Chronic long-term exposure to cuprizone causes severe brain demyelination in mice,which leads to changes in locomotion,working memory and anxiety.These findings suggest the importance of intact myelin for these behavi...Chronic long-term exposure to cuprizone causes severe brain demyelination in mice,which leads to changes in locomotion,working memory and anxiety.These findings suggest the importance of intact myelin for these behaviors.This study aimed to investigate the possible behavioral changes in mice with mild oligodendrocyte/myelin damage that parallels the white matter changes seen in the brains of patients with psychiatric disporders.We used the cuprizonetreated mouse model to test both tissue changes and behavioral functions（locomotor activity,anxiety status,and spatial working memory）.The results showed that mice given cuprizone in their diet for 7 days had no significant myelin breakdown as evaluated by immunohistochemical staining for myelin basic protein,while the number of mature oligodendrocytes was reduced.The number and length of Caspr protein clusters,a structural marker of the node of Ranvier,did not change.The locomotor activity of the cuprizonetreated mice increased whereas their anxiety levels were lower than in normal controls;spatial working memory,however,did not change.These results,for the first time,link emotion-related behavior with mild white matter damage in cuprizone-treated mice.展开更多
Human activities involving noise emission can affect wild animals.European mink was exposed to road noise and human voice playbacks to analyze how sound intensity level and duration of both noises altered the time tha...Human activities involving noise emission can affect wild animals.European mink was exposed to road noise and human voice playbacks to analyze how sound intensity level and duration of both noises altered the time that individuals were active and if their fecal cortisol metabolite(FCM)levels varied.A Hierarchical Analysis Cluster was performed to establish 2 mink groups with respect to both noise source type:short duration/low intensity(SL)and long duration/high intensity(LH).We performed general linear mixed models to evaluate the variation in locomotor activity duration(s)and FCM(nanogram per gram)levels,respectively.The results showed both road noise and human voices decreased locomotor activity duration in SL more sharply compared with LH,and human voices were the triggers that induced the most pronounced response to both exposure conditions.FCM(ng/g)levels increased in SL compared with LH during road noise while the opposite happened during human voices.Differences based on sex and age of individuals were observed.In conclusion,noise characteristics given by the sound type determined the variations in locomotor activity duration while noise exposure level determined the variations in FCM(ng/g)levels.Attention should be paid to noisy activities(e.g.,recreational activities for visitors in protected natural areas)and loud groups of people to conserve wildlife,especially noise sensitive species.展开更多
The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was...The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's cover.Then,the RJ25 adaptor relayed the running signal to the main control board.Finally,the main control board was connected to the USB port of the computer with the USB connection.Data were collected using the online-accessible,self-created software Magturning.Through Magturning,generated data were saved and exported in real time.Afterward,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light conditions.In conclusion,this new device can record circadian activity of rodents.Our device is appropriate for interdisciplinary investigations related to biological clock research.展开更多
The three-dimensional organization of the genome plays a crucial role in regulating gene expression patterns in metazoans（Ong and Corces,2014）.The nuclear architectural proteins are known to facilitate the formation...The three-dimensional organization of the genome plays a crucial role in regulating gene expression patterns in metazoans（Ong and Corces,2014）.The nuclear architectural proteins are known to facilitate the formation of topological domains within the genome through mediating inter-and intra-chromosomal interactions.In vertebrate,CCCTC-binding factor（CTCF）is the main architectural protein that mediates long-range chromosomal interactions among its DNA binding sites through a process that is stabilized by cohesin （Parelho et al., 2008; Wendt et al., 2008）.展开更多
Valproic acid (VPA) is used in the treatment of epilepsy and behavioral disorders. However, the exposure to VPA during pregnancy increases the risk of having offspring with autism spectrum disorder (ASD). Reports indi...Valproic acid (VPA) is used in the treatment of epilepsy and behavioral disorders. However, the exposure to VPA during pregnancy increases the risk of having offspring with autism spectrum disorder (ASD). Reports indicate that men are more likely to suffer ASD than women who were exposed to VPA prenatally. Few studies have related the sex differences and behavioral changes in the ASD rat model. Our aim was to determinate whether male and female Wistar rats whose mothers were exposed to either VPA (600 mg/kg;animal model for ASD) or saline (0.9%) i.p. at 12.5 day of gestation, have different effects on immobility induce by clamping (IC), dorsal immobility (DI), catalepsy, locomotor activity, stereotypes, and analgesia (tail flick). For this purpose, we made four groups (n = 8). Group: A) saline male rats, B) saline female rats, C) VPA male rats and D) VPA female rats. At 35 (prepubertal age), 56 (postpubertal age) and 180 days, we tested the behaviors previously mentioned. Finding that VPA has the same effect on IC, catalepsy, and analgesia in male and female rats, the time of these tests was increased. However, VPA only has an effect on DI in males but not in female rats. On the contrary, there is hyperactivity and an increase of stereotypes in female but not in male rats. Thereby, VPA has an effect on the three immobility responses tested (IC, DI and catalepsy), locomotor activity and analgesia but in a differential way on DI, stereotypes and locomotor activity between male and female rats.展开更多
Estrogens are well known to increase locomotor activity in laboratory rodents;however,the underlying mechanism remains unclear.We used voluntary wheel running by female rats as an index of locomotor behavior to invest...Estrogens are well known to increase locomotor activity in laboratory rodents;however,the underlying mechanism remains unclear.We used voluntary wheel running by female rats as an index of locomotor behavior to investigate this issue.We first determined whether the estrogen-induced increase in locomotion was susceptible to inhibition by a physiological challenge,and next whether it was associated with dopaminergic activation in the central reward area,nucleus accumbens.Ovariectomized rats were given estradiol or the oil vehicle and housed in cages with or without running wheels.All rats were given regular rodent chow for 1 week,a sodium-deficient diet for the next week,and then were returned to a regular diet for another week.At the end of the last week,all rats were killed,brains were extracted and dopamine levels in the nucleus accumbens were measured.As expected,estradiol treatment increased distance run.Surprisingly,dietary sodium deprivation further increased running,but this appeared to be related to experience with wheel running,rather than to sodium deprivation,per se.Dopamine was greater in the nucleus accumbens of estradiol-treated rats that ran compared to all other groups.Thus,the estrogen-induced increase in locomotion is a robust phenomenon that is not inhibited by a body sodium challenge and is associated with elevated levels of dopamine in reward pathways.These findings raise the possibility that the estrogen-induced increase in locomotor activity,which occurs during a hormonal milieu conducive to reproduction,may reflect mate-seeking behavior and,thereby,maximize reproductive success.展开更多
Consistent inter-individual differences in daily activity rhythms(i.e.,chronotypes)can have ecological consequences in determining access to food resources and avoidance of predators.The most common measure to charact...Consistent inter-individual differences in daily activity rhythms(i.e.,chronotypes)can have ecological consequences in determining access to food resources and avoidance of predators.The most common measure to characterize chronotypes in animals as well as humans is the onset of activity(i.e.,early or late chronotypes).However,daily activity rhythms may also differ in the relative amount of activity displayed at particular time periods.Moreover,chronotypes may also be linked to other consistent inter-individual differences in behavior(i.e.,personality),such as the propensity to take risks.Here,we used the signal crayfish Pacifastacus leniusculusto test the presence of chronotypes and risk-taking personality traits and a potential behavioral syndrome between these traits.We first exposed crayfish to 5 days of light-darkness to measure daily activity rhythms and then we applied a visual predator-simulating stimulus in 2 different contexts(neutral and food).Our results showed consistent(i.e.,across 5 days)inter-individual differences in the relative nocturnal activity displayed in the early and middle,but not in the late part of darkness hours.Moreover,while crayfish displayed inter-individual differences in risk-taking behavior,these were not found to be consistent across 2 contexts.Therefore,we were not able to formally test a behavioral syndrome between these 2 traits.In conclusion,our study provides the first evidence of chronotypes in the relative amount of activity displayed at particular time periods.This could be a valuable information for applied ecological aspects related to the signal crayfish,which is a major invasive species of freshwater ecosystems.展开更多
The study of temperament and behavioral syndromes in insects is still in its early stage,and research conducted to date has mainly focused on locomotor activity and thanatosis.Dung beetles have been the subject of ext...The study of temperament and behavioral syndromes in insects is still in its early stage,and research conducted to date has mainly focused on locomotor activity and thanatosis.Dung beetles have been the subject of extensive behavioral studies;however,very few studies have addressed the expression of temperament.Those doing so only looked at subsocial and sexual horn dimorphic species,suggesting subsociality and/or sexual horn-dimorphism as possible facilitators of temperament expression.To test this assumption,we conducted a temperament study in a hornless,non-subsocial species,namely Geotrupes mutator(Marsham,1802).We set up laboratory tests to evaluate 3 behaviors(activity,thanatosis,and distress calls)through the measurement of 7 distinct behavioral traits(3 activity-,1 thanatosis-,and 3 call-related traits).We found high levels of individual repeatability in all activity-and thanatosis-related traits.We also identified behavioral differences between individuals,which may reflect differences in temperament.Statistical analyses revealed a negative correlation between activity and thanatosis.These results show that the temperament and behavioral syndromes related to activity and thanatosis may also be expressed in dung beetle species that are neither subsocial nor sexual horn dimorphic.By contrast,we only found one of 3 sound-related traits tested(frequency)to be clearly repeatable.Males and females presented a different structure of the stridulatory apparatus,suggesting that morphology may affect the frequency of sounds emitted.These results indicate that certain sound traits might not be good descriptors of individual temperament revealing the need for future research addressing the role of bioacoustics.展开更多
Objective To investigate the effect of M5 muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it＇s effect on the FosB expression in the nucleus accumbens （NAc） and the hippocam...Objective To investigate the effect of M5 muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it＇s effect on the FosB expression in the nucleus accumbens （NAc） and the hippocampus in the heroin sensitized rats. Methods Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides （AS-ONs） targeting M5 muscarinic receptor was transferred with the lipofectin. Results Microinjection of AS-ONs targeting M5 muscarinic receptor in the ventral tegmental area （VTA） blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus （DG） of the hippocam- pus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M5 muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M5 muscarinic receptor sense oligonucleotide （S-ONs） into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats. Conclusion Blocking M5 muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M5 muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.展开更多
AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant...AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg·d)], fluoxetine group [10 mg/(kg·d)] and control group (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P < 0.05). Compared to the control group, food intake was significantly suppressed from d 21 to 42 and weight loss was promoted from d 35 to 42 in the fluoxetine group (t = 2.52, P < 0.05). There was a significant difference in body weight of the mice after removal of tumors among the three groups. The body weight of mice was the heaviest (13.66 ± 1.55 g) in the mirtazapine group and the lightest (11.39 ± 1.45 g) in the fluoxetine group (F(2,12) = 11.43, P < 0.01). The behavioral test on d 7 showed that the horizontal and vertical activities were significantly increased in the mirtazapine group compared with the fluoxetine and control groups (F(2,18) = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was no significant difference in tumor vol- ume and tumor weight of the three groups. CONCLUSION: Mirtazapine and fluoxetine have no effect on the growth of pancreatic tumor. However, mirtazapine can significantly increase food intake and improve nutrition compared with fluoxetine in a pan- creatic cancer mouse model.展开更多
Stroke is a leading cause of death worldwide. Up to one thousand potential drugs or interventions have been developed to treat stroke, out of which;60 have gone on to clinical trials. However, none of them has been su...Stroke is a leading cause of death worldwide. Up to one thousand potential drugs or interventions have been developed to treat stroke, out of which;60 have gone on to clinical trials. However, none of them has been successful. New insights into the molecular and cellular mechanisms of ischemia-induced injury are needed for discovering new therapeutic targets. Recently, Drosophila has been used to uncover new hypoxia-related genes. In this study, we describe an efficient and reliable assay with a sophisticated apparatus for studying the effects of oxygen deprivation on flies. Using this assay, wild-type flies were exposed to an anoxic environment for varying lengths of time, then the cumulative death rate and mobility recovery were systematically analyzed. We found that anoxia for over one hour caused lethality. The cumulative death rate on day 5 after anoxia was linearly and positively correlatedwith the duration of anoxia, and reached 50% when the duration was 2.5 h–3 h. We also found that the mobility recovery in normoxia was slow, as the climbing ability remained largely unchanged 4 h–6 h after 2.5-h of anoxia.We suggest that 2.5 h–3 h of anoxia and 4 h–6 h of recovery before mobility analysis are appropriate for future use of the anoxia assay.展开更多
Dopamine D1 receptors（D1Rs） play a key role in cocaine addiction, and multiple protein kinases such as GRKs, PKA, and PKC are involved in their phosphorylation. Recently, we reported that protein kinase D1 phosphory...Dopamine D1 receptors（D1Rs） play a key role in cocaine addiction, and multiple protein kinases such as GRKs, PKA, and PKC are involved in their phosphorylation. Recently, we reported that protein kinase D1 phosphorylates the D1 R at S421 and promotes its membrane localization. Moreover, this phosphorylation of S421 is required for cocaineinduced behaviors in rats. In the present study, we generated transgenic mice over-expressing S421A-D1 R in the forebrain. These transgenic mice showed reduced phospho-D1R（S421） and its membrane localization, and reduced downstream ERK1/2 activation in the striatum. Importantly, acute and chronic cocaine-induced locomotor hyperactivity and conditioned place preference were significantly attenuated in these mice. These findings provide in vivo evidence for the critical role of S421 phosphorylation of the D1 R in its membrane localization and in cocaine-induced behaviors. Thus, S421 on the D1 R represents a potential pharmacotherapeutic target for cocaine addiction and other drug-abuse disorders.展开更多
The mass inoculation of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines to induce herd immunity is one of the most effective measures we can deploy in the fight against coronavirus disease 2019(COV...The mass inoculation of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines to induce herd immunity is one of the most effective measures we can deploy in the fight against coronavirus disease 2019(COVID-19).Pregnant women are prone to a higher risk of COVID-19,and maternal infection is a risk fac-tor for a range of neurological disorders leading to abnormal behavior in adulthood.However,there are limited clinical data to support whether vaccination or infection post-immunization in pregnant women can affect the behavioral cognition of fetuses in adulthood.In this study,human angiotensin-converting enzyme 2 pregnant mice(F0 generation)were immunized with CoronaVac and then infected with SARS-CoV-2.Subsequently,we analyzed the behavioral cognition of their adult offspring(F1 gen-eration)using the open-field test and Morris water maze test.The adult F1 generation did not exhibit any impairments in spontaneous locomotor activity or spatial refer-ence memory.展开更多
The use of medicinal plants in South Africa is cultural. Withania somnifera is one of the medicinal plants used to treat various ailments in the country. The plant species has been used by traditional medicine practit...The use of medicinal plants in South Africa is cultural. Withania somnifera is one of the medicinal plants used to treat various ailments in the country. The plant species has been used by traditional medicine practitioners to treat inflammation and painful conditions like rheumatism. It is also known to be used as a sedative and hypnotic drug. Despite the claims, there is no information in literature to corroborate the therapeutic success of Withania somnifera in the treatment of inflammation and insomnia. The study, therefore, investigated the anti-inflammatory and central nervous system depressant activities of the leaf aqueous extract of the plant species in mice and rats. Fresh leaves of W. somnifera were collected from Kirstenbosch Botanical Gardens, South Africa, authenticated by a taxonomist and a voucher specimen （UWC 005） deposited in the University＇s Herbarium. Leaf aqueous extract was prepared using standard extraction methods. The carrageenan-induced rat paw oedema test was used to determine the anti-inflammatory effects while pentobarbitone-induced sleep and locomotor activity tests were used to evaluate the sedative effect of the plant species. Phytochemical qualitative analysis, acute toxicity and HPLC studies of the plant species were also carried out using standard methods. The phytochemical qualitative analysis carried out on the dried powdered leaves of W. somnifera showed the presence of saponins, tannins and triterpene steroids. Leaf aqueous extract of IV. somnifera （100-200 mg/kg IP） significantly prolonged pentobarbitone （40 mg/kg, i.p.）-induced sleep in mice in a dose dependant manner. Diazepam （0.5 mg/kg, i.p.） significantly prolonged pentobarbitone （40 mg/kg, i.p.）-induced sleep in mice. The doses of 100 and 200 mg/kg （i.p.） of the plant species and 0.5 mg/kg （i.p.） of diazepam significantly reduced the locomotor activity of mice. Leaf aqueous extract of the plant species （50-200 mg/kg, i.p.） significantly reduced the oedema produced by carrageenan （1%） in rats over 90 min period of testing. Indomethacin （20 mg/kg, i.p.） significantly reduced carrageenan （1%）-induced oedema in rats over 120 min period of testing. The LDs0 value obtained for the leaf aqueous extract of the plant species following inter-peritoneal injection was 1,600 mg/kg while that following oral administration was probably over 4,000 mg/kg. The HPLC finger-print of the aqueous extract showed distinct peaks at the following retention times 2.977, 3.594, 4.154, 4.406, 4.660 and 15.267 min. The results obtained show that leaf aqueous extract of W. somnifera has both sedative and anti-inflammatory effects.展开更多
Cryptochrome 1(CRY1)functions as a light-responsive photoreceptor,which is crucial for circadian rhythms.The identity and function of CRY1 in Plutella xylostella remain unknown.In this study,cryl was cloned and identi...Cryptochrome 1(CRY1)functions as a light-responsive photoreceptor,which is crucial for circadian rhythms.The identity and function of CRY1 in Plutella xylostella remain unknown.In this study,cryl was cloned and identified in P xylostella.Then,a cry1-knockout strain(Cry1-KO)of P xylostella with a 2-bp deletion was established from the strain Geneva 88(G88)using the CRISPR/Cas9 technology.No daily temporal os-cillation of cryl was observed in G88 and Cry1-KO,and cryl mean daily transcription of Cry1-KO was lower than that of G88.Both G88 and Cry1-KO demonstrated rhythmic locomotion under the light/dark condition with Cryl-KO being more active than G88 in the daytime,whereas Cry1-KO completely lost rhythmicity under constant darkness.The developmental period of pre-adult of Cry1-KO was longer than that of G88;the lifespan of the Cry1-KO male adult was shorter than that of G88;the fecundity of Cry1-KO was lower than that of G88;and Cry1-KO showed lower intrinsic rate of increase(r),net repro-duction rate(Ro),finite increase rate(a),and longer mean generation time(T)than G88.Our results indicate that cryl is involved in the regulation of locomotor circadian rhythm and development in P xylostella,providing a potential target gene for controlling the pest and a basis for further investigation on circadian rhythms in lepidopterans.展开更多
The aim of this study was to investigate the toxic effects of aluminum （A1） on the model organism-Drosophila melanogaster. The study is especially concerned with the effects of aluminum on the fruit fly＇s developme...The aim of this study was to investigate the toxic effects of aluminum （A1） on the model organism-Drosophila melanogaster. The study is especially concerned with the effects of aluminum on the fruit fly＇s development, life span, and circadian rhythm in rest and activity. Flies were exposed to aluminum in concentrations from 40 to 280 mg/kg in rearing media or the flies were raised on control medium. Moreover, the life span of insects exposed to aluminum containing 40, 120, or 240 mg/kg of A1 in the medium, only during their larval development, during the whole life cycle and only in their adult life was tested. To check if aluminum and aging cause changes in D. melanogaster behavior, the locomotor activity of flies at different ages was recorded. Results showed that aluminum is toxic in concentrations above 160 mg/kg in the rearing medium. Depending on A1 concentration and time of exposure, the life span of the flies was shortened. At intermediate concentrations （120 mg/kg）, however, A1 had a stimulating effect on males increasing their life span and level of locomotor activity. At higher concentration the aluminum exposure increased or decreased the level of locomotor activity ofD. melanogaster depending on age of flies. In addition, in the oldest insects reared on aluminum supplemented media and in mid-aged flies reared on the highest concentration of A1 the daily rhythm of activity was disrupted.展开更多
N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone(6PPDQ)has attracted significant attention due to its highly acute lethality to sensitive salmonids.However,studies investigating the mechanisms underlying it...N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone(6PPDQ)has attracted significant attention due to its highly acute lethality to sensitive salmonids.However,studies investigating the mechanisms underlying its acute toxicity have been lacking.In this work,we demonstrated the sensitivity of rainbow trout to 6PPDQ-induced mortality.Moribund trout exhibited significantly higher brain concentrations of 6PPDQ compared to surviving trout.In an in vitro model using human brain microvascular endothelial cells,6PPDQ can penetrate the blood–brain barrier and enhance blood–brain barrier permeability without compromising cell viability.The time spent in the top of the tank increased with rising6PPDQ concentrations,as indicated by locomotion behavior tests.Furthermore,6PPDQ influenced neurotransmitter levels and m RNA expression of neurotransmission-related genes in the brain and exhibited strong binding affinity to target neurotransmission-related proteins using computational simulations.The integrated biomarker response value associated with neurotoxicity showed a positive linear correlation with trout mortality.These findings significantly contribute to filling the knowledge gap between neurological impairments and apical outcomes,including behavioral effects and mortality,induced by6PPDQ.展开更多
基金supported by the Manitoba Health Research Council Foundationthe Canadian Institutes of Health Research Foundationthe Health Science Centre Foundation
文摘Chronic long-term exposure to cuprizone causes severe brain demyelination in mice,which leads to changes in locomotion,working memory and anxiety.These findings suggest the importance of intact myelin for these behaviors.This study aimed to investigate the possible behavioral changes in mice with mild oligodendrocyte/myelin damage that parallels the white matter changes seen in the brains of patients with psychiatric disporders.We used the cuprizonetreated mouse model to test both tissue changes and behavioral functions（locomotor activity,anxiety status,and spatial working memory）.The results showed that mice given cuprizone in their diet for 7 days had no significant myelin breakdown as evaluated by immunohistochemical staining for myelin basic protein,while the number of mature oligodendrocytes was reduced.The number and length of Caspr protein clusters,a structural marker of the node of Ranvier,did not change.The locomotor activity of the cuprizonetreated mice increased whereas their anxiety levels were lower than in normal controls;spatial working memory,however,did not change.These results,for the first time,link emotion-related behavior with mild white matter damage in cuprizone-treated mice.
基金This research was funded by the authors with help from Fundacion para la Investigacion en Etologıa y Biodiversidad(FIEB),who funded a small portion of the hormonal analyzes.
文摘Human activities involving noise emission can affect wild animals.European mink was exposed to road noise and human voice playbacks to analyze how sound intensity level and duration of both noises altered the time that individuals were active and if their fecal cortisol metabolite(FCM)levels varied.A Hierarchical Analysis Cluster was performed to establish 2 mink groups with respect to both noise source type:short duration/low intensity(SL)and long duration/high intensity(LH).We performed general linear mixed models to evaluate the variation in locomotor activity duration(s)and FCM(nanogram per gram)levels,respectively.The results showed both road noise and human voices decreased locomotor activity duration in SL more sharply compared with LH,and human voices were the triggers that induced the most pronounced response to both exposure conditions.FCM(ng/g)levels increased in SL compared with LH during road noise while the opposite happened during human voices.Differences based on sex and age of individuals were observed.In conclusion,noise characteristics given by the sound type determined the variations in locomotor activity duration while noise exposure level determined the variations in FCM(ng/g)levels.Attention should be paid to noisy activities(e.g.,recreational activities for visitors in protected natural areas)and loud groups of people to conserve wildlife,especially noise sensitive species.
基金Startup Fund for scientific research,Fujian Medical University,Grant/Award Number:2020QH1039Joint Funds for the Innovation of Science and Technology,Fujian Province,Grant/Award Number:2020Y9114 and 2020Y9119。
文摘The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's cover.Then,the RJ25 adaptor relayed the running signal to the main control board.Finally,the main control board was connected to the USB port of the computer with the USB connection.Data were collected using the online-accessible,self-created software Magturning.Through Magturning,generated data were saved and exported in real time.Afterward,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light conditions.In conclusion,this new device can record circadian activity of rodents.Our device is appropriate for interdisciplinary investigations related to biological clock research.
基金Additional support for EIPC was provided by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454supported by the core funding from Temasek Life Sciences Laboratory,Singapore
文摘The three-dimensional organization of the genome plays a crucial role in regulating gene expression patterns in metazoans（Ong and Corces,2014）.The nuclear architectural proteins are known to facilitate the formation of topological domains within the genome through mediating inter-and intra-chromosomal interactions.In vertebrate,CCCTC-binding factor（CTCF）is the main architectural protein that mediates long-range chromosomal interactions among its DNA binding sites through a process that is stabilized by cohesin （Parelho et al., 2008; Wendt et al., 2008）.
文摘Valproic acid (VPA) is used in the treatment of epilepsy and behavioral disorders. However, the exposure to VPA during pregnancy increases the risk of having offspring with autism spectrum disorder (ASD). Reports indicate that men are more likely to suffer ASD than women who were exposed to VPA prenatally. Few studies have related the sex differences and behavioral changes in the ASD rat model. Our aim was to determinate whether male and female Wistar rats whose mothers were exposed to either VPA (600 mg/kg;animal model for ASD) or saline (0.9%) i.p. at 12.5 day of gestation, have different effects on immobility induce by clamping (IC), dorsal immobility (DI), catalepsy, locomotor activity, stereotypes, and analgesia (tail flick). For this purpose, we made four groups (n = 8). Group: A) saline male rats, B) saline female rats, C) VPA male rats and D) VPA female rats. At 35 (prepubertal age), 56 (postpubertal age) and 180 days, we tested the behaviors previously mentioned. Finding that VPA has the same effect on IC, catalepsy, and analgesia in male and female rats, the time of these tests was increased. However, VPA only has an effect on DI in males but not in female rats. On the contrary, there is hyperactivity and an increase of stereotypes in female but not in male rats. Thereby, VPA has an effect on the three immobility responses tested (IC, DI and catalepsy), locomotor activity and analgesia but in a differential way on DI, stereotypes and locomotor activity between male and female rats.
基金This study was supported by IDeA Networks of Biomedical Research Excellence(8P20GM103447,E.E.)the Oklahoma Center for the Advancement of Science and Technology(OCAST HR12-196,K.S.C.).
文摘Estrogens are well known to increase locomotor activity in laboratory rodents;however,the underlying mechanism remains unclear.We used voluntary wheel running by female rats as an index of locomotor behavior to investigate this issue.We first determined whether the estrogen-induced increase in locomotion was susceptible to inhibition by a physiological challenge,and next whether it was associated with dopaminergic activation in the central reward area,nucleus accumbens.Ovariectomized rats were given estradiol or the oil vehicle and housed in cages with or without running wheels.All rats were given regular rodent chow for 1 week,a sodium-deficient diet for the next week,and then were returned to a regular diet for another week.At the end of the last week,all rats were killed,brains were extracted and dopamine levels in the nucleus accumbens were measured.As expected,estradiol treatment increased distance run.Surprisingly,dietary sodium deprivation further increased running,but this appeared to be related to experience with wheel running,rather than to sodium deprivation,per se.Dopamine was greater in the nucleus accumbens of estradiol-treated rats that ran compared to all other groups.Thus,the estrogen-induced increase in locomotion is a robust phenomenon that is not inhibited by a body sodium challenge and is associated with elevated levels of dopamine in reward pathways.These findings raise the possibility that the estrogen-induced increase in locomotor activity,which occurs during a hormonal milieu conducive to reproduction,may reflect mate-seeking behavior and,thereby,maximize reproductive success.
基金V.S.was supported by a Leibniz-DAAD Postdoctoral Research Fellowship(no.91632699)while he is now supported by the Spanish Ministry of Science and Innovation with a “Juan de la Cierva Incorporacion”research fellowship(IJC2018-035389-1)he acknowledges the “Severo Ochoa Centre of Excellence”accreditation(CEX2019-000928-S).
文摘Consistent inter-individual differences in daily activity rhythms(i.e.,chronotypes)can have ecological consequences in determining access to food resources and avoidance of predators.The most common measure to characterize chronotypes in animals as well as humans is the onset of activity(i.e.,early or late chronotypes).However,daily activity rhythms may also differ in the relative amount of activity displayed at particular time periods.Moreover,chronotypes may also be linked to other consistent inter-individual differences in behavior(i.e.,personality),such as the propensity to take risks.Here,we used the signal crayfish Pacifastacus leniusculusto test the presence of chronotypes and risk-taking personality traits and a potential behavioral syndrome between these traits.We first exposed crayfish to 5 days of light-darkness to measure daily activity rhythms and then we applied a visual predator-simulating stimulus in 2 different contexts(neutral and food).Our results showed consistent(i.e.,across 5 days)inter-individual differences in the relative nocturnal activity displayed in the early and middle,but not in the late part of darkness hours.Moreover,while crayfish displayed inter-individual differences in risk-taking behavior,these were not found to be consistent across 2 contexts.Therefore,we were not able to formally test a behavioral syndrome between these 2 traits.In conclusion,our study provides the first evidence of chronotypes in the relative amount of activity displayed at particular time periods.This could be a valuable information for applied ecological aspects related to the signal crayfish,which is a major invasive species of freshwater ecosystems.
基金supported by the project CN_00000033 funded under the National Recovery and Resilience Plan(NRRP)Mission 4 Component 2 Investment 1.4-Call for tender No.3138 of 16 December 2021,rectified by Decree n.3175 of 18 December 2021 of the Italian Ministry of University and Research funded by the European UnionNextGenerationEU.
文摘The study of temperament and behavioral syndromes in insects is still in its early stage,and research conducted to date has mainly focused on locomotor activity and thanatosis.Dung beetles have been the subject of extensive behavioral studies;however,very few studies have addressed the expression of temperament.Those doing so only looked at subsocial and sexual horn dimorphic species,suggesting subsociality and/or sexual horn-dimorphism as possible facilitators of temperament expression.To test this assumption,we conducted a temperament study in a hornless,non-subsocial species,namely Geotrupes mutator(Marsham,1802).We set up laboratory tests to evaluate 3 behaviors(activity,thanatosis,and distress calls)through the measurement of 7 distinct behavioral traits(3 activity-,1 thanatosis-,and 3 call-related traits).We found high levels of individual repeatability in all activity-and thanatosis-related traits.We also identified behavioral differences between individuals,which may reflect differences in temperament.Statistical analyses revealed a negative correlation between activity and thanatosis.These results show that the temperament and behavioral syndromes related to activity and thanatosis may also be expressed in dung beetle species that are neither subsocial nor sexual horn dimorphic.By contrast,we only found one of 3 sound-related traits tested(frequency)to be clearly repeatable.Males and females presented a different structure of the stridulatory apparatus,suggesting that morphology may affect the frequency of sounds emitted.These results indicate that certain sound traits might not be good descriptors of individual temperament revealing the need for future research addressing the role of bioacoustics.
基金This work was supported by the National Nature Science Foundation of China （No.30470554）the National Basic Research Development Program of China（No.2003CB515404）.
文摘Objective To investigate the effect of M5 muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it＇s effect on the FosB expression in the nucleus accumbens （NAc） and the hippocampus in the heroin sensitized rats. Methods Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides （AS-ONs） targeting M5 muscarinic receptor was transferred with the lipofectin. Results Microinjection of AS-ONs targeting M5 muscarinic receptor in the ventral tegmental area （VTA） blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus （DG） of the hippocam- pus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M5 muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M5 muscarinic receptor sense oligonucleotide （S-ONs） into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats. Conclusion Blocking M5 muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M5 muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.
文摘AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg·d)], fluoxetine group [10 mg/(kg·d)] and control group (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P < 0.05). Compared to the control group, food intake was significantly suppressed from d 21 to 42 and weight loss was promoted from d 35 to 42 in the fluoxetine group (t = 2.52, P < 0.05). There was a significant difference in body weight of the mice after removal of tumors among the three groups. The body weight of mice was the heaviest (13.66 ± 1.55 g) in the mirtazapine group and the lightest (11.39 ± 1.45 g) in the fluoxetine group (F(2,12) = 11.43, P < 0.01). The behavioral test on d 7 showed that the horizontal and vertical activities were significantly increased in the mirtazapine group compared with the fluoxetine and control groups (F(2,18) = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was no significant difference in tumor vol- ume and tumor weight of the three groups. CONCLUSION: Mirtazapine and fluoxetine have no effect on the growth of pancreatic tumor. However, mirtazapine can significantly increase food intake and improve nutrition compared with fluoxetine in a pan- creatic cancer mouse model.
基金supported by the National Key Basic Research Program of China(2013CB530900)the National Natural Science Foundation of China(81371400 and 81771416)Shanghai Municipal Commission of Health and Family Planning(201740153)
文摘Stroke is a leading cause of death worldwide. Up to one thousand potential drugs or interventions have been developed to treat stroke, out of which;60 have gone on to clinical trials. However, none of them has been successful. New insights into the molecular and cellular mechanisms of ischemia-induced injury are needed for discovering new therapeutic targets. Recently, Drosophila has been used to uncover new hypoxia-related genes. In this study, we describe an efficient and reliable assay with a sophisticated apparatus for studying the effects of oxygen deprivation on flies. Using this assay, wild-type flies were exposed to an anoxic environment for varying lengths of time, then the cumulative death rate and mobility recovery were systematically analyzed. We found that anoxia for over one hour caused lethality. The cumulative death rate on day 5 after anoxia was linearly and positively correlatedwith the duration of anoxia, and reached 50% when the duration was 2.5 h–3 h. We also found that the mobility recovery in normoxia was slow, as the climbing ability remained largely unchanged 4 h–6 h after 2.5-h of anoxia.We suggest that 2.5 h–3 h of anoxia and 4 h–6 h of recovery before mobility analysis are appropriate for future use of the anoxia assay.
基金supported by grants from the National Natural Science Foundation of China (91332119,81161120497,30925015,30830044,31371143,30900582 and 81221002)the National Basic Research Development Program from the Ministry of Science and Technology of China (2014CB542204)
文摘Dopamine D1 receptors（D1Rs） play a key role in cocaine addiction, and multiple protein kinases such as GRKs, PKA, and PKC are involved in their phosphorylation. Recently, we reported that protein kinase D1 phosphorylates the D1 R at S421 and promotes its membrane localization. Moreover, this phosphorylation of S421 is required for cocaineinduced behaviors in rats. In the present study, we generated transgenic mice over-expressing S421A-D1 R in the forebrain. These transgenic mice showed reduced phospho-D1R（S421） and its membrane localization, and reduced downstream ERK1/2 activation in the striatum. Importantly, acute and chronic cocaine-induced locomotor hyperactivity and conditioned place preference were significantly attenuated in these mice. These findings provide in vivo evidence for the critical role of S421 phosphorylation of the D1 R in its membrane localization and in cocaine-induced behaviors. Thus, S421 on the D1 R represents a potential pharmacotherapeutic target for cocaine addiction and other drug-abuse disorders.
基金National Key Research and Development Project of China,Grant/Award Number:2020YFA0707600。
文摘The mass inoculation of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccines to induce herd immunity is one of the most effective measures we can deploy in the fight against coronavirus disease 2019(COVID-19).Pregnant women are prone to a higher risk of COVID-19,and maternal infection is a risk fac-tor for a range of neurological disorders leading to abnormal behavior in adulthood.However,there are limited clinical data to support whether vaccination or infection post-immunization in pregnant women can affect the behavioral cognition of fetuses in adulthood.In this study,human angiotensin-converting enzyme 2 pregnant mice(F0 generation)were immunized with CoronaVac and then infected with SARS-CoV-2.Subsequently,we analyzed the behavioral cognition of their adult offspring(F1 gen-eration)using the open-field test and Morris water maze test.The adult F1 generation did not exhibit any impairments in spontaneous locomotor activity or spatial refer-ence memory.
文摘The use of medicinal plants in South Africa is cultural. Withania somnifera is one of the medicinal plants used to treat various ailments in the country. The plant species has been used by traditional medicine practitioners to treat inflammation and painful conditions like rheumatism. It is also known to be used as a sedative and hypnotic drug. Despite the claims, there is no information in literature to corroborate the therapeutic success of Withania somnifera in the treatment of inflammation and insomnia. The study, therefore, investigated the anti-inflammatory and central nervous system depressant activities of the leaf aqueous extract of the plant species in mice and rats. Fresh leaves of W. somnifera were collected from Kirstenbosch Botanical Gardens, South Africa, authenticated by a taxonomist and a voucher specimen （UWC 005） deposited in the University＇s Herbarium. Leaf aqueous extract was prepared using standard extraction methods. The carrageenan-induced rat paw oedema test was used to determine the anti-inflammatory effects while pentobarbitone-induced sleep and locomotor activity tests were used to evaluate the sedative effect of the plant species. Phytochemical qualitative analysis, acute toxicity and HPLC studies of the plant species were also carried out using standard methods. The phytochemical qualitative analysis carried out on the dried powdered leaves of W. somnifera showed the presence of saponins, tannins and triterpene steroids. Leaf aqueous extract of IV. somnifera （100-200 mg/kg IP） significantly prolonged pentobarbitone （40 mg/kg, i.p.）-induced sleep in mice in a dose dependant manner. Diazepam （0.5 mg/kg, i.p.） significantly prolonged pentobarbitone （40 mg/kg, i.p.）-induced sleep in mice. The doses of 100 and 200 mg/kg （i.p.） of the plant species and 0.5 mg/kg （i.p.） of diazepam significantly reduced the locomotor activity of mice. Leaf aqueous extract of the plant species （50-200 mg/kg, i.p.） significantly reduced the oedema produced by carrageenan （1%） in rats over 90 min period of testing. Indomethacin （20 mg/kg, i.p.） significantly reduced carrageenan （1%）-induced oedema in rats over 120 min period of testing. The LDs0 value obtained for the leaf aqueous extract of the plant species following inter-peritoneal injection was 1,600 mg/kg while that following oral administration was probably over 4,000 mg/kg. The HPLC finger-print of the aqueous extract showed distinct peaks at the following retention times 2.977, 3.594, 4.154, 4.406, 4.660 and 15.267 min. The results obtained show that leaf aqueous extract of W. somnifera has both sedative and anti-inflammatory effects.
基金funded by the National Key R&D Program of China,grant number 2017YFD0200400the Special Key Project of Fujian Province,grant number 2018NZ01010013,and a fund of"111"program,grant numberKRA16001A.
文摘Cryptochrome 1(CRY1)functions as a light-responsive photoreceptor,which is crucial for circadian rhythms.The identity and function of CRY1 in Plutella xylostella remain unknown.In this study,cryl was cloned and identified in P xylostella.Then,a cry1-knockout strain(Cry1-KO)of P xylostella with a 2-bp deletion was established from the strain Geneva 88(G88)using the CRISPR/Cas9 technology.No daily temporal os-cillation of cryl was observed in G88 and Cry1-KO,and cryl mean daily transcription of Cry1-KO was lower than that of G88.Both G88 and Cry1-KO demonstrated rhythmic locomotion under the light/dark condition with Cryl-KO being more active than G88 in the daytime,whereas Cry1-KO completely lost rhythmicity under constant darkness.The developmental period of pre-adult of Cry1-KO was longer than that of G88;the lifespan of the Cry1-KO male adult was shorter than that of G88;the fecundity of Cry1-KO was lower than that of G88;and Cry1-KO showed lower intrinsic rate of increase(r),net repro-duction rate(Ro),finite increase rate(a),and longer mean generation time(T)than G88.Our results indicate that cryl is involved in the regulation of locomotor circadian rhythm and development in P xylostella,providing a potential target gene for controlling the pest and a basis for further investigation on circadian rhythms in lepidopterans.
文摘The aim of this study was to investigate the toxic effects of aluminum （A1） on the model organism-Drosophila melanogaster. The study is especially concerned with the effects of aluminum on the fruit fly＇s development, life span, and circadian rhythm in rest and activity. Flies were exposed to aluminum in concentrations from 40 to 280 mg/kg in rearing media or the flies were raised on control medium. Moreover, the life span of insects exposed to aluminum containing 40, 120, or 240 mg/kg of A1 in the medium, only during their larval development, during the whole life cycle and only in their adult life was tested. To check if aluminum and aging cause changes in D. melanogaster behavior, the locomotor activity of flies at different ages was recorded. Results showed that aluminum is toxic in concentrations above 160 mg/kg in the rearing medium. Depending on A1 concentration and time of exposure, the life span of the flies was shortened. At intermediate concentrations （120 mg/kg）, however, A1 had a stimulating effect on males increasing their life span and level of locomotor activity. At higher concentration the aluminum exposure increased or decreased the level of locomotor activity ofD. melanogaster depending on age of flies. In addition, in the oldest insects reared on aluminum supplemented media and in mid-aged flies reared on the highest concentration of A1 the daily rhythm of activity was disrupted.
基金supported by the National Natural Science Foundation of China(42177254)Science and Technology Planning Project of Guangdong Province(2020B1212030008)。
文摘N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone(6PPDQ)has attracted significant attention due to its highly acute lethality to sensitive salmonids.However,studies investigating the mechanisms underlying its acute toxicity have been lacking.In this work,we demonstrated the sensitivity of rainbow trout to 6PPDQ-induced mortality.Moribund trout exhibited significantly higher brain concentrations of 6PPDQ compared to surviving trout.In an in vitro model using human brain microvascular endothelial cells,6PPDQ can penetrate the blood–brain barrier and enhance blood–brain barrier permeability without compromising cell viability.The time spent in the top of the tank increased with rising6PPDQ concentrations,as indicated by locomotion behavior tests.Furthermore,6PPDQ influenced neurotransmitter levels and m RNA expression of neurotransmission-related genes in the brain and exhibited strong binding affinity to target neurotransmission-related proteins using computational simulations.The integrated biomarker response value associated with neurotoxicity showed a positive linear correlation with trout mortality.These findings significantly contribute to filling the knowledge gap between neurological impairments and apical outcomes,including behavioral effects and mortality,induced by6PPDQ.
