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1.
PeerJ ; 12: e17342, 2024.
Article En | MEDLINE | ID: mdl-38737745

Background: N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported. Objective: The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp). Methods: The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping. Results: Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring. Conclusions: This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.


Alprazolam , Drug Synergism , Sleep , Animals , Alprazolam/pharmacology , Alprazolam/administration & dosage , Mice , Male , Sleep/drug effects , Electroencephalography/drug effects , Proto-Oncogene Proteins c-fos/metabolism , Brain/drug effects , Brain/metabolism , Reflex, Righting/drug effects , Hypnotics and Sedatives/pharmacology , Hypnotics and Sedatives/administration & dosage
2.
BMC Anesthesiol ; 24(1): 167, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702608

The exact mechanisms and the neural circuits involved in anesthesia induced unconsciousness are still not fully understood. To elucidate them valid animal models are necessary. Since the most commonly used species in neuroscience are mice, we established a murine model for commonly used anesthetics/sedatives and evaluated the epidural electroencephalographic (EEG) patterns during slow anesthesia induction and emergence. Forty-four mice underwent surgery in which we inserted a central venous catheter and implanted nine intracranial electrodes above the prefrontal, motor, sensory, and visual cortex. After at least one week of recovery, mice were anesthetized either by inhalational sevoflurane or intravenous propofol, ketamine, or dexmedetomidine. We evaluated the loss and return of righting reflex (LORR/RORR) and recorded the electrocorticogram. For spectral analysis we focused on the prefrontal and visual cortex. In addition to analyzing the power spectral density at specific time points we evaluated the changes in the spectral power distribution longitudinally. The median time to LORR after start anesthesia ranged from 1080 [1st quartile: 960; 3rd quartile: 1080]s under sevoflurane anesthesia to 1541 [1455; 1890]s with ketamine. Around LORR sevoflurane as well as propofol induced a decrease in the theta/alpha band and an increase in the beta/gamma band. Dexmedetomidine infusion resulted in a shift towards lower frequencies with an increase in the delta range. Ketamine induced stronger activity in the higher frequencies. Our results showed substance-specific changes in EEG patterns during slow anesthesia induction. These patterns were partially identical to previous observations in humans, but also included significant differences, especially in the low frequencies. Our study emphasizes strengths and limitations of murine models in neuroscience and provides an important basis for future studies investigating complex neurophysiological mechanisms.


Anesthetics, Inhalation , Dexmedetomidine , Electroencephalography , Ketamine , Propofol , Sevoflurane , Animals , Mice , Ketamine/pharmacology , Ketamine/administration & dosage , Sevoflurane/pharmacology , Sevoflurane/administration & dosage , Dexmedetomidine/pharmacology , Electroencephalography/drug effects , Electroencephalography/methods , Propofol/pharmacology , Propofol/administration & dosage , Male , Anesthetics, Inhalation/pharmacology , Anesthetics, Inhalation/administration & dosage , Reflex, Righting/drug effects , Reflex, Righting/physiology , Mice, Inbred C57BL , Hypnotics and Sedatives/pharmacology , Hypnotics and Sedatives/administration & dosage , Anesthetics, Intravenous/pharmacology , Anesthetics, Intravenous/administration & dosage , Anesthesia/methods
3.
Behav Brain Res ; 468: 115025, 2024 Jun 25.
Article En | MEDLINE | ID: mdl-38710451

Prenatal stress (PS), in both humans and animals, presents a potential risk to the mother and her fetus throughout gestation. PS is always associated with physiological changes that alter embryonic development and predispose the individual to lifelong health problems, including susceptibility to mental illness. This study aims to identify the harmful effects of prenatal restraint stress (PRS), commonly employed to induce stress painlessly and without any lasting debilitation during gestation. This stress is applied to pregnant Swiss albino mice from E7.5 to delivery for three hours daily. Our results show that PS affects dams' weight gain during the gestational period; moreover, the PS dams prefer passive nursing, exhibit a lower percentage of licking and grooming, and impair other maternal behaviors, including nesting and pup retrieval. Concerning the offspring, this stress induces neurobehavioral impairments, including a significant increase in the time of recovery of the young stressed pups in the surface righting reflex, the latency to avoid the cliff in the cliff avoidance test, longer latencies to accomplish the task in negative geotaxis, and a lower score in swimming development. These alterations were accompanied by increased Malondialdehyde activity (MDA) at PND17 and 21 and downregulation of AchE activity in the whole brain of pups on postnatal days 7 and 9. These findings demonstrated that PS causes deleterious neurodevelopmental impairments that can alter various behaviors later in life.


Maternal Behavior , Oxidative Stress , Prenatal Exposure Delayed Effects , Restraint, Physical , Stress, Psychological , Animals , Pregnancy , Female , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/physiopathology , Mice , Stress, Psychological/metabolism , Stress, Psychological/physiopathology , Oxidative Stress/physiology , Maternal Behavior/physiology , Malondialdehyde/metabolism , Animals, Newborn , Brain/metabolism , Male , Acetylcholinesterase/metabolism , Behavior, Animal/physiology , Reflex, Righting/physiology , Avoidance Learning/physiology
4.
Neurosci Lett ; 832: 137815, 2024 May 29.
Article En | MEDLINE | ID: mdl-38723759

Recent studies have demonstrated that stress during the critical windows of development can evoke a cascade of neurological changes that can result in neuropsychiatric disorders later in life. In this study, we examined the effect of early-life inflammation on ethanol consumption in adolescent mice. C57BL/6J mice were assigned to either the control or Lipopolysaccharide (LPS) group on postnatal day 14 (P14). In the latter group, LPS at a dose of 50 µg/kg was injected intraperitoneally. The mice were weaned at P21, and behavior tests were performed at P45. Ethanol consumption was assessed using a two-bottle choice drinking paradigm. Anxiety-like behaviors were assessed by marble burying test (MBT), open field (OF), and elevated plus maze (EPM). Ethanol-induced loss of righting reflex (LORR), hypothermia and ethanol metabolism were assessed to evaluate ethanol intoxication. P14 LPS-injected adolescent male mice exhibited significantly increased ethanol preference and consumption, with a similar taste preference for saccharin and avoidance of quinine. The adolescent male mice showed increased anxiety-like behaviors in the OF and EPM tests, and an increased duration of LORR, without affecting the hypothermic effects of ethanol and ethanol metabolism. Interestingly, these behavioral changes were not obvious in female mice. In conclusion, our data indicate that early-life inflammation may be a risk factor for ethanol consumption in adolescents with greater changes observed in male mice. SIGNIFICANCE STATEMENT: Our study is the first preclinical model to report the enhancement effect of early-life inflammation on ethanol consumption in adolescent male mice and our findings provide a valuable mouse model to examine the neurobiological mechanisms mediating the long-lasting effects of early-life inflammation on alcohol use disorders vulnerability.


Alcohol Drinking , Anxiety , Ethanol , Inflammation , Lipopolysaccharides , Mice, Inbred C57BL , Animals , Male , Mice , Inflammation/chemically induced , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/toxicity , Ethanol/administration & dosage , Alcohol Drinking/psychology , Female , Anxiety/chemically induced , Behavior, Animal/drug effects , Reflex, Righting/drug effects
5.
Eur J Pharmacol ; 972: 176561, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38580182

Neuronal depression in the thalamus underlies anesthetic-induced loss of consciousness, while the precise sub-thalamus nuclei and molecular targets involved remain to be elucidated. The present study investigated the role of extrasynaptic GABAA receptors in the central medial thalamic nucleus (CM) in anesthesia induced by gaboxadol (THIP) and diazepam (DZP) in rats. Local lesion of the CM led to a decrease in the duration of loss of righting reflex induced by THIP and DZP. CM microinjection of THIP but not DZP induced anesthesia. The absence of righting reflex in THIP-treated rats was consistent with the increase of low frequency oscillations in the delta band in the medial prefrontal cortex. CM microinjection of GABAA receptor antagonist SR95531 significantly attenuated the anesthesia induced by systemically-administered THIP, but not DZP. Moreover, the rats with declined expression of GABAA receptor δ-subunit in the CM were less responsive to THIP or DZP. These findings explained a novel mechanism of THIP-induced loss of consciousness and highlighted the role of CM extrasynaptic GABAA receptors in mediating anesthesia.


Anesthesia , Isoxazoles , Receptors, GABA-A , Animals , Receptors, GABA-A/metabolism , Male , Rats , Isoxazoles/pharmacology , Diazepam/pharmacology , Rats, Sprague-Dawley , Mediodorsal Thalamic Nucleus/drug effects , Mediodorsal Thalamic Nucleus/metabolism , Mediodorsal Thalamic Nucleus/physiology , Reflex, Righting/drug effects , Synapses/drug effects , Synapses/metabolism , Thalamus/drug effects , Thalamus/metabolism
6.
Comp Med ; 74(1): 12-18, 2024 02 01.
Article En | MEDLINE | ID: mdl-38532260

General anesthesia induces a reversible loss of consciousness (LOC), a state that is characterized by the inability to feel pain. Identifying LOC in animals poses unique challenges, because the method most commonly used in humans, responding to questions, cannot be used in animals. For over a century, loss of righting reflex (LORR) has been used to assess LOC in animals. This is the only animal method that correlates directly with LOC in humans and has become the standard proxy measure used in research. However, the reporting of how LORR is assessed varies extensively. This systematic literature review examined the consistency and completeness of LORR methods used in rats and mice. The terms 'righting reflex,' 'anesthesia,' 'conscious,' 'rats,' 'mice,' and their derivatives were used to search 5 electronic databases. The abstracts of the 985 articles identified were screened for indications that the study assessed LORR in mice or rats. Full texts of selected articles were reviewed for LORR methodological completeness, with reported methods categorized by 1) animal placement method, 2) behavioral presence of righting reflex, 3) duration of LORR testing, 4) behavioral LORR, and 5) animal position for testing LORR. Only 22 papers reported on all 5 methodological categories. Of the 22 papers, 21 used unique LORR methodologies, with descriptions of LORR methods differing in at least one category as compared with all other studies. This variability indicates that even papers that included all 5 categories still had substantial differences in their methodological descriptions. These findings reveal substantial inconsistencies in LORR methodology and reporting in the biomedical literature likely compromising study replicability and data interpretation.


Anesthesia, General , Reflex , Humans , Rats , Mice , Animals , Reflex, Righting , Pain
7.
Sci Total Environ ; 918: 170552, 2024 Mar 25.
Article En | MEDLINE | ID: mdl-38309332

Anthropogenic noise has significantly increased due to human activities, posing a threat to the health and survival of marine organisms. However, current studies have often emphasized its effects on the physiological aspects of marine organisms, while ignored the relationship between the neuroendocrine system and behavior. This study aimed to evaluate the righting behavior and relevant physiological functions of the central nervous system (CNS) in sea slug (Onchidium reevesii) exposed to low-frequency noise and subsequent noise removal. The duration of the sea slugs' righting reflex increased with longer noise exposure time. The degree of neuronal cell damage and apoptosis were significantly increased and relevant gene expressions were affected (Glu, AChE, FMRFamide and CaMKII) (P < 0.05). After the removal of noise, the righting reflex speed gradually recovered, and the degree of neuronal cell damage, apoptosis and the expression levels of genes continued to decrease. Pearson correlation analysis showed that the righting time was positively correlated with CNS tissue and DNA damage, apoptosis rate, and negatively correlated with the expression levels of genes. Therefore, low-frequency noise exposure causes damage to the CNS of sea slugs, subsequently impairing their normal behavior. Sea slugs exhibited partial recovery within 384 h after removing noise. These findings provide valuable insights into the effects of low-frequency noise on the CNS and behavior of marine invertebrates.


Gastropoda , Animals , Humans , Reflex, Righting/physiology , Gastropoda/metabolism , Noise/adverse effects , Central Nervous System , Aquatic Organisms
8.
J Am Assoc Lab Anim Sci ; 63(2): 172-181, 2024 03 01.
Article En | MEDLINE | ID: mdl-38307499

The effects of commonly used injectable combinations of anesthetics such as ketamine and xylazine, with or without acepromazine, vary widely across individuals, have a shallow-dose response curve, and do not provide long-term analgesia. These drawbacks indicate the importance of continuing efforts to develop safe and effective injectable anesthetic combinations for mice. In this study, a series of experiments was designed to validate the use of dexmedetomidine and midazolam to provide chemical restraint for nonpainful procedures and the addition of buprenorphine or extended-release buprenorphine to reliably provide a surgical plane of anesthesia in C57BL/6J mice. Loss of consciousness was defined as the loss of the righting reflex (LORR); a surgical plane of anesthesia was defined as the LORR and loss of pedal withdrawal after application of a 300 g noxious stimulus to a hind paw. The combination of intraperitoneal 0.25 mg/kg dexmedetomidine and 6 mg/kg midazolam produced LORR, sufficient for nonpainful or noninvasive procedures, without achieving a surgical plane in 19 of 20 mice tested. With the addition of subcutaneous 0.1 mg/kg buprenorphine or 1 mg/kg buprenorphine-ER, 29 of 30 mice achieved a surgical plane of anesthesia. The safety and efficacy of the regimen was then tested by successfully performing a laparotomy in 6 mice. No deaths occurred in any trial, and, when administered 1 mg/kg atipamezole IP, all mice recovered their righting reflex within 11 min. The anesthetic regimen developed in this study is safe, is reversible, and includes analgesics that previous studies have shown provide analgesia beyond the immediate postsurgical period. Buprenorphine-ER can be safely substituted for buprenorphine for longer-lasting analgesia.


Buprenorphine , Dexmedetomidine , Mice, Inbred C57BL , Midazolam , Reflex, Righting , Animals , Dexmedetomidine/administration & dosage , Dexmedetomidine/pharmacology , Buprenorphine/pharmacology , Buprenorphine/administration & dosage , Midazolam/administration & dosage , Midazolam/pharmacology , Mice , Male , Reflex, Righting/drug effects , Delayed-Action Preparations , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/pharmacology , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/pharmacology , Anesthesia/veterinary , Anesthetics, Combined/administration & dosage
9.
J Am Assoc Lab Anim Sci ; 62(6): 553-558, 2023 Nov 11.
Article En | MEDLINE | ID: mdl-37770194

Exposure to CO2 gas is a common rodent euthanasia method. CO2 activates nociceptors in rats and is painful to humans at concentrations equal to or greater than 32.5% The concentration of CO2 at which rodents become unconsciousness is inadequately defined. We used loss of righting reflex (LORR) to identify the concentration at which CO2 caused loss of consciousness in C57Bl/6, CD1 and 129P3J mice (16 females and 16 males per strain). We used a custom built, rotating, motorized cylinder to determine LORR as CO2 concentrations were increased. Two LORR assessment methods were used: 1) a 1-Paw assessment in which the righting reflex was considered to be present if one or more paws contacted the cylinder after rotation into dorsal recumbency and 2) a 4-Paw assessment in which the righting reflex was considered to be present only if all 4 paws contacted the cylinder. LORR test data were analyzed with Probit regression and dose response curves were plotted. 1-Paw EC95 values (CO2 concentration at which LORR occurred for 95% of the population) were: C57Bl/6; 30.7%, CD1; 26.2%, 129P3J; 20.1%. The EC95 for C57Bl/6 was significantly higher than that of the 129P3J mice, with no significant differences between other strains. Four-Paw EC95 values were: C57Bl/6; 22.8%, CD1; 25.3%, 129P3J; 20.1%. Values for 129P3J mice were significantly lower than those of CD1 mice), with no significant difference between other strains. The EC95 varied significantly between 1-Paw and 4-Paw methods only for C57Bl/6 mice. These results suggest a potential for nociception and pain to occur in some individuals of some mouse strains during CO2 euthanasia.


Carbon Dioxide , Animals , Female , Male , Mice , Mice, Inbred C57BL , Pain/veterinary , Reflex , Reflex, Righting/physiology , Unconsciousness
10.
Mar Pollut Bull ; 193: 115250, 2023 Aug.
Article En | MEDLINE | ID: mdl-37421913

Offshore renewables are expanding, yet more information is required to understand their possible impacts on the environment. Little is known about the effects of Electromagnetic Fields (EMF) from subsea power cables on marine life. This study simulated an EMF of 500 µT, as modelled for an export cable over a rocky shore, where the industry standard cable burial would not be possible. Righting reflex, refractive index of haemolymph/coelomic fluid, and total haemocyte/coelomocyte counts were measured for four coastal invertebrates (Asterias rubens, Echinus esculentus, Necora puber, and Littorina littorea). No significant differences were found in either behavioural or physiological responses. This was the first study to investigate EMF exposure on righting reflex, and the first ever EMF study on edible sea urchins and periwinkles, and only one of a couple for common starfish and velvet crabs. It therefore, provides valuable data for environmental impact assessments, marine spatial planning, and commercial fisheries.


Brachyura , Gastropoda , Animals , Electromagnetic Fields , Reflex, Righting , Renewable Energy , Environment
11.
Sci Rep ; 13(1): 6138, 2023 04 15.
Article En | MEDLINE | ID: mdl-37061548

We study how falling hoverflies use sensory cues to trigger appropriate roll righting behavior. Before being released in a free fall, flies were placed upside-down with their legs contacting the substrate. The prior leg proprioceptive information about their initial orientation sufficed for the flies to right themselves properly. However, flies also use visual and antennal cues to recover faster and disambiguate sensory conflicts. Surprisingly, in one of the experimental conditions tested, hoverflies flew upside-down while still actively flapping their wings. In all the other conditions, flies were able to right themselves using two roll dynamics: fast ([Formula: see text]50ms) and slow ([Formula: see text]110ms) in the presence of consistent and conflicting cues, respectively. These findings suggest that a nonlinear sensory integration of the three types of sensory cues occurred. A ring attractor model was developed and discussed to account for this cue integration process.


Diptera , Proprioception , Animals , Reflex, Righting , Cues
12.
J Nat Med ; 77(3): 561-571, 2023 Jun.
Article En | MEDLINE | ID: mdl-37115471

Nerve inflammation is linked to the development of various neurological disorders. This study aimed to examine whether Glycyrrhizae Radix effectively influences the duration of the pentobarbital-induced loss of righting reflex, which may increase in a mouse model of lipopolysaccharide (LPS)-induced nerve inflammation and diazepam-induced γ-aminobutyric acid receptor hypersensitivity. Furthermore, we examined the anti-inflammatory effects of Glycyrrhizae Radix extract on LPS-stimulated BV2 microglial cells, in vitro. Treatment with Glycyrrhizae Radix significantly decreased the duration of pentobarbital-induced loss of righting reflex in the mouse model. Furthermore, treatment with Glycyrrhizae Radix significantly attenuated the LPS-induced increases in interleukin-1ß, interleukin-6, and tumor necrosis factor-alpha at the mRNA level, and it significantly reduced the number of ionized calcium-binding adapter molecule-1-positive cells in the hippocampal dentate gyrus 24 h after LPS treatment. Treatment with Glycyrrhizae Radix also suppressed the release of nitric oxide, interleukin-1ß, interleukin-6, and tumor necrosis factor protein in culture supernatants of LPS-stimulated BV2 cells. In addition, glycyrrhizic acid and liquiritin, active ingredients of Glycyrrhizae Radix extract, reduced the duration of pentobarbital-induced loss of righting reflex. These findings suggest that Glycyrrhizae Radix, as well as its active ingredients, glycyrrhizic acid and liquiritin, may be effective therapeutic agents for the treatment of nerve inflammation-induced neurological disorders.


Drugs, Chinese Herbal , Glycyrrhiza , Mice , Animals , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Glycyrrhizic Acid/pharmacology , Pentobarbital/pharmacology , Pentobarbital/therapeutic use , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Diazepam/therapeutic use , Reflex, Righting , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Hippocampus/metabolism , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Drugs, Chinese Herbal/pharmacology
13.
J Vestib Res ; 33(2): 115-125, 2023.
Article En | MEDLINE | ID: mdl-36776086

BACKGROUND: Video head impulse test (vHIT) and videonystagmography (VNG) provide significant benefits in evaluating benign paroxysmal positional vertigo (BPPV) and determining the semicircular canal localization of the otoconia. OBJECTIVE: This study aimed to investigate the relationship between vestibular-ocular reflex (VOR) gains measured via vHIT and the slow-phase velocity (SPV) of nystagmus in patients with the posterior semicircular canal (PSCC)-BPPV. METHODS: Sixty-two patients were included in this study and divided into the study (n = 32, patients with isolated PSCC-BPPV) and control (n = 30, age- and sex-matched healthy individuals) groups. While VOR gains were measured with vHIT in both groups and compared between groups, the SPV values of nystagmus observed during the Dix-Hallpike maneuver in the study group were recorded using VNG and compared with the VOR gains of the study group. RESULTS: There were significant differences in posterior canal VOR gains between the study and control groups (p < 0.001 and p < 0.01, respectively). Although the affected PSCC had decreased VOR gains versus the control group, it was still within the normal range. However, there was no significant relationship between the VOR gains of the affected PSCC and the SPV of the nystagmus. CONCLUSIONS: vHIT can help detect semicircular canal dysfunction in patients with PSCC-BPPV. The SPV values of nystagmus on VNG during the Dix-Hallpike maneuver do not correlate with the level of VOR gain.


Benign Paroxysmal Positional Vertigo , Nystagmus, Pathologic , Humans , Benign Paroxysmal Positional Vertigo/diagnosis , Prospective Studies , Semicircular Canals , Nystagmus, Pathologic/diagnosis , Reflex, Righting
14.
Food Chem Toxicol ; 171: 113540, 2023 Jan.
Article En | MEDLINE | ID: mdl-36460224

Raspberry ketone (RK; [4-(4-hydroxyphenyl)-2-butanone]) is a synthetic flavoring agent and dietary supplement for weight control. This study investigated the metabolic signature of oral doses of RK that prevent weight gain or promote loss of righting reflex (LORR) in C57Bl/6J mice. Daily RK 200 mg/kg prevented high-fat diet (HFD; 45% Kcal fat) fed weight gain (∼8% reduction) over 35 days. RNA-seq of inguinal white adipose tissue (WAT) performed in males revealed 12 differentially expressed genes. Apelin (Apln) and potassium voltage-gated channel subfamily C member (Kcnc3) expression were elevated with HFD and normalized with RK dosing, which was confirmed by qPCR. Acute RK 640 mg/kg produced a LORR with a <5 min onset with a >30 min duration. Acute RK 200 mg/kg increased gene expression of Apln, Kcnc3, and nuclear factor erythroid 2-related factor 2 (Nrf2), but reduced acetyl-COA carboxylase (Acc1) and NAD(P)H quinone dehydrogenase 1 (Nqo1) in inguinal WAT. Acute RK 640 mg/kg elevated interleukin 6 (Il 6) and heme oxygenase 1 (Hmox1) expression, but reduced Nrf2 in inguinal and epididymal WAT. Our findings suggest that RK has a dose-dependent metabolic signature in WAT associated with either weight control or LORR.


NF-E2-Related Factor 2 , Weight Gain , Mice , Male , Animals , NF-E2-Related Factor 2/metabolism , Reflex, Righting , Adipose Tissue, White/metabolism , Diet, High-Fat , Mice, Inbred C57BL , Shaw Potassium Channels/metabolism
15.
Environ Pollut ; 309: 119699, 2022 Sep 15.
Article En | MEDLINE | ID: mdl-35787424

Anthropogenic aquatic noise is recognised as an environmental pollutant with the potential to negatively affect marine organisms. Seismic surveys, used to explore subseafloor oil reserves, are a common source of aquatic noise that have garnered attention due to their intense low frequency inputs and their frequent spatial overlap with coastal fisheries. Commercially important Southern Rock Lobster (Jasus edwardsii) adults have previously shown sensitivity to signals from a single seismic air gun. Here, the sensitivity of J. edwardsii juveniles and puerulus to the signals of a full-scale seismic survey were evaluated to determine if early developmental stages were affected similarly to adults, and the range of impact. To quantify impact, lobster mortality rates, dorsoventral righting reflex and progression through moult cycle were evaluated following exposure. Exposure did not result in mortality in either developmental stage, however, air gun signals caused righting impairment to at least 500 m in lobsters sampled immediately following exposure, as had previously been reported in adults with corresponding sensory system damage following exposure. Impairment resulting from close range (0 m) exposure appeared to be persistent, as previously reported in adults, whereas juveniles exposed at a more distant range (500 m) showed recovery, indicating that exposure at a range of 500 m may not cause lasting impairment to righting. Intermoult duration was (time between moults) significantly increased in juveniles exposed at 0 m from the source, indicating the potential for slowed development, growth, and physiological stress. These results demonstrate that exposure to seismic air gun signals have the potential to negatively impact early life history stages of Southern Rock Lobsters. The similarity of both the impacts and the sound exposure levels observed here compared to previous exposure using a single air gun offer validation for the approach, which opens the potential for accessible field-based experimental work into the impact of seismic surveys on marine invertebrates.


Palinuridae , Animals , Larva/physiology , Noise , Palinuridae/physiology , Reflex, Righting , Seafood
16.
Science ; 376(6594): 754-758, 2022 05 13.
Article En | MEDLINE | ID: mdl-35549420

Insects have evolved sophisticated reflexes to right themselves in mid-air. Their recovery mechanisms involve complex interactions among the physical senses, muscles, body, and wings, and they must obey the laws of flight. We sought to understand the key mechanisms involved in dragonfly righting reflexes and to develop physics-based models for understanding the control strategies of flight maneuvers. Using kinematic analyses, physical modeling, and three-dimensional flight simulations, we found that a dragonfly uses left-right wing pitch asymmetry to roll its body 180 degrees to recover from falling upside down in ~200 milliseconds. Experiments of dragonflies with blocked vision further revealed that this rolling maneuver is initiated by their ocelli and compound eyes. These results suggest a pathway from the dragonfly's visual system to the muscles regulating wing pitch that underly the recovery. The methods developed here offer quantitative tools for inferring insects' internal actions from their acrobatics, and are applicable to a broad class of natural and robotic flying systems.


Flight, Animal , Odonata , Reflex, Righting , Animals , Flight, Animal/physiology , Odonata/physiology , Wings, Animal/physiology
17.
J Nat Med ; 76(3): 634-644, 2022 Jun.
Article En | MEDLINE | ID: mdl-35257304

Neuroinflammation is associated with the development of hypoactive delirium, which results in poor clinical outcomes. Drugs effective against hypoactive sur have not yet been established. Yokukansan has an anti-neuroinflammatory effect, making it potentially effective against hypoactive delirium. This study aimed to examine the effect of Yokukansan on the pentobarbital-induced loss of righting reflex duration extended with lipopolysaccharide (LPS)-induced neuroinflammation and diazepam-induced gamma-aminobutyric acid receptor stimulation in a mouse model. The active ingredients in Yokukansan and its anti-neuroinflammatory effect on the hippocampus were also investigated. Furthermore, we examined the in vitro anti-inflammatory effects of Yokukansan on LPS-stimulated BV2 cells, a murine microglial cell line. Findings revealed that treatment with Yokukansan significantly decreased the duration of pentobarbital-induced loss of righting reflex by attenuating the LPS-induced increase in interleukin-6 and tumor necrosis factor-alpha levels in the hippocampus. Moreover, treatment with Yokukansan significantly decreased the number of ionized calcium-binding adapter molecule-1-positive cells in the hippocampal dentate gyrus after 24 h of LPS administration. In addition, glycyrrhizic acid, an active ingredient in Yokukansan, partially decreased the duration of pentobarbital-induced loss of righting reflex. Treatment with Yokukansan also suppressed the expression of inducible nitric oxide, interleukin-6, and tumor necrosis factor mRNA in LPS-stimulated BV2 cells. Thus, these findings suggest that Yokukansan and glycyrrhizic acid may be effective therapeutic agents for treating neuroinflammation-induced hypoactive delirium.


Delirium , Lipopolysaccharides , Animals , Delirium/metabolism , Diazepam/metabolism , Diazepam/pharmacology , Diazepam/therapeutic use , Drugs, Chinese Herbal , Glycyrrhizic Acid/pharmacology , Hippocampus , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Mice , NF-kappa B/metabolism , Neuroinflammatory Diseases , Pentobarbital/metabolism , Pentobarbital/pharmacology , Pentobarbital/therapeutic use , Reflex, Righting , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
18.
J Vestib Res ; 32(2): 193-203, 2022.
Article En | MEDLINE | ID: mdl-34151876

BACKGROUND: Self-motion misperception has been observed in vestibular patients during asymmetric body oscillations. This misperception is correlated with the patient's vestibular discomfort. OBJECTIVE: To investigate whether or not self-motion misperception persists in post-ictal patients with Ménière's disease (MD). METHODS: Twenty-eight MD patients were investigated while in the post-ictal interval. Self-motion perception was studied by examining the displacement of a memorized visual target after sequences of opposite directed fast-slow asymmetric whole body rotations in the dark. The difference in target representation was analyzed and correlated with the Dizziness Handicap Inventory (DHI) score. The vestibulo-ocular reflex (VOR) and clinical tests for ocular reflex were also evaluated. RESULTS: All MD patients showed a noticeable difference in target representation after asymmetric rotation depending on the direction of the fast/slow rotations. This side difference suggests disruption of motion perception. The DHI score was correlated with the amount of motion misperception. In contrast, VOR and clinical trials were altered in only half of these patients. CONCLUSIONS: Asymmetric rotation reveals disruption of self-motion perception in MD patients during the post-ictal interval, even in the absence of ocular reflex impairment. Motion misperception may cause persistent vestibular discomfort in these patients.


Meniere Disease , Motion Perception , Vestibule, Labyrinth , Humans , Meniere Disease/diagnosis , Reflex, Righting , Reflex, Vestibulo-Ocular
19.
Laterality ; 27(2): 129-171, 2022 Mar.
Article En | MEDLINE | ID: mdl-34488564

This paper reports a series of tests for fore- and hind-limb preferences used by cane toads, Rhinella marina, to assist returning to the righted position after being overturned. We confirm the strong and significant right-handedness reported in this species, which under certain conditions exceeded 90% right-hand preference at the group level. Toads were tested under a variety of conditions including horizontal and inclined surfaces, with and without the opportunity for the forelimbs to grasp a support, in order to assess the effects of different vestibular and proprioceptive input on the strength and direction of fore- and hind-limb preferences. A range of behavioural strategies indicated learning effects; however, the strength or direction of limb preferences did not increase significantly with experience, even in toads retested multiple times. Comparisons with the mammalian condition for limb preferences are discussed with relevance to practice effects and established limb preferences, and to effects associated with arousal or stress. In contrast to the expectation that handedness in toads represents intentional or voluntary preferences, the presence of lateralized central pattern generators in the toads is postulated to explain the different forms of lateralization revealed by our tests.


Functional Laterality , Mammals , Animals , Bufo marinus/physiology , Reflex, Righting
20.
Article En | MEDLINE | ID: mdl-34664104

Many animals, including insects, need to solve the problem of self-righting if inverted and substrate is one understudied factor that could affect righting ability. In this study we ask the questions, how does Halyomorpha halys self-right and does variation in substrate affect self-righting? To address our questions we used four substrates with different features and filmed H. halys righting response on each substrate (n = 22 individuals). We also used two synced cameras to film the most common righting method and quantified its kinematics. Self-righting metrics did vary depending on substrate in terms of diversity of righting methods used, duration of the successful righting event, number of fails per attempt, and stance width. We also determined that the symmetrical forward flip is the most common method used by H. halys. In the forward flip H. halys creates a tripod of support using the hindlegs and the tip of the abdomen to elevate the anterior portion of the body off the substrate and pitch forward onto its feet. In addition to demonstrating that substrate can impact self-righting and quantifying the symmetrical forward flip, we also provide a foundation for future explorations of sensory feedback and adaptive motor control using H. halys.


Biomechanical Phenomena/physiology , Reflex, Righting/physiology , Touch Perception/physiology , Animals , Heteroptera , Surface Properties
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