Neurophysiological, histological, and behavioral characterization of animal models of distraction spinal cord injury: a systematic review

Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.

Nicotine Addiction Models and Evaluation of Animal Behavior

Nicotine is one of the most widely concerning components of cigarette smoke.Long-term intake of nicotine can lead to nicotine dependence that affects higher brain functions,which may involve anxiety,learning and memory impairments,and abnormal decision-making.To facilitate analyzing the molecular mechanisms of nicotine dependence,it is common to establish rodent nicotine dependence models to better understand the physiological changes.This paper summarizes and evaluates the application of animal behavior evaluation experiments in nicotine-dependent animal models,in order to provide a reliable reference for researchers to establish rodent nicotine-dependent models for evaluation.

On the Precursory Abnormal Animal Behavior and Electromagnetic Effects for the Kobe Earthquake (M~6) on April 12, 2013

After the 2011 Tohoku earthquake (EQ), there have been numerous aftershocks in the eastern and Pacific Ocean of Japan, but EQs are still rare in the western part of Japan. In this situation a relatively large (magnitude (M) ~6) EQ happened on April 12 (UT), 2013 at a place close to the former 1995 Kobe EQ (M~7), so we have tried to find whether there existed any precursors to this EQ, especially abnormal animal behavior (milk yield of cows), observed at Kagawa, Shikoku, near the EQ epicenter. The milk yield of cows has been continuously monitored at Kagawa, and it is found that the milk yield exhibited an abnormal depletion about 10 days before the EQ. This behavior has been extensively compared with the former electromagnetic precursors (ULF radiation, ionos-pheric perturbation). This leads to the discussion on the sensory mechanism of unusual behavior of mild yield of cows, and it may be suggested that ULF radiation among different electromagnetic precursors is a mostly likely driver, at least, for this EQ.

The Marking Technology in Motion Capture for the Complex Locomotor Behavior of Flexible Small Animals(Gekko gecko)

Animals have evolved a variety of behavior patterns to adapt to the environment. Motion-capture technology is utilized to quantify and characterize locomotor behaviors to reveal the mechanisms of animal motion. In the capture of flexible, small animals with complex locomotor behaviors, the markers interfere with each other easily, and the motion forms(bending, twisting) of the moving parts are obviously different;thus, it is a great challenge to realize accurate quantitative characterization of complex locomotor behaviors. The correlation between the marker properties, including the size and space length, and the precision of the system are revealed in this paper, and the effects of diverse marker shapes on the capturing accuracy of the captured objects in different motion forms were tested. Results showed that the precision of system is significantly improved when the ratio of the space length to the diameter of the markers is larger than four;for the capture of the spatial twisting motion of the flexible object, the hexagon markers had the lowest spatial lost-marker rate relative to the circle, triangle, and square. Customized markers were used to capture the locomotor behavior of the gecko-inspired robot(rigid connection) and the gecko(flexible connection). The results showed that this marking technology can achieve high accuracy of motion capture for geckos(the average deviation was approximately 0.32 mm, and the average deviation’s variation rate was approximately 0.96%). In this paper, the marking technology for the motion capture of flexible, small animals with complex motion is proposed;it can effectively improve the system precision as well as the capture accuracy, and realize the quantitative characterization of the complex motion of flexible, small objects. It provides a reliable technical means to deeply study the evolution of the motion function of small animals and advance systematic research of motion-capture technology.

Electric Field Effects on Animals:Mechanism of Seismic Anomalous Animal Behaviors (SAABs)

Electric field effect on animals has been studied to investigate its relation with seismic anomalous animal behaviors(SAABs)in China.Freshwater eel,crucian carp,catfish,and soft-shelled turtle responded to the threshold electric field of 1-10 V/m,while duck,goose,cat,sheep,pig,dog,and chicken all responded to the ground electric field of about tens of V/m,depending on the species as well as on individuals.Most of the behaviors caused by electric field were similar to those reported as SAABs such as alignment,sudden movement,panic,and convulsion.The intensity of electric field due to a major earthquake would have been over these threshold values.Numerical estimation based on an electromagnetic model of a fault has been made to induce SAABs as electric shocks to pulsed electric fields in electro-physiology.The seismic electric signals(SES)intensity might be estimated from the observation of SAABs.

Use of 3D-printed animal models as a standard method to test avian behavioral responses toward nest intruders in the studies of avian brood parasitism

Living and/or non-living animal models are often used as stimuli to observe the behavioral responses of the target animals.In the past,parasites,predators,and harmless controls have been used to test host anti-parasitism defense behavior,and their taxidermy specimens have been widely used as a set of standard methods for the study of avian brood parasitism.In recent years,with the rapid development of 3D-printing technology,3D-printed bird models are expected to be applied as a standard method in the study of avian brood parasitism.To evaluate the use of 3D-printed models,this study tests the reaction of Oriental Reed Warbler(Acrocephalus orientalis)towards predators,parasites,or controls,and compares the reaction among different nest intruders and between taxidermy specimens and 3D-printed animal models.It was found that the Oriental Reed Warbler responded most aggressively to the parasite,followed by predator,and finally the control;the results were consistent between the reaction to taxidermy specimens and 3D-printed animal models,indicating that 3D-printed models could serve as a substitute for taxidermy specimens.We propose a series of advantages of using 3D-printed models and suggest them to be a standard method for widespread use in future studies of avian brood parasitism.

Pioneering Studies of Spatial Behavior in Animals: Ivane Beritashvili and Edward Tolman

Ivane S. Beritashvili’s doctrine of image-driven behavior was established in the late 1920s and finally extended in his books in English (1965;1971). It bears a strong resemblance to the concepts of purposive behavior and “cognitive maps” developed in parallel by Edward C. Tolman (1932;1948) and significantly anticipated respective modern concepts. John O’Keefe and his disciples May-Britt Moser and Edvard I. Moser received the Nobel Prize in 2014 for their discoveries of cells that constitute a navigation system in the brain. The latter fact brings us to the pioneers of the study of the spatial orientation of animals that figuratively speaking, provided the giant’s shoulders on which O’Keefe and the Mosers stood to receive their award. Beritashvili and Tolman upheld the holistic and goal-directed nature of spatial behavior. A major contribution of Beritashvili to the science of animal behavior was the demonstration of the universality of learning following a single presentation of an object vitally important to the animal: either a food object or a noxious signal. Beritashvili showed that such “image-driven” behavior has a strong spatial component, i.e., the image is projected into a definite point in space. Thus, he came to maintain that there is a class of behavior that is image-driven that does not require a repetition of associations. Tolman made several significant contributions to the field of experimental psychology. He thought of learning as developing from bits of knowledge and cognitions about the environment and how the organism relates to it. He examined the role that reinforcement plays in the way that rats learn their way through complex mazes. These experiments eventually led to the theory of latent learning which describes learning that occurs in the absence of an obvious reward. Tolman also strongly advocated the theory that rats learn the place where they have been rewarded rather than the particular movements required to get there. To a great extent, Tolman’s work determined the direction of American psychology in the 1930s-1950s. The contribution of Beritashvili and Tolman, thus, is the groundwork of modern studies of spatial cognitive processes in human and nonhuman animals.

Alignment silkworms as seismic animal anomalous behavior (SAAB) and electromagnetic model of a fault: a theory and laboratory experiment

Alignment of silkworms and fish, observed as seismic anomalous animal behavior (SAAB) prior to the Kobe earthquake, were duplicated in a laboratory by applying a pulsed electric field assuming SAAB as electrophysiological responses to the stimuli of seismic electric signals (SES). The animals became aligned perpendicularly to the field direction since their skeletal muscle had a higher resistivity perpendicular to the field direction than parallel to it. An electromagnetic model of a fault is proposed in which dipolar charges, ± q are generated due to the change of seismic stress, σ (t) . From a mathematical model,d q /d t=-α (d σ /d t) - q/ερ , where α is the charge generation constant like a piezoelectric coefficient, ε , the dielectric constant and ρ , the resistivity of bedrock granite. A fault having a length 2 a and a displacement or rock rupture time τ , during which the stress is changed, gives pulsed dipolar charge surface densities, +q(t, x) and -q(t, x+2a), or an apparent electric dipole moment of P(t)=2aQ(t)=2aAq(t)=αM 0[ερ/(τ-ερ)](e -t/τ -e -t/ερ ) using the earthquake moment M 0. The fault displacement, D , its initial velocity, D′ and the stress drop, Δ σ give τ=D/D′= (Δ σ/σ 0)(α/β) . The field intensity, F , and seismic current density at a fault zone, J were calculated as F=q/ε and J=F/ρ′ using ρ′ of water as to give J=0.1～1 A/m 2 sufficient to cause SAAB experimentally. The near field ultra low frequency (ULF) waves generated by P(t) give SES reciprocally proportional to the distance R .

ANIMAL BEHAVIORAL MODELS OF TINNITUS

The pathophysiology of tinnitus is poorly understood and treatments are often unsuccessful. A number of animal models have been developed in order to gain a better understanding of tinnitus. A great deal has been learned from these models re- garding the electrophysiological and neuroanatomical correlates of tinnitus following exposure to noise or ototoxic drugs. Re- liable behavioral data is important for determining whether such electrophysiological or neuroanatomical changes are indeed related to tinnitus. Of the many documented tinnitus animal behavioral paradigms, the acoustic startle reflex had been pro- posed as a simple method to identify the presence or absence of tinnitus. Several behavioral models based on conditioned re- sponse suppression paradigms have also been developed. In addition to determining the presence or absence of tinnitus, some of the behavioral paradigms have provided signs of the onset, frequency, and intensity of tinnitus in animals. Although none of these behavioral models have been proved to be a perfect model, these studies provide useful information on understanding the neural mechanisms underlying tinnitus.

Ventral Tegmental Area Neuronal Activity Correlates to Animals’ Behavioral Response to Chronic Methylphenidate Recorded from Adolescent SD Male Rats

Methylphenidate (MPD) is considered as the first-line pharmacotherapy to treat ADHD. More recently, MPD has also been used as a cognitive enhancement recreationally. Its therapeutic effects are not fully understood, nor are the long term effects of the drug on brain development. The ventral tegmental area (VTA) neuronal activity was recorded from freely behaving adolescent rats using a wireless recording system. Five groups were used: saline, 0.6, 2.5, 5.0 and 10.0 mg/kg MPD. The experiment lasted for 10 days. This study demonstrated that VTA neurons respond to MPD in a dose response characteristic and the same dose of MPD can cause both behavioral sensitization and behavioral tolerance. The neuronal unit activity was evaluated based on the animals’ behavioral activity following chronic MPD administration. The study showed that the animals’ behavioral response to different acute MPD of 0.6, 2.5 and 10.0 mg/kg doses responded in a dose response characteristics. Moreover, the same chronic dose of 0.6, 2.5, and 10.0 mg/kg MPD elicits in some animals’ behavioral sensitization and in some others behavioral tolerance. Therefore, the neuronal activity recorded from animals expressing behavioral sensitization was analyzed separately from the neuronal activity recorded from of behaviorally tolerant animals and it was found that the VTA units of the behaviorally sensitization animals responded significantly different to the drug than those VTA units recorded from animals expressing behavioral tolerance.

Ritalin Dose Response Effect on Medial Prefrontal Cortex and on Animal Behavior

The prefrontal cortex (PFC) is involved in complex planning, learning, memory, attention and integrates sensory information. It was reported that the PFC was dysfunctional in attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPD), a drug often prescribed for the treatment of ADHD, has potential for abuse and misuse. Most MPD studies were completed in adult subjects;however, most users were adolescents. The objective of this study was to investigate the acute and chronic dose response characteristics of MPD on PFC neuronal activity recorded in freely behaving adolescent rats. Four groups of animals were used: saline (control), 0.6, 2.5, and 10 mg/kg MPD. Acute MPD elicited a dose response increase in animals’ locomotor activity. Rechallenge with MPD at experimental day (ED10) when compared to the effect of MPD at ED1 showed no significant differences. When the animals were divided into two groups based on their individual responses to chronic MPD exposure, some animals expressed behavioral tolerance and some expressed behavioral sensitization. Electrophysiologically, a dose response characteristic for acute and chronic MPD exposure was observed. With increasing MPD doses, more PFC units responded by changing their firing rate. Moreover, the neuronal responses to chronic MPD recorded from animals expressing behavioral tolerance were significantly different compared to the neuronal population responses recorded from animals expressing behavioral sensitization. The majority of the PFC units recorded from animals expressing behavioral tolerance responded to MPD predominately by decreasing their firing rates, whereas PFC units recorded from behaviorally sensitized animals mainly showed an increase in their firing rates.

Role of 5-HT2A Receptors in Immunomodulation in Animal Models of Aggressive Behavior

Serotonin 5-HT2A receptors are playing an important role in the pathophysiology of aggressive behaviors and in the control of immune function. In the present study, we analyzed the effects of activation and blockade of 5-HT2A receptors with selective ligands on the immune response formation in animals with aggressive behaviors induced by genetic factors (rats selected for the increased aggressiveness toward human) or by chronic social stress (mice of the CBA/Lac strain engaged in 10 days of social confrontations). Activation of 5-HT2A receptors with DOI at 1.0 mg/kg reduced the immune response level both in aggressive rats and mice compared to the corresponding vehicle-treated groups, while DOI administration did not alter the immune reaction in nonaggressive animals. The blockade of 5-HT2A receptors with ketanserin at 1.0 mg/kg resulted in immunostimulation both in mice of the CBA strain not subjected to social stress (the controls) and in nonaggressive rats selected for elimination of aggressiveness. On the other hand, its administration to CBA mice demonstrating offensive aggression enhanced the immune reaction, while the same dose of ketanserin did not modify the immune response level in rats with genetic predisposition to the increased defensive aggression. Thus, our data suggest that the role of 5-HT2A receptors in immunomodulation depends on the specific type of aggression that may be taking into account in the treatment of some neuropsychiatric disorders with the antipsychotic drugs and antidepressants targeting 5-HT2A receptors.

Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

Finding biomarkers of experience in animals

At a time when there is a growing public interest in animal welfare,it is critical to have objective means to assess the way that an animal experiences a situation.Objectivity is critical to ensure appropriate animal welfare outcomes.Existing behavioural,physiological,and neurobiological indicators that are used to assess animal welfare can verify the absence of extremely negative outcomes.But welfare is more than an absence of negative outcomes and an appropriate indicator should reflect the full spectrum of experience of an animal,from negative to positive.In this review,we draw from the knowledge of human biomedical science to propose a list of candidate biological markers(biomarkers)that should reflect the experiential state of non-human animals.The proposed biomarkers can be classified on their main function as endocrine,oxidative stress,non-coding molecular,and thermobiological markers.We also discuss practical challenges that must be addressed before any of these biomarkers can become useful to assess the experience of an animal in real-life.

Clinical/Behavioral Monitoring of Rodents and Rabbits Undergoing Scientific Experiments

Background: We currently have international and national guidelines regarding the assessment and monitoring of clinical signs and humane endpoints in animals used in teaching and research, which make the performance of these activities mandatory for any experiment and professional working in this area. Assigning the severity of a research experiment is the result of an analysis of records of observations of the animal’s behavior, and clinical signs. The aim of this study was to describe the importance of carrying out a severity assessment associated with clinical and behavioral monitoring of rodents and rabbits during experimentation to maintain the welfare of these animals undergoing scientific research. Methods: The literature search was carried out using the following terms: “Monitoring”;“Humane endpoints”;“Animal welfare”, “Rodents”;“Rabbits”, and as connectors “and”;“or”, in the following databases: PubMed;LILACS/BIREME and SciELO. Results: A total of 987 articles were identified in the databases, and 20 of these studies were included in this review. Conclusions: Humane endpoint protocols and procedure severity tables are of the utmost importance, both from an ethical point and to refine the results of research conducted on laboratory animals. They should be drawn up jointly by the teams responsible for the project and the maintenance of the animals during the research period, and the data obtained should be published so that the scientific community can have access to it, helping to disseminate these practices, as well as helping to draw up new procedures. Monitoring and evaluating the welfare and clinical condition of animals undergoing scientific research procedures is the responsibility of the professors, researchers, veterinarians, and animal facility coordinators. The Ethics Committee on the Use of Animals must monitor all the activities conducted with the animals, by inspecting the experimental procedures and the physical environment of the laboratory animal facility where the animals are housed.

Cluster DetectionMethod of Endogenous Security Abnormal Attack Behavior in Air Traffic Control Network

In order to enhance the accuracy of Air Traffic Control(ATC)cybersecurity attack detection,in this paper,a new clustering detection method is designed for air traffic control network security attacks.The feature set for ATC cybersecurity attacks is constructed by setting the feature states,adding recursive features,and determining the feature criticality.The expected information gain and entropy of the feature data are computed to determine the information gain of the feature data and reduce the interference of similar feature data.An autoencoder is introduced into the AI(artificial intelligence)algorithm to encode and decode the characteristics of ATC network security attack behavior to reduce the dimensionality of the ATC network security attack behavior data.Based on the above processing,an unsupervised learning algorithm for clustering detection of ATC network security attacks is designed.First,determine the distance between the clustering clusters of ATC network security attack behavior characteristics,calculate the clustering threshold,and construct the initial clustering center.Then,the new average value of all feature objects in each cluster is recalculated as the new cluster center.Second,it traverses all objects in a cluster of ATC network security attack behavior feature data.Finally,the cluster detection of ATC network security attack behavior is completed by the computation of objective functions.The experiment took three groups of experimental attack behavior data sets as the test object,and took the detection rate,false detection rate and recall rate as the test indicators,and selected three similar methods for comparative test.The experimental results show that the detection rate of this method is about 98%,the false positive rate is below 1%,and the recall rate is above 97%.Research shows that this method can improve the detection performance of security attacks in air traffic control network.

Evidence for the Reliability and Validity of the Arabic Version of the Student Risk Screening Scale for Internalizing and Externalizing Behaviors (SRSS-IE)

School-based universal screening for behavioral/emotional risk is a necessary first step to providing services in an educational setting for students with emotional and behavioral disorders (EBDs). Psychometric properties are critical to making decisions about choosing a screening instrument. The purpose of the present study was to examine the psychometric properties of the student risk screening scale for internalizing and externalizing behaviors (SRSS-IE). Participants included 3145 students and their teachers. Item-level analyses of the current sample supported the retention of all items. The internal consistency of the SRSS items ranged from 0.83 to 0.85. Convergent validity between the SRSS-IE and a well-established screening tool, the strength and difficulties questionnaire (SDQ), was found for the total score (r = 0.70). Additionally, the results of this study demonstrate strong social validity, suggesting the SRSS-IE to be a useful and functional screening tool. We conclude that the SRSS-IE is a valid and reliable instrument for assessing the level of emotional and behavioral difficulties among elementary students.

Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment.Davunetide,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive protection.However,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood.In this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice.The neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral analysis.Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane.In adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine density.Furthermore,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane group.Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by sevoflurane.Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic proteins.Suppression of Wnt signaling was restored in the davunetide-treated group.Thus,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics.This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.

Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.