidence classes. The HFRS transition probabilities also suggested the presence of both positive and negative relations among the main classes. The HFRS indicator plots offer complementary visualizations of the varying probabilities of transition between incidence classes, and so they describe the dependency pattern of the space-time arrangement of the HFRS patches occupied by the different classes.

Conclusions

The cd-BME method combined with probabilistic logic indicators offer an accurate and informative quantitative representation of the heterogeneous HFRS incidences in the space-time domain, and the results thus obtained can be interpreted readily. The same methodological combination could also be used in the spatiotemporal modeling and prediction of other epidemics under similar circumstances.

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<![CDATA[Secondary contact between diverged host lineages entails ecological speciation in a European hantavirus]]> https://www.researchpad.co/article/5c76fdefd5eed0c484e5b0f1

The diversity of viruses probably exceeds biodiversity of eukaryotes, but little is known about the origin and emergence of novel virus species. Experimentation and disease outbreak investigations have allowed the characterization of rapid molecular virus adaptation. However, the processes leading to the establishment of functionally distinct virus taxa in nature remain obscure. Here, we demonstrate that incipient speciation in a natural host species has generated distinct ecological niches leading to adaptive isolation in an RNA virus. We found a very strong association between the distributions of two major phylogenetic clades in Tula orthohantavirus (TULV) and the rodent host lineages in a natural hybrid zone of the European common vole (Microtus arvalis). The spatial transition between the virus clades in replicated geographic clines is at least eight times narrower than between the hybridizing host lineages. This suggests a strong barrier for effective virus transmission despite frequent dispersal and gene flow among local host populations, and translates to a complete turnover of the adaptive background of TULV within a few hundred meters in the open, unobstructed landscape. Genetic differences between TULV clades are homogenously distributed in the genomes and mostly synonymous (93.1%), except for a cluster of nonsynonymous changes in the 5′ region of the viral envelope glycoprotein gene, potentially involved in host-driven isolation. Evolutionary relationships between TULV clades indicate an emergence of these viruses through rapid differential adaptation to the previously diverged host lineages that resulted in levels of ecological isolation exceeding the progress of speciation in their vertebrate hosts.

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<![CDATA[Nuclear position relative to the Golgi body and nuclear orientation are differentially responsive indicators of cell polarized motility]]> https://www.researchpad.co/article/5c6dca31d5eed0c48452a8a8

Cell motility is critical to biological processes from wound healing to cancer metastasis to embryonic development. The involvement of organelles in cell motility is well established, but the role of organelle positional reorganization in cell motility remains poorly understood. Here we present an automated image analysis technique for tracking the shape and motion of Golgi bodies and cell nuclei. We quantify the relationship between nuclear orientation and the orientation of the Golgi body relative to the nucleus before, during, and after exposure of mouse fibroblasts to a controlled change in cell substrate topography, from flat to wrinkles, designed to trigger polarized motility. We find that the cells alter their mean nuclei orientation, in terms of the nuclear major axis, to increasingly align with the wrinkle direction once the wrinkles form on the substrate surface. This change in alignment occurs within 8 hours of completion of the topographical transition. In contrast, the position of the Golgi body relative to the nucleus remains aligned with the pre-programmed wrinkle direction, regardless of whether it has been fully established. These findings indicate that intracellular positioning of the Golgi body precedes nuclear reorientation during mouse fibroblast directed migration on patterned substrates. We further show that both processes are Rho-associated kinase (ROCK) mediated as they are abolished by pharmacologic ROCK inhibition whereas mouse fibroblast motility is unaffected. The automated image analysis technique introduced could be broadly employed in the study of polarization and other cellular processes in diverse cell types and micro-environments. In addition, having found that the nuclei Golgi vector may be a more sensitive indicator of substrate features than the nuclei orientation, we anticipate the nuclei Golgi vector to be a useful metric for researchers studying the dynamics of cell polarity in response to different micro-environments.

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<![CDATA[In vivo positron emission tomographic blood pool imaging in an immunodeficient mouse model using 18F-fluorodeoxyglucose labeled human erythrocytes]]> https://www.researchpad.co/article/5c57e690d5eed0c484ef3751

99m-Technetium-labeled (99mTc) erythrocyte imaging with planar scintigraphy is widely used for evaluating both patients with occult gastrointestinal bleeding and patients at risk for chemotherapy-induced cardiotoxicity. While a number of alternative radionuclide-based blood pool imaging agents have been proposed, none have yet to achieve widespread clinical use. Here, we present both in vitro and small animal in vivo imaging evidence that the high physiological expression of the glucose transporter GLUT1 on human erythrocytes allows uptake of the widely available radiotracer 2-deoxy-2-(18F)fluoro-D-glucose (FDG), at a rate and magnitude sufficient for clinical blood pool positron emission tomographic (PET) imaging. This imaging technique is likely to be amenable to rapid clinical translation, as it can be achieved using a simple FDG labeling protocol, requires a relatively small volume of phlebotomized blood, and can be completed within a relatively short time period. As modern PET scanners typically have much greater count detection sensitivities than that of commonly used clinical gamma scintigraphic cameras, FDG-labeled human erythrocyte PET imaging may not only have significant advantages over 99mTc-labeled erythrocyte imaging, but may have other novel blood pool imaging applications.

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<![CDATA[Kami-shoyo-san improves ASD-like behaviors caused by decreasing allopregnanolone biosynthesis in an SKF mouse model of autism]]> https://www.researchpad.co/article/5c5ca2dcd5eed0c48441ebe8

Dysfunctions in the GABAergic system are associated with the pathogenesis of autism spectrum disorder (ASD). However, the mechanisms by which GABAergic system dysfunctions induce the pathophysiology of ASD remain unclear. We previously demonstrated that a selective type I 5α-reductase inhibitor SKF105111 (SKF) induced ASD-like behaviors, such as impaired sociability-related performance and repetitive grooming behaviors, in male mice. Moreover, the effects of SKF were caused by a decrease in the endogenous levels of allopregnanolone (ALLO), a positive allosteric modulator of the GABAA receptor. In this study, we used SKF-treated male mice as a putative animal model of ASD and examined the effects of Kami-shoyo-san (KSS) as an experimental therapeutic strategy for ASD. KSS is a traditional Kampo formula consisting of 10 different crude drugs and has been used for the treatment of neuropsychiatric symptoms. KSS dose-dependently attenuated sociability deficits and suppressed an increase in grooming behaviors in SKF-treated mice without affecting ALLO content in the prefrontal cortex. The systemic administration of the dopamine D1 receptor antagonist SCH23390 reversed the ameliorative effects of KSS. On the other hand, the dopamine D2 receptor antagonist sulpiride and GABAA receptor antagonist bicuculline only attenuated the ameliorative effect of KSS on repetitive self-grooming behaviors. The present results indicate that KSS improves SKF-induced ASD-like behaviors by facilitating dopamine receptor-mediated mechanisms and partly by neurosteroid-independent GABAA receptor-mediated neurotransmission. Therefore, KSS is a potential candidate for the treatment of ASD.

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<![CDATA[Nitrogen gas produces less behavioural and neurophysiological excitation than carbon dioxide in mice undergoing euthanasia]]> https://www.researchpad.co/article/5c5ca2bcd5eed0c48441e9d5

Carbon dioxide (CO2) is one of the most commonly used gas euthanasia agents in mice, despite reports of aversion and nociception. Inert gases such as nitrogen (N2) may be a viable alternative to carbon dioxide. Here we compared behavioural and electrophysiological reactions to CO2 or N2 at either slow fill or rapid fill in C57Bl/6 mice undergoing gas euthanasia. We found that mice euthanised with CO2 increased locomotor activity compared to baseline, whereas mice exposed to N2 decreased locomotion. Furthermore, mice exposed to CO2 showed significantly more vertical jumps and freezing episodes than mice exposed to N2. We further found that CO2 exposure resulted in increased theta:delta of the EEG, a measure of excitation, whereas the N2 decreased theta:delta. Differences in responses were not oxygen-concentration dependent. Taken together, these results demonstrate that CO2 increases both behavioural and electrophysiological excitation as well as producing a fear response, whereas N2 reduces behavioural activity and central neurological depression and may be less aversive although still produces a fear response. Further studies are required to evaluate N2 as a suitable euthanasia agent for mice.

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<![CDATA[Sleeping through anything: The effects of unpredictable disruptions on mouse sleep, healing, and affect]]> https://www.researchpad.co/article/5c5ca2b9d5eed0c48441e977

Many aspects of the laboratory environment are not tailored to the needs of rodents, which may cause stress. Unpredictable stressors can cause ulcers, prolonged pituitary-adrenal activation, and anhedonia. Similarly, pain has been demonstrated to slow wound healing, and mice experiencing pain exhibit altered behavior. However it is unknown how husbandry, which occurs when the mice are inactive, and lack of analgesia, specifically in a punch biopsy procedure, effects animal physiology, behavior, and welfare, particularly as it relates to sleep fragmentation. We hypothesized that sleep fragmentation, induced by unpredictable husbandry and lack of pain management will slow wound healing. Two main treatments were tested in a factorial design in C57BL/6 mice of both sexes (64 mice total); 1) analgesia (carprofen and saline) and 2) sleep disruptions (random and predictable). Mice were singly housed in a non-invasive sleep monitoring apparatus on arrival (Day -4). Disruption treatments were applied from Day -3 to 2. All mice received a punch biopsy surgery (Day 0) with topical lidocaine gel and their analgesic treatment prior to recovery, and on Days 1 and 2. Nesting behavior was assessed daily and a sugar cereal consumption test, as a measure of anhedonia, was conducted on Days -1 to 2. On Day 3, mice were euthanized and wound tissue and adrenal glands were collected. We found that the disruption predictability had no effect on mouse sleep, wound healing, or adrenal cortex:medulla ratio. It’s possible that the disruption period was not long enough to induce chronic stress. However, male mice who received analgesia slept more than their female counterparts; this may be related to sex differences in pain perception. Overall, it does not appear that the predictability of disturbance effects sleep fragmentation or stress responses, indicating that husbandry activities do not need to occur at set predictable times to improve welfare.

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