Nano-alumina induced developmental and neurobehavioral toxicity in the early life stage of zebrafish, associated with mTOR.

The study aims to investigate the effects of nano-alumina (AlNPs) on the early development and neurobehavior of zebrafish and the role of mTOR in this process. After embryos and grown-up larvae exposed to AlNPs from 0 to 200 µg/mL, we examined the development, neurobehavior, AlNPs content, and mTOR pathway genes. Moreover, embryos were randomly administered with control, negative control, mTOR knockdown, AlNPs, and mTOR knockdown + AlNPs, then examined for development, neurobehavior, oxidative stress, neurotransmitters, and development genes. As AlNPs increased, swimming speed and distance initially increased and then decreased; thigmotaxis and panic-avoidance reflex substantially decreased in the high-dose AlNPs group; aluminum and nanoparticles considerably accumulated in the 100 µg/mL AlNPs group; AlNPs at high dose decreased mTOR gene and protein levels, stimulating autophagy via increasing ULK1 and ULK2. mTOR knockdown exacerbated the harm to normal development rate, eye and body length, and neurobehavior induced by AlNPs through raising ROS, SOD, and ACH levels but decreasing AchE activity and development genes. Therefore, AlNPs suppress neurobehavior through downregulating mTOR, and mTOR knockdown further aggravates their early development and neurobehavior loss, suggesting mTOR could be a potential target for the toxicity of AlNPs.

A multi-institutional study to investigate the sparing effect after whole brain electron FLASH in mice: Reproducibility and temporal evolution of functional, electrophysiological, and neurogenic endpoints.

BACKGROUND AND PURPOSE: Ultra-high dose-rate radiotherapy (FLASH) has been shown to mitigate normal tissue toxicities associated with conventional dose rate radiotherapy (CONV) without compromising tumor killing in preclinical models. A prominent challenge in preclinical radiation research, including FLASH, is validating both the physical dosimetry and the biological effects across multiple institutions. MATERIALS AND METHODS: We previously demonstrated dosimetric reproducibility of two different electron FLASH devices at separate institutions using standardized phantoms and dosimeters. In this study, tumor-free adult female mice were given 10 Gy whole brain FLASH and CONV irradiation at both institutions and evaluated for the reproducibility and temporal evolution of multiple neurobiological endpoints. RESULTS: FLASH sparing of behavioral performance on novel object recognition (4 months post-irradiation) and of electrophysiologic long-term potentiation (LTP, 5 months post-irradiation) was reproduced between institutions. Differences between FLASH and CONV on the endpoints of hippocampal neurogenesis (Sox2, doublecortin), neuroinflammation (microglial activation), and electrophysiology (LTP) were not observed at early times (48 h to 2 weeks), but recovery of immature neurons by 3 weeks was greater with FLASH. CONCLUSION: In summary, we demonstrated reproducible FLASH sparing effects on the brain between two different beams at two different institutions with validated dosimetry. FLASH sparing effects on the endpoints evaluated manifested at later but not the earliest time points.

Prenatal exposure to PFAS and the association with neurobehavioral and social development during childhood.

Exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous and may be associated with neurodevelopmental toxicity. However, epidemiological studies report mixed results on the risks of gestational PFAS exposure for children's neurobehavioral impairment. We aimed to examine the associations between prenatal PFAS exposure and children's neurobehavioral and social problems. We measured plasma concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulphonate (PFHxS) in first-trimester blood from 757 women from the Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study. Children were assessed at 3-4 years with the Behavior Assessment System for Children-2 (BASC-2) and the Social Responsiveness Scale-2 (SRS-2) (n = 756 and 496, respectively). We used multivariable linear regression to examine associations between individual and summed log2-transformed PFAS and scores on these assessments. Effect modification by sex was evaluated through interaction terms and stratified analyses. In the sample combining both sexes, a doubling of maternal PFOA was significantly associated with lower T-scores on the following SRS-2 scales: Social Motivation, DSM-Social Communication, and SRS Total score (B ranging from -1.08 to -0.78), suggesting lesser impairments with higher exposure. In sex-stratified analysis, PFOA was related to significantly lower T-scores in boys for these BASC-2 scales: Behavioral Symptoms Index, Externalizing Problems, Aggression, and Hyperactivity (B ranging from -1.32 to -1.03). In girls, however, PFAS were significantly associated more problem behaviors, but most associations were small and the CIs included the null, with the exception of PFOA being significantly associated with higher T-scores for the BASC-2Anxiety scale (B = 1.84, 95% CI: 0.36, 3.32). In conclusion, we did not observe strong associations between prenatal exposure to the PFAS evaluated and children's neurobehavioral and social development in this population with low exposure levels. The results show mixed findings, depending on children's sex, neurodevelopmental outcome, and specific PFAS.

KANET evaluation in patients with SARS-CoV-2.

OBJECTIVES: To determine a possible correlation between SARS-CoV-2 infection during pregnancy and altered fetal behavior. METHODS: Kurjak's antenatal neurodevelopmental test (KANET) was applied from 28 to 40 weeks in 38 gestations (group A) diagnosed with COVID-19 infection during the first week and 43 non-COVID pregnant women (group B). RESULTS: No statistically significant differences considering maternal age (33±3.9 years for group A vs. 31±4.1 years for group B) and gestational age (33±1.6 weeks for group A compared to 33±2.1 weeks for group B) were observed. KANET scores were not different between the two groups. CONCLUSIONS: Fetal behavior differences are not altered in women diagnosed with SARS-CoV-2 infection during the third trimester of pregnancy.

Sex-specific effects on elements of the social brain neural network in Wistar rats from perinatal exposure to FireMaster 550 or its components.

Developmental exposure to chemical flame retardants (FRs) has been linked to a variety of neurodevelopmental disorders and abnormal socioemotional behaviors in human and laboratory animal studies. We have previously shown in Wistar rats that gestational and lactational exposure to the FR mixture Firemaster 550 (FM 550) or its brominated or organophosphate ester (OPFR) components (at 2000 µg, 1000 µg, and 1000 µg oral to the dam respectively (absolute and not by bodyweight)) results in increased anxiety-like behaviors in females and decreased sociality in both sexes. Using their siblings, this study characterized sex and chemical specific targets of disruption in brain regions underlying each behavioral phenotype. Offspring were exposed across gestation and lactation then prepared for either immunohistochemistry or autoradiography at postnatal day 90 to quantify expression of serotonin, estrogen receptor α (ERα), and oxytocin receptor (OTR) in multiple brain regions. No effect of exposure was found in males for any biological target. In females, serotonin innervation was increased in the medial amygdala of FM 550 exposed animals while ERα expression in the bed nucleus of the stria terminalis (BNST) was reduced by FM 550 and OPFR. Evidence of disrupted OTR was observed in males, particularly the BNST but considered an exploratory finding given the small sample size. These results begin to shed light on the mechanisms by which developmental FR exposure alters socioemotional behaviors of relevance to neurodevelopmental disorders.

Comparative Study of the Effects of Drugs Targeting Adrenergic Receptors on the Early Life Stages of Zebrafish.

Owing to the presence of drugs targeting adrenergic receptors in aquatic ecosystems, considerable attention has been directed towards their environmental distribution and fate in recent decades. However, their potential impacts on non-target aquatic organisms, particularly fish, have received relatively limited investigation. In this study, moxisylyte (MOX) and propranolol (PRO) were selected as representatives of α- or ß-adrenergic receptor antagonist, respectively, and we assessed their effects on the early life stages of zebrafish, especially on the nervous and cardiovascular systems. Although both compounds exhibited marginal effects on zebrafish survival, hatching and gross abnormality following exposure to concentrations ranging from 1 to 625 µg/L, they adversely affected the development of cardiovascular and nervous systems, but through different mechanisms of action, as evidenced by variations in gene transcriptional responses and enzyme activities. Notably, cardiovascular responses appear promising for use as potential biomarkers for exposure to drugs targeting adrenergic receptors. This study enhances our understanding of the ecotoxicological risks posed by α- and ß-blockers in fish. Nonetheless, further investigation is needed to elucidate the precise mechanisms underlying the impacts of drugs targeting adrenergic receptors due to our limited knowledge of the physiological functions of the adrenergic system in fish.

Dissecting the antidepressant effect of troxerutin: modulation of neuroinflammatory and oxidative stress biomarkers in lipopolysaccharide-treated mice.

The role of neuroinflammation in the pathogenesis of depression has prompted the search for new antidepressants. Troxerutin, a bioflavonoid with anti-inflammatory and antioxidant properties, has shown promise, but its impact on neurobehavioral functions remains poorly understood. This study aimed to investigate the antidepressant potential of troxerutin and its effect on the neuroinflammatory response. Here, we exposed male Swiss mice (n = 5/group) to various treatments, including naive and negative controls receiving distilled water, troxerutin-treated groups administered at different doses (10, 20, 40 mg/kg, i.p.), and an imipramine-treated group (25 mg/kg, i.p.). After seven days of treatment, with the exception of the naive group, mice were administered a single dose of lipopolysaccharide (LPS, 0.83 mg/kg). Behavioral evaluations, consisting of the novelty-suppressed feeding (NSF) test, forced swim test (FST), and open field test (OFT), were conducted. Additionally, brain samples were collected for biochemical and immunohistochemical analyses. Troxerutin significantly reduced immobility time in the FST and mitigated behavioral deficits in the NSF test. Additionally, troxerutin increased glutathione (GSH) and superoxide dismutase (SOD) levels while reducing nitrite, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ) levels compared to the negative control. Immunohistochemistry analysis revealed decreased expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) in troxerutin-treated mice. Overall, these findings suggest that troxerutin exerts significant antidepressive-like effects, likely mediated by its anti-inflammatory and antioxidant mechanisms. The reduction in neuroinflammatory and oxidative stress biomarkers, along with the improvement in behavioral outcomes, underscores troxerutin's potential as a therapeutic agent for depression.

Acute exposure to environmentally relevant concentrations of pharmaceutical pollutants induces neurobehavioral toxicity in zebrafish (Danio rerio).

Pharmaceutical waste from point and non-point sources enters, persists, or disseminates in the environment and is known as environmentally persistent pharmaceutical pollutants. Understanding the impacts of pharmaceutical pollutants on the environment and health is essential. This study investigates the behavioral impacts of pharmaceutical pollutants on aquatic organisms and delineates the possible nexus of oxidative stress. The male zebrafish were exposed to four major representative pharmaceutical pollutants, viz., acetaminophen, carbamazepine, metformin, and trimethoprim at environmentally relevant concentrations individually as well as in a mixture for seven days. Substantial alterations in social interaction, aggressive nature, novel tank exploration, and light and dark zone preferences were recorded and the degree varied to different pharmaceutical pollutants. The activity of oxidative stress markers, superoxide dismutase, glutathione-S-transferase, and catalase, was found to be suppressed to 66-20%, 42-25%, and 59-20% respectively with the elevated malondialdehyde generation (180-260%) compared to control. The activity level of acetylcholine esterase was found to be increased to 200-500% across all treatment groups. Despite the synergistic impacts of pharmaceutical pollutants on the whole system that could not be ascertained, this comprehensive study highlights their toxicity nature to induce neurobehavioral toxicity in zebrafish through oxidative stress mechanisms and altered cholinergic systems.

Thyroid and neurobehavioral effects of DiNP on GH3 cells and larval zebrafish (Danio rerio).

Diisononyl phthalate (DiNP) has been used to replace bis(2-ethylhexyl) phthalate (DEHP) and is frequently found in the environment and humans. DiNP is reported for its anti-androgenic activity; however, little is known about its effects on thyroid function and neurodevelopment. In the present study, the thyroid disruption and neurobehavioral alteration potential of DiNP and its major metabolites were assessed in a rat pituitary carcinoma cell line (GH3) and embryo-larval zebrafish (Danio rerio). In GH3 cells, exposure to DiNP and its metabolites not only increased proliferation but also induced transcriptional changes in several target genes, which were different from those observed with DEHP exposure. In larval fish, a 5-day exposure to DiNP caused significant increases in thyroid hormone levels, following a similar pattern to that reported for DEHP exposure. Following exposure to DiNP, the activity of the larval fish decreased, and neurodevelopment-related genes, such as c-fos, elavl3, and mbp, were down-regulated. These changes are generally similar to those observed for DEHP. Up-regulation of gap43 and down-regulation of elavl3 gene, which are important for both thyroid hormone production and neurodevelopment, respectively, support the potential for both thyroid and behavioral disruption of DiNP. Overall, these results emphasize the need to consider the adverse thyroid and neurodevelopmental effects in developing regulations for DEHP-replacing phthalates.

Gestational buprenorphine-naloxone exposure and fetal neurobehavior.

BACKGROUND: Buprenorphine-naloxone treatment may confer substantial benefits for the treatment of opioid use disorder (OUD) during pregnancy including lower risk for overdose/death, less diversion potential and reduced use of other substances. Treatment may also result in less severe Neonatal Abstinence Syndrome (NAS), but little is known about the effects of this medication on fetal neurodevelopment. METHODS: The purpose of the current study is to evaluate neurobehaviors among fetuses exposed to buprenorphine-naloxone at four time points over the second and third trimesters of gestation in pregnant women with OUD on buprenorphine-naloxone therapy. Sixty minutes of continuous fetal monitoring via fetal actocardiograph with a single wide array abdominal transducer took place at times of peak and trough buprenorphine-naloxone levels in 24 pregnant women. Data collection, which included measures of fetal heart rate and motor activity, was conducted between 24 and 36 weeks gestation, with the majority (84.6%) monitored at two or more gestational ages. Medication dose and other substance use was monitored throughout the study and infant NAS severity was assessed. RESULTS: Fetal heart rate (FHR), FHR variability, accelerations in FHR, and motor activity were suppressed when buprenorphine-naloxone levels were at pharmacologic peak as compared to trough concentrations at 36 weeks, but not earlier in gestation. Maternal medication dose was unrelated to infant NAS severity. CONCLUSIONS: Conclusions: There were evident subclinical fetal neurophysiological responses at times of peak maternal buprenorphine/naloxone levels in later gestation, similar to those previously described for buprenorphine only. Further studies evaluating the effects of these changes in fetal neurobehaviors on the longer-term infant development are needed.

Traumatic brain injury alters the effects of class II invariant peptide (CLIP) antagonism on chronic meningeal CLIP + B cells, neuropathology, and neurobehavioral impairment in 5xFAD mice.

BACKGROUND: Traumatic brain injury (TBI) is a significant risk factor for Alzheimer's disease (AD), and accumulating evidence supports a role for adaptive immune B and T cells in both TBI and AD pathogenesis. We previously identified B cell and major histocompatibility complex class II (MHCII)-associated invariant chain peptide (CLIP)-positive B cell expansion after TBI. We also showed that antagonizing CLIP binding to the antigen presenting groove of MHCII after TBI acutely reduced CLIP + splenic B cells and was neuroprotective. The current study investigated the chronic effects of antagonizing CLIP in the 5xFAD Alzheimer's mouse model, with and without TBI. METHODS: 12-week-old male wild type (WT) and 5xFAD mice were administered either CLIP antagonist peptide (CAP) or vehicle, once at 30 min after either sham or a lateral fluid percussion injury (FPI). Analyses included flow cytometric analysis of immune cells in dural meninges and spleen, histopathological analysis of the brain, magnetic resonance diffusion tensor imaging, cerebrovascular analysis, and assessment of motor and neurobehavioral function over the ensuing 6 months. RESULTS: 9-month-old 5xFAD mice had significantly more CLIP + B cells in the meninges compared to age-matched WT mice. A one-time treatment with CAP significantly reduced this population in 5xFAD mice. Importantly, CAP also improved some of the immune, histopathological, and neurobehavioral impairments in 5xFAD mice over the ensuing six months. Although FPI did not further elevate meningeal CLIP + B cells, it did negate the ability of CAP to reduce meningeal CLIP + B cells in the 5xFAD mice. FPI at 3 months of age exacerbated some aspects of AD pathology in 5xFAD mice, including further reducing hippocampal neurogenesis, increasing plaque deposition in CA3, altering microgliosis, and disrupting the cerebrovascular structure. CAP treatment after injury ameliorated some but not all of these FPI effects.

Cancer related cognitive impairment: a downside of cancer treatment.

Cancer treatment is associated with long lasting cognitive impairment in cancer survivors. This cognitive impairment is often termed cancer related cognitive impairment (CRCI). Cancer survivors treated for tumors outside the central nervous system are increasingly diagnosed with CRCI. The development of strategies to mitigate the negative effects of cancer treatment on the brain are crucial. Although neuroimaging research has proposed several candidate mechanisms, the pathogenic underpinnings of CRCI remain uncertain. As such, preventative and treatment strategies have not been identified. To fill these gaps, animal models play a vital role in isolating underlying contributing mechanisms that promote CRCI and in testing new therapeutic approaches.

Diet/photoperiod mediated changes in cerebellar clock genes causes locomotor shifts and imperative changes in BDNF-TrkB pathway.

Neuropsychological studies report anxiety and depression like symptoms in patients suffering from lifestyle disorder but its impact on locomotor function lacks clarity. Our study investigates locomotor deficits resulting due to perturbations in cerebellum of high fat diet (HFD), chronodisruption (CD) or a combination (HCD) model of lifestyle disorder. Significant downregulation in levels of cerebellar clock genes (Bmal-1, Clock, Per 1 and Per 2) and Bdnf-Trkb pathway genes (Bdnf, TrkB and Syn1 levels) were recorded. Further, locomotor deficits were observed in all the three experimental groups as evidenced by actimeter test, pole test and wire hanging test. Nuclear pyknosis of Purkinje cells, their derangement and inflammation were the hallmark of cerebellar tissue of all the three experimental groups. Taken together, this study generates important links between cerebellar clock oscillations, locomotor function and Bdnf-TrkB signaling.

Neurobehavioral outcomes of infants exposed to buprenorphine-naloxone compared with naltrexone during pregnancy.

BACKGROUND: Naltrexone is a medication used to treat both opioid and alcohol use disorder with limited experience in pregnant individuals, particularly in comparison to more commonly utilized treatments such as buprenorphine-naloxone. The long-term outcomes of infants exposed to naltrexone has not been previously examined. AIMS: To compare the neurobehavioral outcomes of naltrexone versus buprenorphine-naloxone exposed infants. STUDY DESIGN: Multi-centered prospective cohort study. SUBJECTS: Pregnant people on prescribed buprenorphine-naloxone or naltrexone were enrolled during pregnancy and the dyad followed until 12 months after delivery. OUTCOME MEASURES: Infants were evaluated at 4-6 weeks corrected gestational age (CGA) using the NICU Neonatal Neurobehavioral Scale (NNNS) and at the 12-month CGA visit using the Ages and Stages Questionnaire, Third Edition (ASQ-3). RESULTS: There were 7 dyads in the naltrexone group and 34 in the buprenorphine-naloxone group. On the NNNS, infants exposed to naltrexone had higher median scores for arousal and excitability, and lower median scores for attention and regulation at 4-6 weeks CGA compared to the buprenorphine-naloxone group. None of the infants in the naltrexone group were monitored for NOWS and had shorter length of hospital stay compared with the buprenorphine-naloxone group. Although no statistically significant differences were observed, more infants in the buprenorphine-naloxone group were identified as at risk for development delays in the communication, problem solving, and personal social domains of the ASQ-3 at 12 months CGA. Results should be interpreted with caution given this study's small sample size and lack of a prospective comparison cohort. CONCLUSIONS: In this small cohort, there are differences noted in infant neurobehavior by NNNS at 4-6 weeks of age when comparing the buprenorphine-naloxone and naltrexone groups. At 12 months, ASQ-3 scores were similar but with percentage differences in potential development delay risk observed between the two groups. Larger cohort studies are needed to determine the long-term child outcomes after naltrexone exposure in pregnancy.

Effects of non-ionizing radio frequency electromagnetic radiation on the development and behavior of early embryos of Danio rerio.

Biological effects of radio frequency electromagnetic radiation (RF-EMR) in the range of 900-1800 MHz emerging from the mobile phone were investigated and were found to influence the locomotor pattern when exposure was initiated from 1 hour post fertilization (hpf) in zebrafish embryos (ZE), Danio rerio. Mobile phones and other wireless devices offer tremendous advantages. However, on the flipside they are leading to an increased electromagnetic energy in the environment, an excess of which could be termed as electromagnetic pollution. Herein, we tried to understand the effects of RF-EMR emerging from the mobile phone, on the development and behavior of ZE, exposed to RF-EMR (specific absorption rate of 1.13 W/kg and 1800 MHz frequency) 1 hr daily, for 5 days. To understand if there could be any developmental stage-specific vulnerability to RF-EMR, the exposure was initiated at three different time points: 1hpf, 6hpf and 24hpf of ZE development. Observations revealed no significant changes in the survival rate, morphology, oxidative stress or cortisol levels. However, statistically significant variations were observed in the batch where exposure started at 1hpf, with respect to locomotion patterns (distance travelled: 659.1 ± 173.1 mm Vs 963.5 ± 200.4 mm), which could be correlated to anxiety-like behavior; along with a corresponding increase in yolk consumption (yolk sac area: 0.251 ± 0.019 mm2 Vs 0.225 ± 0.018 mm2). Therefore, we conclude that RF-EMR exposure influences the organism maximally during the earliest stage of development, and we also believe that an increase in the time of exposure (corresponding to the patterns of current usage of mobile phones) might reveal added afflictions.

Mobile phones and other wireless devices are on a rampant usage worldwide. They work by radiating low energy radiofrequency electromagnetic radiations. An excessive usage of wireless devices is leading to increased presence of these radiations in our surroundings. Since these radiations are not physically sensed by the organisms, its impact stays elusive. Nevertheless, the interaction of these radiations with biological systems may produce some unwarranted effects. When we exposed the ZE to the mobile phone radiation daily 1hr for 5days, our observations revealed that the youngest of the experimental group showed susceptibility. The effect was evident through haphazard movements and stressed behavior. So, it is important to be aware of the potential effects and take necessary precautions by following safety guidelines, especially when the organism is in its early life stage.

Pregestational fructose-induced metabolic syndrome in Wistar rats causes sexually dimorphic behavioral changes in their offspring.

Metabolic syndrome (MetS), marked by enduring metabolic inflammation, has detrimental effects on cognitive performance and brain structure, influencing behavior. This study aimed to investigate whether maternal MetS could negatively impact the neurodevelopment and metabolism of offspring. To test this hypothesis, 2 months old female Wistar rats were subjected to a 10-week regimen of tap water alone or supplemented with 20% fructose to induce MetS. Dams were mated with healthy males to generate litters: OC (offspring from control dams) and OMetS (offspring from dams with MetS). To isolate prenatal effects, all pups were breastfed by control nurse dams, maintaining a standard diet and water ad libitum until weaning. Behavioral assessments were conducted between postnatal days (PN) 22 and 95, and metabolic parameters were analyzed post-sacrifice on PN100. Results from the elevated plus maze, the open field, and the marble burying tests revealed a heightened anxiety-like phenotype in OMetS females. The novel object recognition test showed that exclusively OMetS males had long-term memory impairment. In the reciprocal social interaction test, OMetS displayed a lower number of social interactions, with a notable increase in "socially inactive" behavior observed exclusively in females. Additionally, in the three-chamber test, social preference and social novelty indexes were found to be lower solely among OMetS females. An increase in visceral fat concomitantly with hypertriglyceridemia was the relevant postmortem metabolic finding in OMetS females. In summary, maternal MetS leads to enduring damage and adverse effects on offspring neurobehavior and metabolism, with notable sexual dimorphism.

Doxycycline cotherapy with albendazole relieves neural function damage in C57BL/6 and BALB/c mice infected with Angiostrongylus cantonensis.

BACKGROUND: We investigated the effects of combination therapy albendazole and doxycycline in Angiostrongylus cantonensis-infected mice during early and late treatment. MATERIALS AND METHODS: C57BL/6 and BALB/c mice were divided into five groups: (i) uninfected, (ii) infected with A. cantonensis, (iii) infected + 10 mg/kg albendazole, (iv) infected + 25mg/kg doxycycline, and (v) infected + 10 mg/kg albendazole + 25 mg/kg doxycycline. We administered drugs in both early treatments started at 7-day post infections (dpi) and late treatments (14 dpi) to A. cantonensis-infected C57BL/6 and BALB/c mice. To assess the impact of these treatments, we employed the Morris water maze test to evaluate spatial learning and memory abilities, and the rotarod test to measure motor coordination and balance in C57BL/6 mice. Additionally, we monitored the expression of the cytokine IL-33 and GFAP in the brain of these mice using western blot analysis. RESULTS: In this study, A. cantonensis infection was observed to cause extensive cerebral angiostrongyliasis in C57BL/6 mice. This condition significantly affected their spatial learning and memory abilities, as assessed by the Morris water maze test, as well as their motor coordination, which was evaluated using the rotarod test. Early treatment with albendazole led to favorable recovery outcomes. Both C57BL/6 and BALB/c mice express IL-33 and GFAP after co-therapy. The differences of levels and patterns of IL-33 and GFAP expression in mice may be influenced by the balance between pro-inflammatory and anti-inflammatory signals within the immune system. CONCLUSIONS: Combination therapy with anthelmintics and antibiotics in the early stage of A. cantonensis infection, in C57BL/6 and BALB/c mice resulted in the death of parasites in the brain and reduced the subsequent neural function damage and slowed brain damage and neurobehavior impairment. This study suggests a more effective and novel treatment, and drug delivery method for brain lesions that can decrease the neurological damage of angiostrongyliasis patients.

Investigating the impact of Psidium guajava leaf hydroalcoholic extract in improving glutamatergic toxicity-induced oxidative stress in Danio rerio larvae.

Glutamate is one of the predominant excitatory neurotransmitters released from the central nervous system; however, at high concentrations, this substance may induce excitotoxicity. This phenomenon is involved in numerous neuropathologies. At present, clinically available pharmacotherapeutic agents to counteract glutamatergic excitotoxicity are not completely effective; therefore, research to develop novel compounds is necessary. In this study, the main objective was to determine the pharmacotherapeutic potential of the hydroalcoholic extract of Psidium guajava (PG) in a model of oxidative stress-induced by exposure to glutamate utilizing Danio rerio larvae (zebrafish) as a model. Data showed that treatment with glutamate produced a significant increase in oxidative stress, chromatin damage, apoptosis, and locomotor dysfunction. All these effects were attenuated by pre-treatment with the classical antioxidant N-acetylcysteine (NAC). Treatment with PG inhibited oxidative stress responsible for cellular damage induced by glutamate. However, exposure to PG failed to prevent glutamate-initiated locomotor damage. Our findings suggest that under conditions of oxidative stress, PG can be considered as a promising candidate for treatment of glutamatergic excitotoxicity and consequent neurodegenerative diseases.

Neurotoxicity of tetramethylammonium ion on larval and juvenile zebrafish: Effects on neurobehaviors and multiple biomarkers.

Tetramethylammonium hydroxide (TMAH) is an important compound that utilized and released by the rapidly expanding semiconductor industry, which could hardly be removed by the conventional wastewater treatment techniques. As a cholinergic agonist, the tetramethylammonium ion (TMA+) has been reported to induce toxicity to muscular and respiratory systems of mammals and human, however the toxicity on aquatic biota remains poorly known. We investigated the neurotoxic effects of TMA+ exposure on zebrafish, based on neurobehavior tests and a series of biomarkers. Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L, and significant alterations on swimming path angles (straight and deflective movements) occurred even at 10 mg/L. The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species (ROS) and malondialdehyde (MDA), significantly negatively related with the activities of antioxidant enzymes, but not significantly correlated with the level of acetylcholinesterase (AChE). Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress, rather than the alterations of neurotransmitter. At the highest exposure concentration (200 mg/L), TMA+ evoked more severe toxicity on zebrafish juveniles, showing significantly stronger elevation on the MDA activity, and greater inhibitions on the activities of antioxidant enzymes and AChE, suggesting juveniles were more susceptible to TMA+ exposure than larval zebrafish.

Mercuric sulfide nanoparticles suppress the neurobehavioral functions of Caenorhabditis elegans through a Skp1-dependent mechanism.

Cinnabar is the naturally occurring mercuric sulfide (HgS) and concerns about its safety have been grown. However, the molecular mechanism of HgS-related neurotoxicity remains unclear. S-phase kinase-associated protein 1 (Skp1), identified as the target protein of HgS, plays a crucial role in the development of neurological diseases. This study aims to investigate the neurotoxic effects and molecular mechanism of HgS based on Skp1 using the Caenorhabditis elegans (C. elegans) model. We prepared the HgS nanoparticles and conducted a comparative analysis of neurobehavioral differences in both wild-type C. elegans (N2) and a transgenic strain of C. elegans (VC1241) with a knockout of the SKP1 homologous gene after exposure to HgS nanoparticles. Our results showed that HgS nanoparticles could suppress locomotion, defecation, egg-laying, and associative learning behaviors in N2 C. elegans, while no significant alterations were observed in the VC1241 C. elegans. Furthermore, we conducted a 4D label-free proteomics analysis and screened 504 key proteins significantly affected by HgS nanoparticles through Skp1. These proteins play pivotal roles in various pathways, including SNARE interactions in vesicular transport, TGF-beta signaling pathway, calcium signaling pathway, FoxO signaling pathway, etc. In summary, HgS nanoparticles at high doses suppress the neurobehavioral functions of C. elegans through a Skp1-dependent mechanism.