Neurobehavioral Effects Research Articles

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.

Integrating developmental neuroscience with community-engaged approaches to address mental health outcomes for housing-insecure youth: Implications for research, practice, and policy

One in three children in the United States is exposed to insecure housing conditions, including unaffordable, inconsistent, and unsafe housing. These exposures have detrimental impacts on youth mental health. Delineating the neurobehavioral pathways linking exposure to housing insecurity with children’s mental health has the potential to inform interventions and policy. However, in approaching this work, carefully considering the lived experiences of youth and families is essential to translating scientific discovery to improve health outcomes in an equitable and representative way. In the current paper, we provide an introduction to the range of stressful experiences that children may face when exposed to insecure housing conditions. Next, we highlight findings from the early-life stress literature regarding the potential neurobehavioral consequences of insecure housing, focusing on how unpredictability is associated with the neural circuitry supporting cognitive and emotional development. We then delineate how community-engaged research (CEnR) approaches have been leveraged to understand the effects of housing insecurity on mental health, and we propose future research directions that integrate developmental neuroscience research and CEnR approaches to maximize the impact of this work. We conclude by outlining practice and policy recommendations that aim to improve the mental health of children exposed to insecure housing.

Persisting neurobehavioral consequences of daily or intermittent paternal cannabis administration in F1 and F2 Rats

Repeated paternal preconception exposure to Δ9-tetrahydrocannabinol (Δ9-THC) alone or together with the other constituents in a cannabis extract has been shown in our earlier studies in rats to cause significant neurobehavioral impairment in their offspring. In the current study, we compared the effects of daily cannabis extract (CE) exposure to cannabis on two consecutive days per week, modeling weekend cannabis use in human. The CE contained Δ9-THC as well as cannabidiol and cannabinol. We also extended the investigation of the study to cross-generational effects of grand-paternal cannabis exposure on the F2 generation and included testing the effects of paternal cannabis exposure on responding for opiate self-administration in F1 and F2 generation offspring. We replicated the findings of neurobehavioral impairment in F1 offspring of male rats exposed to cannabis extract containing 4 mg/kg/day of Δ9-THC daily for four weeks prior to mating with drug naïve females. The 4-week cannabis extract exposure caused a significant decrease in weight gain in the male rats exposed daily. In contrast, their offspring showed significantly greater body weights and anogenital distances (AGD) in the third to fourth weeks after birth. The behavioral effects seen in the F1 generation were increased habituation of locomotor activity in the figure-8 maze in female offspring and increased lever pressing for the opiate drug remifentanil in male offspring. The F2 generation showed significantly impaired negative geotaxis and an elimination of the typical sex-difference in locomotor activity, with effects not seen in the F1 generation. This study shows that daily paternal cannabis exposure for four weeks prior to mating causes significant neurobehavioral impairment in the F1 and F2 offspring. Intermittent exposure on two consecutive days per week for four weeks caused comparable neurobehavioral impairment. In sum, there should be concern about paternal as well as maternal exposure to cannabis concerning neurobehavioral development of their offspring.

Gastrodin ameliorates neuroinflammation in Alzheimer's disease mice by inhibiting NF-κB signaling activation via PPARγ stimulation.

We investigated the effects and targets of gastrodin (GAS) for improving cognitive ability in Alzheimer's disease (AD). The targets and mechanisms of GAS were analyzed by network pharmacology. Morris water and eight-arm radial mazes were used to detect the behaviors of 7-months-old APP/PS1 mice. The levels of IBA-1 and PPARγ were examined by histochemical staining, nerve cells were detected by Nissl staining, inflammatory cytokines were measured by ELISA, and protein expressions were monitored by Western blotting. The neurobehavioral effects of GAS on mice were detected after siRNA silencing of PPARγ. Microglia were cultured in vitro and Aβ1-42 was used to simulate the pathology of AD. After treatment with GAS, the levels of inflammatory cytokines and proteins were assayed. Network pharmacological analysis revealed that PPARγ was the action target of GAS. By stimulating PPARγ, GAS inhibited NF-κB signaling activation and decreased neuroinflammation and microglial activation, thereby ameliorating the cognitive ability of AD mice. After silencing PPARγ, GAS could not further improve such cognitive ability. Cellular-level results demonstrated that GAS inhibited microglial injury, reduced tissue inflammation, and activated PPARγ. GAS can regulate microglia-mediated inflammatory response by stimulating PPARγ and inhibiting NF-κB activation, representing a mechanism whereby it improves the cognitive behavior of AD.

Neurobehavioral Effects of Counterconditioning in Individuals With PTSD

Neurobehavioral Effects of Counterconditioning in Individuals With PTSD

Effects of Microplastics on Mental Health

The impact of microplastics on mental health is an emerging area of research, and the medical literature points to potential neurobehavioral effects. Studies have shown that exposure to microplastics can lead to changes in behavior, neurotoxicity, and cognitive impairments in animal models. Although these findings from animal studies suggest a possible link between microplastic exposure and mental health outcomes, it is important to note that research in this area is still limited and more studies are needed to understand the mechanisms and consequences for human health.

Effects of parietal repetitive transcranial magnetic stimulation in prolonged disorders of consciousness: A pilot study

ObjectiveAlthough the parietal cortex is related to consciousness, the dorsolateral prefrontal and primary motor cortices are the usual targets for repetitive transcranial magnetic stimulation (rTMS) for prolonged disorders of consciousness (pDoC). Herein, we applied parietal rTMS to patients with pDoC, to verify its neurobehavioral effects and explore a new potential rTMS target. Materials and methodsTwenty-six patients with pDoC were assigned to a rTMS or sham group. The rTMS group received 10 sessions of parietal rTMS; the sham group received 10 sessions of sham stimulation. The Coma Recovery Scale-Revised (CRS-R) and event-related potential (ERP) were collected before and after the 10 sessions or sham sessions. ResultsAfter the 10 sessions, the rTMS group showed: a significant CRS-R score increase; ERP appearance of a P300 waveform and significantly increased Fz amplitudes; increased potentials on topographic mapping, especially in the left prefrontal cortex; and an increase in delta and theta band powers at Fz, Cz, and Pz. The sham group did not show such changes in CRS-R score or ERP results statistically. ConclusionParietal rTMS shows promise as a novel intervention in the recovery of consciousness in pDoC. It showed neurobehavioral enhancement of residual brain function and may promote frontal activity by enhancing frontal–parietal connections. The parietal cortex may thus be an alternative for rTMS therapy protocols.

Effect of Volatile Organic Compounds on Pulmonary Functions Among Paint Industry Workers of Unorganized Sectors.

Background Paint industry workers are constantly exposed to paints and organic solvents that contain a substantial quantity of volatile organic compounds (VOCs). Exposure to VOC emissions could result in pulmonary, neurobehavioral, and hematological consequences. Limited studies have been undertaken in India to assess the health consequences of VOCs among paint industry workers in unorganized sectors. Aim To assess the effects of VOCs on pulmonary function in paint industry workers of unorganized sectors. Methodology A hundred and twenty full-time male construction painters and small-scale paint manufacturing workers aged 25-60 were assessed for respiratory symptoms using a questionnaire, and pulmonary functions using Wright's Peak Expiratory Flow Meter (PEFR). Participants were randomly selected forVOC assessment andthe cumulative solvent exposure index was calculated. A pulmonary function test (PFT) was performed on a subset of construction painters (n=30) using a Koko spirometer. Results The concentration of VOCs such as benzene, ethylbenzene, toluene, and xylene (BETX) and dichloromethane levels exceeded American Conference of Governmental Industrial Hygienists (ACGIH)threshold limit values (TLVs) among the paint manufacturing workers. About 52% of paint workers reported respiratory symptoms. Around 22% of the participants showedreduced pulmonary function (PEFR<400 L/min). There was a significant weaknegativecorrelationbetween PEFR andwork experience (r = -0.2, p=0.03). PFT parameters among a subset of construction painters revealed a significant moderate negative correlation with work experience [forced expiratory volume at the onset of the first second (FEV1) (r = -0.6, p=0.001) and forced vital capacity (FVC) (r = -0.53, p=0.005)] and cumulative VOC exposure index [FEV1 (r = -0.53, p = 0.004) and FVC (r = -0.5, p = 0.008)]. Conclusion The concentration of VOCs was higher among paint industry workers of unorganized sectors and they reported respiratory symptoms and diminished pulmonary function. To reduce morbidity, it is critical to enhance awareness about occupational safety and services in these unorganized sectors.

Exploring the anti-inflammatory, sedative, antidiabetic, and antioxidant potential in in-vitro and in-vivo models and phenolic profiling of Atractylis aristata Batt.

Ethnopharmacological relevanceAtractylis aristata batt., as an endemic plant from the Asteraceae family, holds a significant position in the Ahaggar region of southern Algeria's traditional medicine. The aerial parts of Atractylis aristata was used to cure inflammation, fever, and stomach disorders. Aim of the studyThe objective of the present investigation was to ascertain the overall bioactive components and phytochemical components and examine the antioxidant, antidiabetic, anti-inflammatory, acute toxicity, and sedative properties of the crude extract obtained from the aerial portions of Atractylis aristata (AaME). Materials and methodsThe AaME's antioxidant activity was assessed by the use of pyrogallol autoxidation, (1,1 diphenyl-2-picrylhydrazyl) (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and reducing power (RP) techniques. 1 mg/mL of AaME was used to evaluate the antidiabetic activity by applying the enzyme α-amylase inhibitory power test. At the same time, the bovine serum albumin (BSA) denaturation method was employed to quantify the in vitro anti-inflammatory activity at different concentrations (1.5625, 0.78125, 0.390625, 0.1953125 and 0.09765625 mg/mL). In contrast, following the Organization for Economic Co-operation and Development (OECD) guideline No. 423, which covers acute oral toxicity testing protocols, the limit dosage test was employed to assess in vivo acute toxicity. At the dose of 0.08 mg/mL, the carrageenan-induced paw edema approach was used to assess the anti-inflammatory efficacy in vivo, and the sedative activity was carried out at the dose of 0.08 mg/mL using the measurement of the locomotor method. Different bioactive compounds were identified within AaME using LC-MS/MS and HPLC-UV analysis. ResultsThe acute toxicity study showed no fatalities or noticeable neurobehavioral consequences at the limit test; this led to their classification in Globally Harmonized System (GHS) category Five, as the OECD guideline No 423 recommended. At a concentration of 0.08 mg/mL (2000 mg/kg), AaME showed apparent inhibition of paw edema and a significant (p = 0.01227) reduction in locomotor activity compared to the control animals. Our findings showed that AaME exhibited considerable antioxidant (IC50 = 0.040 ± 0.003 mg/mL (DPPH), IC50 = 0.005 ± 5.77 × 10-5 mg/mL (ABTS), AEAC = 91.15 ± 3.921 mg (RP) and IR% = 23.81 ± 4.276 (Inhibition rate of pyrogallol) and rebuts antidiabetic activities (I% = 57.6241% ± 2.81772). Our findings revealed that the maximum percentage of BSA inhibition (70.84 ± 0.10%) was obtained at 1.562.5 mg/mL. Thus, the AaME phytochemical profile performed using phytochemical screening, HPLC-UV, and LC-MS/MS analysis demonstrated that A. aristata can be a valuable source of chemicals with biological activity for pharmaceutical manufacturers. ConclusionThe phytochemical profiling, determined through HPLC-UV and LC-MS/MS applications, reveals this plant's therapeutic value. The aerial parts of Atractylis aristata contain bioactive molecules such as gallic acid, ascorbic acid, and quercetin, contributing to its significant antioxidant capabilities. Furthermore, identifying alizarin, the active compound responsible for its anti-inflammatory properties, could provide evidence supporting the anti-inflammatory capabilities of this subspecies.

Shaking Up Our Approach: The Need for Characterization and Optimization of Pre-clinical Models of Infant Abusive Head Trauma.

Traumatic brain injuries (TBIs) are a large societal and individual burden. In the first year of life, the vast majority of these injuries are the result of inflicted abusive events by a trusted caregiver. Abusive head trauma (AHT) in infants, formerly known as shaken baby syndrome, is the leading cause of inflicted mortality and morbidity in this population. In this review we address clinical diagnosis, symptoms, prognosis, and neuropathology of AHT, emphasizing the burden of repetitive AHT. Next, we consider existing animal models of AHT, and we evaluate key features of an ideal model, highlighting important developmental milestones in children most vulnerable to AHT. We draw on insights from other injury models, such as repetitive, mild TBIs (RmTBIs), post-traumatic epilepsy (PTE), hypoxic-ischemic injuries, and maternal neglect, to speculate on key knowledge gaps and underline important new opportunities in pre-clinical AHT research. Finally, potential treatment options to facilitate healthy development in children following an AHT are considered. Together, this review aims to drive the field toward optimized, well-characterized animal models of AHT, which will allow for greater insight into the underlying neuropathological and neurobehavioral consequences of AHT.

Corn oil and Soybean oil effect as vehicles on behavioral and oxidative stress profiles in developmentally exposed offspring mice

Corn and soybean oils are among the most frequently used vehicles for water-insoluble compounds in toxicological studies. These two vegetable oils are nutrients and may induce some biological effects on animals that might interfere with the experimental results. However, their chronic effects on a developing brain have not been reported. This study aims to evaluate the neurobehavioral and brain biochemical effects of both oils on male and female Swiss albino mice. Pregnant female mice were exposed to 1 µl/g/d of either tap water, corn oil (CO), or soybean oil (SO) from early gestation (GD1) until weaning then offspring mice were exposed to the same treatment regimen until adulthood (PND70). Our results showed that developmental exposure to both oils induced body weight changes in offspring mice. In addition, we detected some behavioral abnormalities where both oil-treated groups showed a significant decrease in locomotor activity and greater levels of anxiety behavior. Moreover, our results suggest that continuous exposure to these oils may alter motor coordination, spatial memory and induce depression-like behavior in adult mice. These alterations were accompanied by increased malondialdehyde, superoxide dismutase, and glutathione peroxidase activities in specific brain regions. Together, these data suggest that exposure to CO and SO as vehicles in developmental studies may interfere with the behavioral response and brain redox homeostasis in offspring mice.

Early-Life Lead Exposure: Risks and Neurotoxic Consequences.

Lead (Pb) does not have any biological function in a human, and it is likely no safe level of Pb in the human body. The Pb exposure impacts are a global concern for their potential neurotoxic consequences. Despite decreasing both the environmental Pb levels and the average blood Pb levels in the survey populations, the lifetime redistribution from the tissues-stored Pb still poses neurotoxic risks from the low-level exposure in later life. The growing fetus and children hold their innate high-susceptible to these Pb-induced neurodevelopmental and neurobehavioral effects. This article aims to evaluate cumulative studies and insights on the topic of Pb neurotoxicology while assessing the emerging trends in the field. The Pb-induced neurochemical and neuro-immunological mechanisms are likely responsible for the high-level Pb exposure with the neurodevelopmental and neurobehavioral impacts at the initial stages. Early-life Pb exposure can still produce neurodegenerative consequences in later life due to the altered epigenetic imprints and the ongoing endogenous Pb exposure. Several mechanisms contribute to the Pb-induced neurotoxic impacts, including the direct neurochemical effects, the induction of oxidative stress and inflammation through immunologic activations, and epigenetic alterations. Furthermore, the individual nutritional status, such as macro-, micro-, or antioxidant nutrients, can significantly influence the neurotoxic impacts even at low-level exposure to Pb. The prevention of early-life Pb exposure is, therefore, the critical determinant for alleviating various Pb-induced neurotoxic impacts across the different age groups.

Impaired extinction of cocaine seeking in HIV-infected mice is accompanied by peripheral and central immune dysregulation

Substance use disorders (SUDs) are highly comorbid with HIV infection, necessitating an understanding of the interactive effects of drug exposure and HIV. The relationship between HIV infection and cocaine use disorder is likely bidirectional, with cocaine use directly impacting immune function while HIV infection alters addiction-related behavior. To better characterize the neurobehavioral and immune consequences of HIV infection and cocaine exposure, this study utilizes a humanized mouse model to investigate the outcomes of HIV-1 infection on cocaine-related behaviors in a conditioned place preference (CPP) model, and the interactive effects of cocaine and HIV infection on peripheral and central nervous system inflammation. HIV infection selectively impairs cocaine CPP extinction without effecting reinstatement or cocaine seeking under conflict. Behavioral alterations are accompanied by immune changes in HIV infected mice, including increased prefrontal cortex astrocyte immunoreactivity and brain-region specific effects on microglia number and reactivity. Peripheral immune system changes are observed in human cytokines, including HIV-induced reductions in human TNFα, and cocaine and HIV interactions on GM-CSF levels. Together these data provide new insights into the unique neurobehavioral outcomes of HIV infection and cocaine exposure and how they interact to effect immune responses.

Social isolation and post-weaning environmental enrichment effects on rat emotional behavior and serotonergic system.

Social isolation (SI) is related to adverse neurobehavioral effects and neurochemical changes when it occurs early in development. On the other hand, environmental enrichment (EE) is associated with a reduction in anxiety-like and depression-like behavior, as well as an increase in serotonin (5-HT) levels in the prefrontal cortex and hippocampus in rodents. This study systematically reviewed the effects of SI and EE on emotional behavior and serotonergic system components in rats after weaning. Primary experimental studies that used subgroups of rats subjected to SI, EE, and normal social conditions after weaning were considered eligible. Studies that used transgenic rodents, ex vivo studies, in vitro studies, human research, or in silico studies were ineligible. Two authors completed searches in Medline/PubMed, LILACS, Scopus, Web of Science, EMBASE, and Open Gray. The Kappa index was calculated to assess agreement between reviewers and assess study quality. The results showed that the animals exposed to EE showed better adaptation to a new environment. Furthermore, EE increased 5-HT levels in the hippocampus and prefrontal cortex of rodents. Thus, it appears that an EE during the critical period of development may reduce anxiety/depression-like behaviors, as well as increase long-term neurotransmitter response.

Methoxsalen Inhibits the Acquisition of Nicotine Self-Administration: Attenuation by Cotinine Replacement in Male Rats.

Cigarette smoking remains the leading preventable cause of disease and death. Nicotine is the primary reinforcing ingredient in cigarettes sustaining addiction. Cotinine is the major metabolite of nicotine that produces a myriad of neurobehavioral effects. Previous studies showed that cotinine-supported self-administration in rats and rats with a history of cotinine self-administration exhibited relapse-like drug-seeking behavior, suggesting that cotinine may also be reinforcing. To date, whether cotinine may contribute to nicotine reinforcement remains unknown. Nicotine metabolism is mainly catalyzed by hepatic CYP2B1/2 enzymes in rats and methoxsalen is a potent CYP2B1/2 inhibitor. The study examined nicotine metabolism, self-administration, and locomotor activity. The hypothesis is that methoxsalen inhibits nicotine self-administration and cotinine replacement attenuates the inhibitory effects of methoxsalen in male rats. Methoxsalen decreased plasma cotinine levels following a subcutaneous nicotine injection. Repeated daily methoxsalen treatments reduced the acquisition of nicotine self-administration, leading to fewer nicotine infusions, lower nicotine intake, and lower plasma cotinine levels. However, methoxsalen did not alter the maintenance of nicotine self-administration despite a significant reduction of plasma cotinine levels. Cotinine replacement by mixing cotinine with nicotine for self-administration dose-dependently increased plasma cotinine levels and enhanced the acquisition of self-administration. Neither basal nor nicotine-induced locomotor activity was altered by methoxsalen. These results indicate that methoxsalen inhibition of cotinine formation impaired the acquisition of nicotine self-administration, and cotinine replacement attenuated the inhibitory effects of methoxsalen on the acquisition of self-administration, suggesting that cotinine may contribute to the initial development of nicotine reinforcement. Smoking cessation medications targeting nicotine's effects are only moderately effective, making it imperative to better understand the mechanisms of nicotine misuse. Methoxsalen inhibited nicotine metabolism to cotinine and impaired the acquisition of nicotine self-administration. Cotinine replacement restored plasma cotinine and attenuated the methoxsalen inhibition of nicotine self-administration in rats. These results suggest that (1) the inhibition of nicotine metabolism may be a viable strategy in reducing the development of nicotine reinforcement, (2) methoxsalen may be translationally valuable, and (3) cotinine may be a potential pharmacological target for therapeutic development given its important role in the initial development of nicotine reinforcement.

Cyfluthrin exposure during pregnancy causes neurotoxicity in offspring—Ca2+ overload via IP3R-GRP75-VDAC1 pathway

Cyfluthrin (Cy) is a widely used pyrethroid insecticide. There is growing evidence that Cy can cause damage to the nervous, reproductive, and immune systems, but there is limited evidence on the potential effects of maternal Cy exposure on offspring. A model of maternal Cy exposure was used to assess its neurobehavioral effects on young-adult offspring. We found that gestational Cy exposure affected pregnancy outcomes and fetal development, and that offspring showed impairments in anxiety as well as learning and memory, accompanied by impairments in hippocampal synaptic ultrastructure and synaptic plasticity. In addition, the IP3R-GRP75-VDAC1 apoptogenic pathway was also upregulated, and in vitro models showed that inhibition of this pathway alleviated neuronal apoptosis as well as synaptic plasticity damage. In conclusion, maternal Cy exposure during pregnancy can cause neurobehavioral abnormalities and synaptic damage in offspring, which may be related to neuronal apoptosis induced by activation of the IP3R-GRP75-VDAC1 pathway in the hippocampus of offspring. Our findings provide clues to understand the neurotoxicity mechanism of maternal Cy exposure to offspring during pregnancy.

Embryonic exposures to cadmium and PAHs cause long-term and interacting neurobehavioral effects in zebrafish

Developmental exposure to either polycyclic aromatic hydrocarbons (PAHs) or heavy metals has been shown to cause persisting and overlapping neurobehavioral effects in animal models. However, interactions between these compounds have not been well characterized, despite their co-occurrence in a variety of environmental media. In two companion studies, we examined the effects of developmental exposure to cadmium (Cd) with or without co-exposure to prototypic PAHs benzo[a]pyrene (BaP, Exp. 1) or fluoranthene (FA, Exp. 2) using a developing zebrafish model. Zebrafish embryos were exposed to Cd (0–0.3 μM), BaP (0–3 μM), FA (0–1.0 μM), or binary Cd-PAH mixtures from 5 to 122 h post fertilization (hpf). In Exp. 1, Cd and BaP produced independent effects on an array of outcomes and interacting effects on specific outcomes. Notably, Cd-induced deficits in dark-induced locomotor stimulation were attenuated by BaP co-exposure in the larval motility test and BaP-induced hyperactivity was attenuated by Cd co-exposure in the adolescent novel tank test. Likewise, in Exp. 2, Cd and FA produced both independent and interacting effects. FA-induced increases on adult post-tap activity in the tap startle test were attenuated by co-exposure with Cd. On the predator avoidance test, FA- and 0.3 μM Cd-induced hyperactivity effects were attenuated by their co-exposure. Taken together, these data indicate that while the effects of Cd and these representative PAHs on zebrafish behavior were largely independent of one another, binary mixtures can produce sub-additive effects for some neurobehavioral outcomes and at certain ages. This research emphasizes the need for detailed risk assessments of mixtures containing contaminants of differing classes, and for clarity on the mechanisms which allow cross-class toxicant interactions to occur.

Low blood concentration of alcohol enhances activity related to stopping failure in the right inferior frontal cortex.

This study investigated the effects of low doses of alcohol, which are acceptable for driving a car, on inhibitory control and neural processing using the stop-signal task (SST) in 17 healthy right-handed social drinkers. The study employed simultaneous functional magnetic resonance imaging and electromyography (EMG) recordings to assess behavioral and neural responses under conditions of low-dose alcohol (breath-alcohol concentration of 0.15mg/L) and placebo. The results demonstrated that even a small amount of alcohol consumption prolonged Go reaction times in the SST and modified stopping behavior, as evidenced by a decrease in the frequency and magnitude of partial response EMG that did not result in button pressing during successful inhibitory control. Furthermore, alcohol intake enhanced neural activity during failed inhibitory responses in the right inferior frontal cortex, suggesting its potential role in behavioral adaptation following stop-signal failure. These findings suggest that even low levels of alcohol consumption within legal driving limits can greatly impact both the cognitive performance and brain activity involved in inhibiting responses. This research provides important evidence on the neurobehavioral effects of low-dose alcohol consumption, with implications for understanding the biological basis of impaired motor control and decision-making and potentially informing legal guidelines on alcohol consumption.

The psychomotor, reinforcing, and discriminative stimulus effects of synthetic cathinone mexedrone in male mice and rats

The chronic use of the novel synthetic cathinone mexedrone, like other psychoactive drugs, can be considered addictive, with a high potential for abuse and the ability to cause psychological dependence in certain users. However, little is known about the neurobehavioral effects of mexedrone in association with its potential for abuse. We investigated the abuse potential for mexedrone abuse through multiple behavioral tests. In addition, serotonin transporter (SERT) levels were measured in the synaptosome of the dorsal striatum, and serotonin (5-HT) levels were measured in the dorsal striatum of acute mexedreone (50 mg/kg)-treated mice. To clarify the neuropharmacological mechanisms underlying the locomotor response of mexedrone, the 5-HT2A receptor antagonist M100907 (0.5 or 1.0 mg/kg) was administered prior to the acute injection of mexedrone in the locomotor activity experiment in mice. Mexedrone (10–50 mg/kg) produced a significant place preference in mice and mexedrone (0.1–0.5 mg/kg/infusion) maintained self-administration behavior in rats in a dose-dependent manner. In the drug discrimination experiment, mexedrone (5.6–32 mg/kg) was fully substituted for the discriminative stimulus effects of cocaine in rats. Mexedrone increased locomotor activity, and these effects were reversed by pretreatment with M100907. Acute mexedrone significantly increased c-Fos expression in the dorsal striatum and decreased SERT levels in the synaptosome of the dorsal striatum of mice, resulting in an elevation of 5-HT levels. Taken together, our results provide the possibility that mexedrone has abuse potential, which might be mediated, at least in part, by the activation of the serotonergic system in the dorsal striatum.

Polystyrene Nano- and Microplastic Particles Induce an Inflammatory Gene Expression Profile in Rat Neural Stem Cell-Derived Astrocytes In Vitro.

Microplastics are considered an emerging environmental pollutant due to their ubiquitous presence in the environment. However, the potential impact of microplastics on human health warrants further research. Recent studies have reported neurobehavioral and neurotoxic effects in marine and rodent models; however, their impact on the underlying cellular physiology in mammals remains unclear. Herein, we exposed neural stem cells and neural stem cell-derived astrocytes, oligodendrocytes, and neurons to various sizes and concentrations of polystyrene nano- and microplastics. We investigated their cellular uptake, impact on cytotoxicity, and alteration of gene expression through transcriptome profiling. The cell type most affected by decreased viability were astrocytes after 7 days of repeated exposure. Transcriptional analysis showed that 1274 genes were differentially expressed in astrocytes exposed to 500 nm microplastics, but only 531 genes were altered in astrocytes exposed to 50 nm nanoplastics. Both canonical pathway and Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated pathways were involved in neuroinflammation, innate and adaptive immunity, cell migration, proliferation, extracellular matrix remodeling, and cytoskeleton structures. The downregulated pathways were involved in lipid metabolism, specifically fatty acid oxidation and cholesterol metabolism. Our results show that neural stem cell-derived astrocytes repeatedly exposed to nano- and microplastics for 7 days undergo changes that are hallmarks of astrogliosis.