Behavioral Alterations Research Articles

Role of the telomeric factor TRF2 in post-hypoxic brain damages

The neuronal excitotoxicity that follows reoxygenation after a hypoxic period may contribute to epilepsy, Alzheimer's disease, Parkinson's disease and various disorders that are related to inadequate supplement of oxygen in neurons. Therefore, counteracting the deleterious effects of post-hypoxic stress is an interesting strategy to treat a large spectrum of neurodegenerative diseases. Here, we show that the expression of the key telomere protecting protein Trf2 decreases in the brain of mice submitted to a post-hypoxic stress. Moreover, downregulating the expression of Terf2 in hippocampal neural cells of unchallenged mice triggers an excitotoxicity-like phenotype including glutamate overexpression and behavioral alterations while overexpressing Terf2 in hippocampal neural cells of mice subjected to a post-hypoxic treatment prevents brain damages. Moreover, Terf2 overexpression in culture neurons counteracts the oxidative stress triggered by glutamate. Finally, we provide evidence that the effect of Terf2 downregulation on excitotoxicity involves Sirt3 repression leading to mitochondrial dysfunction. We propose that increasing the level of Terf2 expression is a potential strategy to reduce post-hypoxic stress damages.

Alzheimer's Disease Neuropathological Change in Aged Non-Primate Mammals.

Human brain aging is characterized by the production and deposition of β-amyloid (Aβ) in the form of senile plaques and cerebral amyloid angiopathy and the intracellular accumulation of hyper-phosphorylated tau (Hp-tau) to form neurofibrillary tangles (NFTs) and dystrophic neurites of senile plaques. The process progresses for years and eventually manifests as cognitive impairment and dementia in a subgroup of aged individuals. Aβ is produced and deposited first in the neocortex in most aged mammals, including humans; it is usually not accompanied by altered behavior and cognitive impairment. Hp-tau is less frequent than Aβ pathology, and NFTs are rare in most mammals. In contrast, NFTs are familiar from middle age onward in humans; NFTs first appear in the paleocortex and selected brain stem nuclei. NFTs precede for decades or years Aβ deposition and correlate with dementia in about 5% of individuals at the age of 65 and 25% at the age of 85. Based on these comparative data, (a) Aβ deposition is the most common Alzheimer's disease neuropathological change (ADNC) in the brain of aged mammals; (b) Hp-tau is less common, and NFTs are rare in most aged mammals; however, NFTs are the principal cytoskeletal pathology in aged humans; (c) NFT in aged humans starts in selected nuclei of the brain stem and paleocortical brain regions progressing to the most parts of the neocortex and other regions of the telencephalon; (d) human brain aging is unique among mammalian species due to the early appearance and dramatic progression of NFTs from middle age onward, matching with cognitive impairment and dementia in advanced cases; (e) neither mammalian nor human brain aging supports the concept of the amyloid cascade hypothesis.

Induction of torpor in response to a common chronic food restriction paradigm: implications for behavioural research using mice

Background Many behavioural, pharmacological, and metabolic studies in mice require fasting, yet the possibility of fasting-induced torpor affecting data is rarely considered. Torpor is a state characterised by depressed metabolism and profound alterations in physiology and behaviour. In this study, we aimed to determine whether a chronic food restriction paradigm, common in behavioural studies, was sufficient to induce torpor in mice. Methods Mice were food restricted to ~85-90% of their bodyweight, as is typically done, and monitored using continuous thermal imaging. Results We observed that body temperature significantly decreased over days of food restriction, and it was significantly related to the drop in bodyweight (r2=0.8989, p<0.0001). All mice reliably entered torpor daily from day 8 of food restriction which coincided with bodyweight stabilisation at ~85%. We found a strong positive relationship between the magnitude of the decrease of bodyweight and the proportion of mice entering torpor each day (r2=0.8715, p<0.0001). Conclusions Overall, we found that torpor is readily induced in response to food restriction. Considering that hunger is frequently used as a motivational drive in behavioural tasks, it is likely that torpor occurrence is common in such studies, while remaining undetected and unaccounted for. Due to the profound effect of torpor on physiology, it is possible that torpor induction may be confounding subsequent data and represents an important source of variation. We recommend that body temperature is always monitored noninvasively in studies where food restriction is employed, to determine when torpor is occurring, and that torpor history is appropriately controlled for within and across experimental groups.

In-vitro and in-vivo studies of two-drug cocktail therapy targeting chemobrain via the Nrf2/NF-κB signaling pathway.

Today, we critically need alternative therapeutic options for chemotherapy-induced cognitive impairment (CICI), often known as chemo brain. Mitochondrial dysfunction and oxidative stress are two of the primary processes that contribute to the development of chemobrain. Therefore, the purpose of this study was to investigate how CoQ10 and berberine shield neurons from chemotherapy-induced damage in in-vitro studies and memory loss in vivo studies. For the in-vitro investigation, we employed SH-SY5Y cell lines, and for the in-vivo study, we used female Swiss albino mice divided into seven different groups. Data from in-vitro studies revealed that treatment with coenzyme Q10 (CoQ10) and berberine improved chemotherapy-induced toxicity by reducing mitochondrial and total cellular ROS, as well as apoptosis-elicited markers (caspase 3 and 9). CoQ10 and berberine therapy inhibited the nuclear translocation of NF-κB and, consequently, the subsequent expressions of NLRP3 and IL-1β, implying the prevention of inflammasome formation. Furthermore, CoQ10 and berberine therapy boosted Nrf2 levels. This is a regulator for cellular resistance to oxidants. The in vivo results showed that treatment with CoQ10 (40mg/kg) and berberine (200mg/kg) improved the behavioral alterations induced by CAF (40/4/25mg/kg) in both the Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests. Furthermore, biochemical and molecular evidence revealed the antioxidant, mitochondrial restorative, and anti-inflammatory potential of CoQ10 (40mg/kg) and berberine (200mg/kg) against CAF (40/4/25mg/kg) subjected mice. In addition, the histological analysis using H&E staining and transmission electron microscopy (for mitochondrial morphology) showed that mice treated with the cocktails had an increased number of healthy neurons with intact mitochondria and a reduced presence of autophagic vacuoles in the hippocampal region of the brain. These findings back up our theory about this novel cocktail method for CAF-induced cognitive impairment.

Proximity driven plastid-nucleus relationships are facilitated by tandem plastid-ER dynamics.

Peri-nuclear clustering (PNC) of chloroplasts has largely been described in senescent and pathogen- or ROS- stressed cells. Stromules, tubular plastid extensions are also observed under similar conditions. Coincident observations of PNC and stromules associate the two phenomena in facilitating retrograde signaling between chloroplasts and the nucleus. However, PNC incidence in non-stressed cells under normal growth and developmental conditions, when stromules are usually not observed, remains unclear. Using transgenic Arabidopsis expressing different organelle-targeted fluorescent proteins we show that PNC is a dynamic subcellular phenomenon that continues in the absence of light and is not dependent on stromule formation. PNC is facilitated by tandem plastid-ER dynamics created through membrane contact sites between the two organelles. While PNC increases upon ER-membrane expansion, some plastids may remain in the peri-nuclear region due to their localization in ER-lined nuclear indentions. Moreover, some PNC plastids may sporadically extend stromules into ER-lined nuclear grooves. Our findings strongly suggest that PNC is not an exclusive response to stress caused by pathogens, high light or exogenous-H2O2 treatment and does not require stromule formation. However, morphological and behavioural alterations in ER and concomitant changes in tandem, plastid-ER dynamics play a major role in facilitating the phenomenon.

Actively Viewing the Audio-Visual Media: An Eye-Controlled Application for Experience and Learning in Traditional Chinese Painting Exhibitions

Traditional unidirectional communication through audio-visual media, such as video and slide, is a universal method of vividly narrating artifacts in museums. This traditional method is evolving with the integration of new technologies to engage visitors, enhancing their experience and learning. In recent years, eye-controlled interaction has been used to enrich traditional exhibitions, especially of ancient paintings. This article presents an eye-controlled application for actively viewing the audio-visual media of a traditional Chinese painting. Users can trigger animations and audio narrations by focusing their gaze on specific areas of the screen. To evaluate the value of experience and learning in integrating audio-visual media with eye-controlled interaction, we compared Eye-Controlled Application with the two baseline conditions (Video and Slide) through a comparison experiment (N = 40) in terms of user experience, learning outcome, cognitive load, intrinsic motivation, and visual behavior. The findings indicated the positive effects of Eye-Controlled Application on experience and learning, especially understanding. Users had stronger intrinsic motivation using Eye-Controlled Application, which contributed to positive learning outcomes. We found that Eye-Controlled Application changed visual behavior by increasing the proportion of gaze patterns and decreasing the proportion of movement patterns and scan patterns. The alteration in visual behavior primarily stemmed from the eye-controlled interaction, which directed the user’s focus toward specific areas, thereby guiding their attention to the necessary content. Additionally, the qualitative results suggested that each of the three conditions had its advantages and disadvantages. Importantly, the condition with Eye-Controlled Application carried potential risks of distraction, reduced efficiency, and increased burden. This study contributes to the potential of eye-controlled interaction for enhancing visitors’ experience and learning, providing new insights into the development of interactive audio-visual media within museums.

Revealing the Freezing-Induced Alteration in Microplastic Behavior and Its Implication for the Microplastics Released from Seasonal Ice.

Ice can serve as a significant temporary repository and conveyance mechanism for microplastics (MPs). MPs present in the water column can become entrapped within developing ice formations, subsequently being sequestered and transported by ice floes. With changing temperatures, MPs stored in ice can be released back into the environment, while freezing conditions can alter the properties of MPs, ultimately affecting the fate of MPs in the environment. Freezing of MPs in freshwater ice results in the aggregation of MP particles due to physical compression, leading to an increase in particle size once the MPs are released from the ice. The freezing-induced aggregation enhances buoyancy effects, accelerating the settling/rising velocity of MPs in water. Additionally, freezing can lead to enhanced surface wetting alterations, thus improving the dispersion of hydrophobic MPs. The presence of salt in the water can mitigate the effect of freezing on MPs due to the formation of a brine network within the ice structure, which reduces the pressure on MPs entrapped by ice. In cold regions, numerous MPs undergo freezing and thawing, re-entering the water column.

Extraction, Phytochemical profile, and neuroprotective activity of Phyllanthus emblica fruit extract against sodium valproate-induced postnatal autism in BALB/c mice

The aim of the present study was to evaluate the effect of the ethyl acetate fraction of amla (EAFA) extract on valproic acid (VPA)-induced postnatal autism in BALB/c mice. Our study revealed that mice treated with VPA on postnatal day 14 (PND14) showed significant abnormal behaviours such as social interaction, social affiliation, anxiety, and motor coordination compared to the control group, while EAFA extract treatment (100 mg/kg) ameliorated these symptoms. Our study highlights the protective effect of EAFA extract on improving behavioural alterations, significantly restoring anti-oxidative enzymes such as GST and GR, and reducing MDA and NO levels. Furthermore, the EAFA-treated group significantly lowered the proinflammatory markers (IL-1β and TNF-α) and the expression of up-regulated 5-HT1D, 5-HT2A, and D2 receptor proteins. Based on histopathological studies, the percentage of neuronal injury in the EAFA-treated group as well as cellular structural changes were reduced using SEM analysis. In conclusion, the present study suggests that treatment with EAFA extract ameliorates VPA-induced autism due to its anti-oxidant and neuroprotective activity.

Effects of Prenatal Dexamethasone Treatment and Post-Weaning Moderate Fructose Intake on Synaptic Plasticity and Behavior in Adult Male Wistar Rat Offspring.

Early-life glucocorticoid overexposure induces diverse neurodevelopmental outcomes regarding stress reactivity and cognition. Increased fructose consumption has also been associated with alterations in cognitive capacity and behavior. The present study investigated the effects of prenatal dexamethasone exposure on synaptic plasticity, locomotion, anxiety, and recognition memory in adult male Wistar rat offspring, and whether these effects are potentiated by postnatal fructose consumption. Pregnant female rats were treated with dexamethasone during late gestation and male offspring were supplemented with a moderate dose of fructose. Recognition memory, locomotion, and anxiety-like behavior were assessed using a novel object recognition test, open-field test, and elevated plus maze, respectively. Hippocampal synaptic plasticity was estimated by the levels of growth-associated protein 43 (GAP-43), synaptophysin, postsynaptic density protein 95, calcium/calmodulin-dependent kinase IIα, and their activating phosphorylations. Additionally, protein levels of the glucocorticoid receptor (GR) and its transcriptionally active phosphorylated form were evaluated. Prenatal dexamethasone treatment induced an anxiolytic-like effect, stimulation of exploratory behavior, and novelty preference associated with an increase in GR and GAP-43 protein levels in the hippocampus. Fructose overconsumption after weaning did not modify the effects of prenatal glucocorticoid exposure. Applied prenatal dexamethasone treatment may induce changes in reactions to novel situations in male Wistar rats.

Reversible leukoencephalopathy with seizures: a case of severe high-altitude cerebral edema

BackgroundAcute high-altitude illness (AHAI) refers to a series of syndromes including acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). Among these, HACE is a severe and potentially life-threatening condition that can occur when individuals ascend to high altitudes. It is often characterized by ataxia, confusion, and altered mental status. Without appropriate treatment, HACE can rapidly progress to coma, but seizures are infrequent in occurrence.Case presentationHere, we report a severe HACE patient with coma and status epilepticus. The patient is a 23-year-old male who was visiting Lhasa for the first time. He initially experienced headaches and dizziness on the first day, and then he was found in coma with limb convulsions on the next day. Immediate medical attention was sought, and brain CT and MRI scans showed reversible white matter lesions, especially in the corpus callosum and subcortical white matter. Although the lesions disappeared on T1 and T2 sequences, microbleeds were observed on the SWI sequence. After treatment with tracheal intubation, glucocorticoids and hyperbaric oxygen, the cerebral edema has resolved and the clinical symptoms improved, the patient has no seizures anymore.ConclusionsHACE typically follows AMS and poses a significant risk to life. Clinical manifestations mainly include ataxia, alterations of behavior, and impaired consciousness, with severe cases progressing to coma. Seizures, though rarely observed, may occur. Imaging shows reversible white matter lesions, with microbleeds being a significant and persistent imaging marker over time. Administration of glucocorticoids plays a crucial role in treatment. Despite experiencing seizures, this patient did not experienced any further episodes once his condition improved.

Advancements in Novel Mechano-Rheological Probes for Studying Glassy Dynamics in Nanoconfined Thin Polymer Films.

The nanoconfinement effects of glassy polymer thin films on their thermal and mechanical properties have been investigated thoroughly, especially with an emphasis on its altered glass transition behavior compared to bulk polymer, which has been known for almost three decades. While research in this direction is still evolving, reaching new heights to unravel the underlying physics of phenomena observed in confined thin polymer films, we have a much clearer picture now. This, in turn, has promoted their application in miniaturized and functional applications. To extract the full potential of such confined films, starting from their fabrication, function, and various applications, we must realize the necessity to have an understanding and availability of robust characterization protocols that specifically target thin film thermo-mechanical stability. Being nanometer-sized in thickness, often atop a solid substrate, direct mechanical testing on such films becomes extremely challenging and often encounters serious complexity from the dominating effect of the substrate. In this review, we have compiled together a few important novel and promising techniques for mechano-rheological characterization of glassy polymer thin films. The conceptual background involved in each technique, constitutive equations, methodology, and current status of research are touched upon following a pedagogical tutorial approach. Further, we discussed each technique's success and limitations, carefully covering the puzzling or contradicting observations reported within the broad nexus of glass transition temperature-viscosity-modulus-molecular mobility (including diffusion and relaxation).

Exploring the role of environmental enrichment and early life adversity on emotional development

Early life adversity has been linked with a higher probability of developing behavioral impairments and environmental manipulation is a strategy that may reduce the negative effects of exposure to adversity in early life. Here, we focused on exploring the influence of environmental enrichment (EE) as a protective factor in the context of early life adversity. We hypothesized that 24 hours of maternal deprivation (MD), in the second week of life, could induce anxiety-like behavior alterations and that exposure to EE could induce resilience to these behaviors due to alterations in the serotonergic system. Male Wistar rats were exposed to MD, on postnatal days 11 and 13, and to EE, after weaning. In adulthood, we performed a series of behavioral tests for fear, anxiety, and locomotor activity. We also measured the levels of serotonin in the amygdala and dorsal raphe nucleus. Our results revealed that MD does not impact fear behavior or the levels of serotonin, while EE decreases locomotor activity in a novel environment and enhances exploration in the predator odor test. EE also decreases serotonin in the amygdala and increases its turnover rate levels. Our findings provide insights into the critical timeframe during which stress exposure impacts the development and confirm that exposure to EE has an independent and protective effect for anxiety-like behaviors later in life.

Standard diet and animal source influence hippocampal spatial reference learning and memory in congenic C57BL/6J mice.

Assessing learning and memory has become critical to evaluate brain function in health, aging or neurological disease. The hippocampus is crucially involved in these processes as illustrated by H.M.'s remarkable case and by the well-established early symptoms of Alzheimer's disease. Numerous studies have reported the impact of gut microbiota on hippocampal structure and function using pro-, pre- and antibiotics, diet manipulations, germ-free conditions or fecal transfer. However, most diet manipulations have relied on Western diet paradigms (high fat, high energy, high carbohydrates). Here, we compared the impact of two standard diets, 5K52 and 2918 (6% fat, 18% protein, 3.1kcal/g), and how they influenced hippocampal learning and memory in adult 6-month-old congenic C57BL/6J mice from two sources. Using a hippocampal-dependent task, we found that 5K52-fed mice performed consistently better than 2918-fed animals in the Barnes circular maze. These behavioral differences were accompanied with marked changes in microbiota, which correlated with spatial memory retention performance. We next tested whether 2918-induced alterations in behavior and microbiome could be rescued by 5K52 diet for 3 months. Changing the 2918 diet to 5K52 diet mid-life improved spatial learning and memory in mice. Shotgun sequencing and principal component analyses revealed significant differences at both phylum and species levels. Multivariate analyses identified Akkermansia muciniphila or Bacteroidales bacterium M11 and Faecalibaculum rodentium as the strongest correlates to spatial memory retention in mice depending on the animal source. In both settings, the observed behavioral differences only affected hippocampal-dependent performance as mice fed with either diet did similarly well on the non-spatial variant of the Y-maze. In summary, these findings demonstrate the diverging effects of seemingly equivalent standard diets on hippocampal memory. Based on these results, we strongly recommend the mandatory inclusion of the diet and source of animals used in rodent behavioral studies.

Cellular and Molecular Biology of Mitochondria in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by enduring airflow limitation and chronic inflammation. Growing evidence highlights mitochondrial dysfunction as a critical factor in COPD development and progression. This review explores the cellular and molecular biology of mitochondria in COPD, focusing on structural and functional changes, including alterations in mitochondrial shape, behavior, and respiratory chain complexes. We discuss the impact on cellular signaling pathways, apoptosis, and cellular aging. Therapeutic strategies targeting mitochondrial dysfunction, such as antioxidants and mitochondrial biogenesis inducers, are examined for their potential to manage COPD. Additionally, we consider the role of mitochondrial biomarkers in diagnosis, evaluating disease progression, and monitoring treatment efficacy. Understanding the interplay between mitochondrial biology and COPD is crucial for developing targeted therapies to slow disease progression and improve patient outcomes. Despite advances, further research is needed to fully elucidate mitochondrial dysfunction mechanisms, discover new biomarkers, and develop targeted therapies, aiming for comprehensive disease management that preserves lung function and enhances the quality of life for COPD patients.

Longitudinal sex-specific impacts of high-fat diet on dopaminergic dysregulation and behavior from periadolescence to late adulthood

ABSTRACT Objectives: Obesity is recognized for its adverse impact on brain health and related behaviors; however, the specific longitudinal effects of a high-fat diet (HFD) from juvenile stages of development through late adulthood remain poorly understood, particularly sex-specific outcomes. This study aimed to determine how prolonged exposure to HFD, commencing during periadolescence, would differentially predispose male and female mice to an elevated risk of dopaminergic dysregulation and associated behavioral deficits. Methods: One-month-old C57BL/6J male and female mice were subjected to either a control diet or an HFD for 5 and 9 months. Muscle strength, motor skills, sensorimotor integration, and anxiety-like behaviors were assessed at the end of the 5th and 8th months. Key dopaminergic molecules, including dopamine (DA), dopamine receptor D2 (DRD2), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2), were quantified at the end of the 5th or 9th months. Results: Behaviorally, male mice exposed to HFD exhibited more pronounced alterations in sensorimotor integration, anxiety-like behavior, and muscle strength after the 5th month of dietary exposure. In contrast, female mice displayed most behavioral differences after the 8th month of HFD exposure. Physiologically, there were notable sex-specific variations in the dopaminergic pathway response to HFD. Male mice exposed to HFD exhibited elevated tissue levels of VMAT2 and DRD2, whereas female mice showed reduced levels of DRD2 and DAT compared to control groups. Discussion: These findings indicate a general trend of altered time course susceptibility in male mice to chronic HFD consumption compared to their female counterparts, with male mice impacted earlier than females.

Fish 3D Locomotion app: a user-friendly computer application package for automatic data calculation and endpoint extraction for novel tank behavior in fish.

This paper introduces the Fish 3D Locomotion app (F3LA), a Python-based, Graphical User Interface (GUI)-equipped tool designed to automate behavioral endpoint extraction in zebrafish locomotion assays. Building on our previous work, which utilized a specialized aquatic tank with a mirror and a single camera for fish movement tracking in three dimensions, F3LA significantly enhances data processing efficiency. Its accuracy was tested by reanalyzing and comprehensively comparing the calculated data with the previously published data from prior publications. From the comparison results, 90% of endpoints showed a similar statistical difference result. These minor differences were due to the different starting points for the dataset and updated calculation formulas that are implemented in F3LA. In addition, shoaling area or shoaling volume calculations are also included in F3LA as a new feature that can serve as sensitive indicators of social cohesion, group dynamics, or stress responses, offering insights into neuropsychological conditions or the effects of pharmacological interventions. Furthermore, F3LA offers a marked improvement over manual operations, being at least five times faster, while maintaining consistent accuracy as it reduces human-induced errors, ensuring a higher degree of reliability in the results. Finally, the potency of F3LA was tested to evaluate the toxicities of 14 rare earth elements (REEs) to the adult zebrafish behaviors. Based on the results, our findings suggested that each tested REE altered fish behaviors in different patterns and magnitudes to each other. However, among the tested light rare earth elements (LREEs), neodymium was demonstrated to cause more relatively severe behavior alterations than other LREEs, indicated by the statistically higher value of entropy (0.2695 ± 0.04977 (mean with a standard deviation)) than the control group (0.2352 ± 0.05896). Meanwhile, in terms of heavy rare earth elements (HREEs), erbium seemed to lead to more distinct behavior toxicities than other HREEs, which was shown by the statistically lower level of fractal dimension (2.022 ± 0.3412) than the untreated group (2.255 ± 0.1661). Taken together, F3LA's development marks a significant advance in high-throughput toxicological and pharmacological assessments in zebrafish, leveraging three-dimensional locomotion data for a more comprehensive analysis of fish behavior performance, providing a significant contribution to research in various fields.

Sex-specific GABAergic microcircuits that switch vulnerability into resilience to stress and reverse the effects of chronic stress exposure.

Clinical and preclinical studies have identified somatostatin (SST)-positive interneurons as key elements that regulate the vulnerability to stress-related psychiatric disorders. Conversely, disinhibition of SST neurons in mice results in resilience to the behavioral effects of chronic stress. Here we established a low-dose chronic chemogenetic protocol to map these changes in positively and negatively motivated behaviors to specific brain regions. AAV-hM3Dq mediated chronic activation of SST neurons in the prelimbic cortex (PLC) had antidepressant drug-like effects on anxiety- and anhedonia-related motivated behaviors in male but not female mice. Analogous manipulation of the ventral hippocampus (vHPC) had such effects in female but not male mice. Moreover, activation of SST neurons in the PLC of male and the vHPC of female mice resulted in stress resilience. Activation of SST neurons in the PLC reversed prior chronic stress-induced defects in motivated behavior in males but was ineffective in females. Conversely, activation of SST neurons in the vHPC reversed chronic stress-induced behavioral alterations in females but not males. Quantitation of c-Fos+ and FosB+ neurons in chronic stress-exposed mice revealed that chronic activation of SST neurons leads to a paradoxical increase in pyramidal cell activity. Collectively, these data demonstrate that GABAergic microcircuits driven by dendrite targeting interneurons enable sex- and brain-region-specific neural plasticity that promotes stress resilience and reverses stress-induced anxiety- and anhedonia-like motivated behavior. Our studies provide a mechanistic rationale for antidepressant efficacy of dendrite-targeting, low-potency GABAA receptor agonists, independent of sex and despite striking sex differences in the relevant brain substrates.

Epicatechin as a promising agent against arsenic-induced neurobehavioral toxicity in NMRI mice: behavioral and biochemical alterations.

Epicatechin (Epi) is one of the most abundant flavonoids present in different fruits and tea leaves. Emerging research illuminates the promising potential of catechins to serve as a shield against the damaging effects of arsenic (As) exposure in diverse organs.This study sought to discern whether Epi exhibits a therapeutic efficacy against arsenic-induced neurotoxicity in a murine model.The Naval Medical Research Institute (NMRI) mice were randomly partitioned into six distinct groups, which included a control group receiving normal saline, a group receiving a daily oral dose of arsenic (10mg/kg) for 5weeks, groups receiving As (10mg/kg/day) orally for 5weeks along with different doses of Epi (25-100mg/kg) orally for the last 2weeks, and a group receiving Epi (100mg/kg) orally for 2weeks. To assess the potential effects of Epi, neurobehavioral tests, various parameters of oxidative stress, and inflammation were evaluated.The findings of this investigation revealed that As-induced neurobehavioral toxicity was associated with a notable surge in lipid peroxidation and nitric oxide (NO) concentration, accompanied by a reduction in the levels of antioxidant markers. As heightened pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) levels were observed alongside amplified nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. However, treatment with Epi reversed these effects.On the whole, these findings indicate that Epi may hold promise therapeutic efficacy on As-induced neurotoxicity by improving antioxidant status and mitigating oxidative stress and inflammation. Nevertheless, further research is imperative to comprehensively grasp the potential protective effects of Epi in this particular context.

Exploring the risk of microplastics to pollinators: focusing on honey bees.

The rapid increase in global plastic production and usage has led to global environmental contamination, with microplastics (MPs) emerging as a significant concern. Pollinators provide a crucial ecological service, while bee populations have been declining in recent years, and MPs have been recognized as a new risk factor contributing to their losses. Despite the pervasive distribution and persistence of MPs, understanding their risks to honey bees remains a critical knowledge gap. This review summarizes recent studies that investigate the toxicity of MPs on honey bee health from different perspectives. The findings revealed diverse and material-/size-/dosage-dependent outcomes, emphasizing the need for comprehensive assessments in the follow-up studies. MPs have been detected in honey and in bees' organs (e.g., gut and brain), posing potential threats to bee fitness, including altered behavior, cognitive abilities, compromised immunity, and dysfunction of the gut microbiota. It should be noticed that despite several laboratory studies suggesting the aforementioned adverse effects of MPs, field/semi-field experiments are still warranted. The synergistic toxicity of MPs with other environmental contaminants (pesticides, antibiotics, fungicides, heavy metals, etc.) still requires further investigation. Our review highlights the critical need to understand the relationships between MPs, pollinators, and the ecosystem to mitigate potential risks and ensure the sustainability of vital services provided by honey bees.

Gene therapy for Dravet syndrome: promises and impact on disease trigger and secondary modifications

Dravet syndrome is a severe epileptic syndrome that begins during the first year of life of otherwise healthy babies. Over the years, the seizure burden changes, and pathology evolves in strong association with behavioral alterations, including cognitive delay and autistic traits. Initially, this aspect was considered a direct consequence of epilepsy severity, and DS was defined as an epileptic encephalopathy. Increasing evidence suggests that these two aspects of the disease, epilepsy and behavioral impairment, might not be so strictly connected. DS is mostly caused by heterozygous loss-of-function mutations in the SCN1A gene, which encodes for the alpha-subunit of the voltage-gated sodium channel Nav1.1, responsible for GABAergic interneuron excitability. Interneuron dysfunction is evident at symptom onset in Dravet murine models, but their activity appears to recover in the chronic phase of the disease, when a series of secondary modifications arise and likely drive the phenotype. Given that the genetic basis of the disease is clear, innovative therapies based on the restoration of sufficient expression levels of Nav1.1 to re-establish functional neuronal activity are being developed. In this work, we review such therapeutic approaches, with a specific focus on the existing evidence of their ability to address not only epilepsy but also behavioral alterations, and to recover secondary modifications.