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Contextual fear conditioning is a protocol used to assess associative learning across species, including fish. Here, our goal was to expand the analysis of behavioral parameters that may reflect aversive behaviors in a contextual fear conditioning protocol using adult zebrafish (Danio rerio) and to verify how such parameters can be modulated. First, we analyzed the influence of an aversive stimulus (3 mild electric shocks for 5 s each at frequencies of 10, 100 or 1000 Hz) on fish behavior, and their ability to elicit fear responses in the absence of shock during a test session. To confirm whether the aversive responses are context-dependent, behaviors were also measured in a different experimental environment in a test session. Furthermore, we investigated the effects of dizocilpine (MK-801, 2 mg/kg, i.p.) on fear-related responses. Zebrafish showed significant changes in baseline activity immediately after shock exposure in the training session, in which 100 Hz induced robust contextual fear responses during the test session. Importantly, when introduced to a different environment, animals exposed to the aversive stimulus did not show any differences in locomotion and immobility-related parameters. MK-801 administered after the training session reduced fear responses during the test, indicating that glutamate NMDA-receptors play a key role in the consolidation of contextual fear-related memory in zebrafish. In conclusion, by further exploring fear-related behaviors in a contextual fear conditioning task, we show the effects of different shock frequencies and confirm the importance of context on aversive responses for associative learning in zebrafish. Additionally, our data support the use of zebrafish in contextual fear conditioning tasks, as well as for advancing pharmacological studies related to associative learning in translational neurobehavioral research.
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Conducta Animal , Condicionamiento Clásico , Maleato de Dizocilpina , Electrochoque , Antagonistas de Aminoácidos Excitadores , Miedo , Pez Cebra , Animales , Miedo/efectos de los fármacos , Miedo/fisiología , Maleato de Dizocilpina/farmacología , Condicionamiento Clásico/efectos de los fármacos , Condicionamiento Clásico/fisiología , Antagonistas de Aminoácidos Excitadores/farmacología , Conducta Animal/efectos de los fármacos , Masculino , Aprendizaje por Asociación/efectos de los fármacos , Aprendizaje por Asociación/fisiología , Femenino , Locomoción/efectos de los fármacosRESUMEN
When liver or intestinal function is impaired, bilirubin accumulates in the body and leads to neonatal jaundice. However, the potential negative effects caused by excessive accumulation of bilirubin such as developmental immunotoxicity and neurotoxicity remain unclear. We used a zebrafish model to establish bilirubin-induced jaundice symptoms and evaluated the toxic effects of bilirubin in aquatic organisms. Firstly, our results suggested that bilirubin exposure markedly decreased the survival rate, induced the developmental toxicity and increased the yellow pigment deposited in the zebrafish tail. Meanwhile, the number of macrophages and neutrophils was substantially reduced in a concentration-dependent manner. Besides, the antioxidant enzyme activities were greatly elevated while the inflammatory genes were significantly decreased after bilirubin exposure. Secondly, transcriptome analysis identified 708 genes were differentially expressed after bilirubin exposure, which animal organ morphogenesis, chemical synaptic transmission, and MAPK / mTOR signaling pathways were significantly enriched. Thirdly, bilirubin exposure leads to a significant decrease in the motility of zebrafish, including a dose-dependent decrease in the travelled distance, movement time, and average velocity. Moreover, the innate immune genes and apoptosis-related genes such as TLR4, NF-κB p65, STAT3 and p53 were elevated at a concentration of 10 µg/mL of bilirubin. Finally, our results further revealed that the anti-inflammatory and neuroprotective minocycline could partially rescue the bilirubin-induced neurobehavioral disorders in zebrafish embryos. In conclusion, our study explored the bilirubin-induced immunotoxicity and neurotoxicity in aquatic organisms, which will provide a theoretical basis for the treatment of neonatal jaundice in clinical practice.
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Ictericia Neonatal , Contaminantes Químicos del Agua , Animales , Pez Cebra/metabolismo , Minociclina/farmacología , Bilirrubina , Ictericia Neonatal/metabolismo , Inmunidad Innata , Estrés Oxidativo , Antioxidantes/farmacología , Embrión no Mamífero , Contaminantes Químicos del Agua/toxicidadRESUMEN
Primrose syndrome (PS) is a rare genetic disease characterized by developmental delay, intellectual disability, sensorineural hearing loss, and dysmorphic features. PS is caused by de novo pathogenic variants in the ZBTB20 gene, which encodes a transcription factor modulating neurogenesis. We describe resolution with sertraline of neurobehavioral difficulties in a 17-year-old Hispanic male with PS with de novo heterozygous c.1916G > A (p.C639Y) variant of ZBTB20. Neurobehavioral difficulties included aggression towards self and others, irritability, tearfulness, and mood liability that did not respond to behavioral interventions or aripiprazole. Treatment with sertraline, a medication indicated for psychiatric disorders including anxiety and depression, led to the resolution of neurobehavioral difficulties after 2 weeks of initiation of medication. The treatment course suggests that selective serotonin reuptake inhibitors, such as sertraline, may be a useful tool for neurobehavioral difficulties in PS over antipsychotics that are accompanied by complex side effect profiles, and suggest that anxiety is the primary cause of the neurobehavioral difficulties in this patient.
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Discapacidad Intelectual , Sertralina , Factores de Transcripción , Humanos , Sertralina/uso terapéutico , Masculino , Adolescente , Discapacidad Intelectual/genética , Discapacidad Intelectual/tratamiento farmacológico , Factores de Transcripción/genética , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Anomalías Múltiples/genética , Anomalías Múltiples/tratamiento farmacológico , Anomalías Múltiples/psicología , Calcinosis , Enfermedades del Oído , Atrofia Muscular , Proteínas del Tejido NerviosoRESUMEN
OBJECTIVE: Patients with traumatic brain injury (TBI) often present with seizures (functional and/or epileptic), but treatments for patients with TBI and seizures are limited. We examined treatment phase and 1-year post-enrollment outcomes following neurobehavioral therapy (NBT) for patients with TBI + functional seizures (FS) and TBI + epilepsy. METHODS: In this multicenter, prospective, three-group, nonrandomized, controlled trial, with 1-year post-enrollment follow-up, three cohorts of adults were recruited: TBI + video-electroencephalography (EEG)-confirmed FS (n = 89), TBI + EEG-confirmed epilepsy (n = 29), and chart/history-confirmed TBI without seizures (n = 75). Exclusion criteria were recent psychotic or self-injurious behavior, current suicidal ideation, pending litigation or long-term disability, active substance use disorder, and inability to participate in study procedures. TBI + FS and TBI + epilepsy groups completed NBT for seizures, an evidence-based, 12-session, multimodal psychotherapy, whereas TBI without seizures participants received standard medical care. The primary outcome was change in seizure frequency; secondary outcomes were changes in mental health, TBI-related symptoms, disability, and quality of life. RESULTS: Reductions in average monthly seizures occurred during treatment in TBI + FS participants (p = .002) and were significant from baseline (mean = 16.75; 95% confidence interval [CI] = 11.44-24.53) to 12 months post-enrollment (mean = 7.28, 95% CI = 4.37-12.13, p = .002, d = .38). Monthly seizures decreased during treatment in TBI + epilepsy participants (p = .002); reductions were not statistically significant from baseline (mean = 2.38, 95% CI = 1.12-5.04) to 12-month postenrollment (mean = .98, 95% CI = .40-2.42, p = .07, d = .22). Regarding treatment-phase changes in secondary outcome measures, TBI + FS participants improved significantly on 10 of 19 variables (52.6%), TBI + epilepsy participants improved on five of 19 (26.3%), and TBI-only comparisons improved on only one of 19 (5.3%). SIGNIFICANCE: NBT benefited patients with TBI + FS and TBI + epilepsy. Improvements were demonstrated at 1 year post-enrollment in those with TBI + FS. NBT may be a clinically useful treatment for patients with seizures.
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Cisplatin, a chemotherapy drug containing platinum, is considered a neurotoxic agent. On the other hand, crocin, the primary component of saffron, possesses neuroprotective and antioxidant properties. In this study, 28 healthy adult male Wistar rats weighing 200-250 g were used (6-7 weeks old). Rats were divided into a control group (Ctr), a crocin group (Cro), a cisplatin group (Cis), and a crocin with cisplatin group (Cro + Cis). Rotarod, open field, and shuttle box tests were performed to assess balance, explorative behavior, and avoidance memory. After behavioral testing, the hippocampus was extracted to analyze oxidative stress parameters such as GPx (glutathione peroxidase), SOD (superoxide dismutase), CAT (catalase), and MDA (malondialdehyde) activity. Shuttle box, rotarod, and open field results showed that crocin can substantially mitigate the deleterious effects of cisplatin on avoidance memory, explorative behavior, motor coordination, and balance. Crocin was also able to effectively avoid the negative effects of cisplatin on MDA, GPx, and CAT during the assessment of oxidative indicators, while the beneficial effect of crocin on cisplatin was not statistically significant in terms of SOD level. In conclusion, since free radicals produced by cisplatin are a contributing factor to memory loss and movement disorders, crocin, owing to its antioxidant properties, improved passive avoidance learning as well as motor activity.
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Antioxidantes , Carotenoides , Cisplatino , Ratas , Masculino , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Cisplatino/toxicidad , Ratas Wistar , Estrés Oxidativo , Superóxido Dismutasa/metabolismo , Apoyo NutricionalRESUMEN
BACKGROUND: Neurobehavioural comorbidities have a detrimental effect on the quality of life of people with epilepsy, yet tracking their impact is challenging as behaviour may vary with seizures and anti-seizure medication (ASM) side effects. Smartphones have the potential to monitor day-to-day neurobehavioural patterns objectively. We present the case of a man in his late twenties with drug-resistant focal epilepsy in whom we ascertained the effects of ASM withdrawal and a convulsive seizure on his touchscreen interactions. METHODS: Using a dedicated app, we recorded over 185 days the timestamps of 718,357 interactions. We divided the various smartphone behaviours according to the next-interval dynamics of the interactions by using a joint interval distribution (JID). During two ASM load transitions, namely before versus during tapering and tapering versus restarting medication, we used cluster-based permutation tests to compare the JIDs. We also compared the JID of the seizure day to the average of the previous 3 days. RESULTS: The cluster-based permutation tests revealed significant differences, with accelerated next-interval dynamics during tapering and a reversal upon medication restart. The day of the convulsion exhibited a marked slowing of next-interval dynamics compared to the preceding 3 days. CONCLUSION: Our findings suggest that the temporal dynamics of smartphone touchscreen interactions may help monitor neurobehavioural comorbidities in neurological care.
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Corticosteroids are essential to curative acute lymphoblastic leukemia (ALL) treatment, yet have significant neuropsychiatric side effects that decrease quality of life for patients and families. We conducted a scoping review, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, to describe the existing measurement tools used to evaluate neurobehavioral side effects of corticosteroids in pediatric ALL. From various databases and registers, 4047 studies were identified. Twenty-four articles met inclusion criteria. Clinical assessment was most used to evaluate these symptoms. Twelve validated measures were identified. Existing data about neuropsychiatric side effects of corticosteroids in pediatric ALL are extremely heterogeneous, creating challenges for standardized assessment and management.
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Corticoesteroides , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Niño , Corticoesteroides/uso terapéutico , Corticoesteroides/efectos adversos , Calidad de Vida , PronósticoRESUMEN
OBJECTIVES: The primary aim was to evaluate apathy assessment measures in relation to cognitive impairment among Hispanic/Latin Americans. METHODS: A systematic review on the relationship between apathy and cognitive impairment among Hispanic/Latin Americans across normal aging and neurocognitive disorders was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and using APA PsycInfo, Embase, and PubMed databases. Inclusion criteria required (1) a sample of English or Spanish-speaking adults ages 18 years and older, (2) with measures of apathy, (3) assessment of cognitive functioning or diagnosis of neurocognitive disorder, (4) with at least 18.5% Hispanic/Latin American represented in the sample. RESULTS: Only 14 papers met criteria to be included in this review. Of the 12 cross-sectional studies, 9 demonstrated significant associations between increased apathy and cognitive impairment, 1 demonstrated a descriptive difference between apathy and cognitive status (ie, no hypothesis test conducted), while 2 demonstrated null effects. These cross-sectional studies consisted of community and clinic samples of participants across North and South America. Two longitudinal studies conducted in North America demonstrated non-significant associations of apathy with cognitive status. CONCLUSIONS: The Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) apathy subscales were the most used measures for apathy in this review (85.7% of included studies). However, validity evidence from a review of apathy measures has warranted caution against the use of the NPI outside the context of screening for apathy. This potential measurement bias with Hispanic/Latin Americans apathy research limits conclusions drawn from the present review.
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Apatía , Disfunción Cognitiva , Humanos , Estudios Transversales , Disfunción Cognitiva/psicología , Trastornos Neurocognitivos , Hispánicos o LatinosRESUMEN
OBJECTIVE: Functional seizures are common among people with traumatic brain injury (TBI). Subjective cognitive concerns refer to a person's own perception of problems with cognitive functioning in everyday life. The authors investigated the presence and correlates of subjective cognitive concerns and the response to neurobehavioral therapy among adults with TBI and functional seizures (TBI+FS group). METHODS: In this observational study, participants in the TBI+FS group (N=47) completed a 12-session neurobehavioral therapy protocol for seizures, while participants in the comparison group (TBI without seizures) (N=50) received usual treatment. Subjective cognitive concerns, objective cognition, mental health, and quality of life were assessed before and after treatment. Data collection occurred from 2018 to 2022. RESULTS: Baseline subjective cognitive concerns were reported for 37 (79%) participants in the TBI+FS group and 20 (40%) participants in the comparison group. In a multivariable regression model in the TBI+FS group, baseline global mental health (ß=-0.97) and obsessive-compulsive symptoms (ß=-1.01) were associated with subjective cognitive concerns at baseline. The TBI+FS group had fewer subjective cognitive concerns after treatment (η2=0.09), whereas the TBI comparison group showed a nonsignificant increase in subjective cognitive concerns. CONCLUSIONS: Subjective cognitive concerns are common among people with TBI and functional seizures and may be related to general mental health and obsessive-compulsive symptoms. Evidence-based neurobehavioral therapy for functional seizures is a reasonable treatment option to address such concerns in this population, although additional studies in culturally diverse samples are needed. In addition, people with functional seizures would likely benefit from rehabilitation specifically targeted toward cognitive functioning.
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Lesiones Traumáticas del Encéfalo , Convulsiones , Humanos , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/rehabilitación , Masculino , Femenino , Adulto , Convulsiones/etiología , Convulsiones/psicología , Convulsiones/terapia , Persona de Mediana Edad , Disfunción Cognitiva/etiología , Disfunción Cognitiva/rehabilitación , Disfunción Cognitiva/terapia , Disfunción Cognitiva/fisiopatología , Calidad de Vida , Cognición/fisiología , Terapia Cognitivo-Conductual , Adulto JovenRESUMEN
OBJECTIVE: Neurobehavioral dysregulation (NBD), a core clinical feature of traumatic encephalopathy syndrome, encompasses neuropsychiatric symptoms reported among individuals with a history of repetitive head impact exposure, including contact sport athletes. The objective of this study was to examine the construct and subconstructs of NBD through a series of factor and cluster analyses. METHODS: Six clinician-scientists selected self-report questionnaire items relevant to NBD from seven available neuropsychiatric scales through a blinded voting process. These items were subjected to confirmatory factor analyses in a sample of 178 former college and professional American football players and 60 asymptomatic individuals without a history of repetitive head impact exposure. All participants were enrolled in the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Factor scores were generated on the basis of the optimal expert-informed model for NBD. Construct validity was assessed with neuropsychiatric scales not included in generation of the factor scores. Cluster analyses with NBD factor scores were used to examine symptom profiles. RESULTS: Factor analyses confirmed that NBD was composed of four subconstructs: explosivity, emotional dyscontrol, impulsivity, and affective lability. Cluster analyses indicated four distinct symptom profiles of NBD in this group of former football players: asymptomatic (N=80, 45%), short fuse (N=33, 19%), high affective lability (N=34, 19%), and high NBD (N=31, 17%). CONCLUSIONS: These findings characterize NBD as a multifaceted clinical construct with a heterogeneous presentation, providing a foundation for empirical work on the diagnostic criteria for traumatic encephalopathy syndrome and research on the neurobiological underpinnings of NBD.
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Valid clinical outcome assessments with the ability to capture meaningful aspects of neurodevelopment for individuals with neurogenetic conditions associated with profound functional impairments are lacking, yet critical for clinical care and clinical trial readiness. The purpose of this pilot study was to examine and compare the initial psychometric properties of a series of commonly used standardized and norm-referenced measures of cognition and adaptive functioning as well as alternative measures of neurobehavioral functioning designed to capture responsivity (i.e., alertness, awareness, responsivity to the environment) in those with acquired brain injuries in a sample of individuals with severe to profound functional impairment associated with a neurogenetic etiology. Ten individuals (median age = 7.5 years, IQR = 4.8-11.5, range 4-21; n = 8 male) with severe to profound functional impairment associated with SCN2A-Related Disorder and their parents were included in this study. Parents completed the Vineland Adaptive Behavior Scales, Third Edition Comprehensive Interview (Vineland-3) and the Developmental Profile, Fourth Edition Cognitive Scale (DP-4) and their children completed the Bayley Scales of Infant and Toddler Development Cognitive Scale (Bayley-4; given out of the standardized age-range) and two measures of responsivity, the Coma Recovery Scale, Pediatric and the Rappaport Coma/Near Coma Scale. Results demonstrated exceptionally low skills (median Vineland-3 Adaptive Behavior Composite = 35.5) and frequent floor effects across norm-referenced measures (i.e., Vineland-3, DP-4, Bayley-4); however, raw scores yielded more range and variability and no absolute floor effects. There were also no floor effects on measures of responsivity and findings suggest that these alternative tools may capture more variability in some aspects of neurobehavioral functioning that are critical to higher order cognitive functions, particularly for those with mental-ages below a 12 month-level. Initial evidence of construct validity of all measures in this population was shown. Findings support ongoing investigation of measures of responsivity and identified areas of potential measure modification that may improve applicability for individuals with severe to profound functional impairment associated with neurogenetic as opposed to acquired etiologies.
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PURPOSE: Motor neuron disease (MND) is a neurodegenerative disease, progressively impacting function and self-perceived quality of life (QoL). Up to 50% of people with MND can present with cognitive and behavioural impairment, with an associated increase in caregiver burden or strain. However, there has been no systematic exploration of the relationship between QoL and cognitive or behavioural impairment in MND. The aim was to determine if there is a relationship between QoL and cognitive/behavioural impairment in MND, while also supplementarily looking to determine the types of cognitive/behavioural and QoL measures utilised in these studies. METHODS: A systematic search was performed across multiple databases (PsychINFO, Embase, Medline, AMED) for research published up to the date of February 22, 2023. Studies utilising quantitative methods of measuring QoL, cognitive/behavioural functioning/impairment were included. Findings examining relationships between QoL-cognitive/behavioural impairment were extracted and synthesised. RESULTS: A total of 488 studies were identified, with 14 studies included in the systematic review. All 14 studies were observational (11 cross-sectional, 3 longitudinal). 13 studies utilised MND non-specific measures, particularly in relation to QoL and cognitive impairment. Of 8 studies measuring behavioural impairment 62.5% (N = 5) found either a lower QoL difference or association. Only 33.3% (N = 4) of 12 studies measuring cognitive impairment found a lower QoL difference or association. CONCLUSIONS: This systematic review shows that behavioural impairment may have an impact on QoL in MND. There is variability in types of assessments used to measure QoL and also cognitive/behavioural impairment, most of which are disease-non-specific. Recommendations for future research are to use comprehensive disease-specific, multidomain measures to further elucidate the QoL-cognitive/behavioural impairment relationship.
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Disfunción Cognitiva , Enfermedad de la Neurona Motora , Calidad de Vida , Humanos , Calidad de Vida/psicología , Enfermedad de la Neurona Motora/psicología , Enfermedad de la Neurona Motora/complicaciones , Disfunción Cognitiva/psicología , Disfunción Cognitiva/etiología , Cuidadores/psicología , Masculino , FemeninoRESUMEN
Intracerebral hemorrhage is a lethal cerebrovascular disease, and the inevitable secondary brain injury (SBI) is responsible for serious disability and death. Perfect therapeutic goal is to minimize SBI and restore neurobehavioral functions. Recently, neuroprotection is highlighted to reduce SBI, but it still faces "Neuronal survival but impaired functions" dilemma. Herein, this work further proposes a novel combinational therapeutic strategy of neuroprotection and neurogenesis toward this goal. However, appropriate therapeutic agents are rarely reported, and their discovery and development are urgently needed. Selenium participates in various physiological/pathological processes, which is hypothesized as a potential targeting molecule. To explore this effect, this work formulates an ultra-small selenium nanodot with a seleno-amino acid derived carbon dot domain and a hydrophilic PEG layer, surprisingly finding that it increases various selenoproteins levels at perihematomal region, to not only exert multiple neuroprotective roles at acute phase but promote neurogenesis and inhibit glial scar formation at recovery phase. At a safe dose, this combinational strategy effectively prevents SBI and recovers neurobehavioral functions to a normal level. Furthermore, its molecular mechanisms are revealed to broaden application scopes in other complex diseases.
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Lesiones Encefálicas , Accidente Cerebrovascular Hemorrágico , Fármacos Neuroprotectores , Selenio , Animales , Selenio/química , Selenio/farmacología , Selenio/uso terapéutico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/uso terapéutico , Lesiones Encefálicas/tratamiento farmacológico , Accidente Cerebrovascular Hemorrágico/tratamiento farmacológico , Neurogénesis/efectos de los fármacos , Masculino , Ratones , Selenoproteínas/metabolismo , Nanopartículas/química , Neuronas/efectos de los fármacos , Encéfalo/efectos de los fármacosRESUMEN
PURPOSE: Welders are more likely to develop neurobehavioral disorders because of their exposure to neurotoxic metals such as manganese. This study aimed to measure the neurobehavioral performance of welders occupationally exposed to manganese at welding enterprises and its relationship with the workplace environment. METHODS: It is a comparative cross-sectional study carried out on 130 welders working at 50 welding enterprises in Menoufia governorate, Egypt, compared to 130 non-occupationally exposed controls. RESULTS: It was found that the environments of the studied welding enterprises had levels of respirable dust, manganese, and total welding fumes that exceeded internationally permissible limits. In addition, the mean blood manganese levels were significantly higher among welders (4.16 ± 0.61) than the controls (1.72 ± 0.41). Welders had a significantly higher prevalence of neurological manifestations and lower performance of neurobehavioral tests. Lower neurobehavioral performance among welders was significantly correlated with increased work duration and blood levels in some tests. CONCLUSION: To lessen the fumes in the breathing zone of workers, it is therefore strongly recommended to regularly wear high-quality personal protective equipment, especially masks, and to ensure proper ventilation.
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Contaminantes Ocupacionales del Aire , Polvo , Manganeso , Exposición Profesional , Soldadura , Humanos , Egipto/epidemiología , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Estudios Transversales , Contaminantes Ocupacionales del Aire/efectos adversos , Contaminantes Ocupacionales del Aire/análisis , Manganeso/sangre , Manganeso/efectos adversos , Adulto , Masculino , Polvo/análisis , Persona de Mediana Edad , Exposición por Inhalación/efectos adversos , Exposición por Inhalación/análisis , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/sangre , Enfermedades Profesionales/inducido químicamente , Adulto JovenRESUMEN
OBJECTIVE: Considering that diagnostic decisions about mTBI are often predicated on clinical symptom criteria, it is imperative to determine which initial presentation features of mTBI have prognostic significance for identifying those at high risk for long-term functional impairment. SETTING: Zoom interview Participants: Male, former NCAA Division I, and professional-level National Football League (NFL) athletes (n = 177) between the ages of 27 and 85 (M = 54.1, SD = 14.7). DESIGN: Cross-sectional case-control. Main Measures: History of mild TBI, history of loss of consciousness (LOC), depression symptoms, insomnia, neurobehavioral symptoms. RESULTS: Number of mTBI exposures did not predict neurobehavioral symptoms (B = 0.21, SE = 0.18, p = 0.23), but number of mTBI + LOC events did (B = 2.27, SE = 0.64, p = <.001). Further analysis revealed that the number of mTBI + LOC events predicted neurobehavioral symptoms indirectly through both depression (B = 0.85, 95% CI = [0.27, 1.52) and insomnia (B = 0.81, 95% CI = [0.3, 1.4]). Further, the direct effect of mTBI + LOC events on neurobehavioral symptoms became non-significant when depression and insomnia were added to the model (B = 0.78, SE = 0.45, p = 0.08). CONCLUSIONS: Findings support LOC at time of injury as an important predictor of long-term outcomes. Additionally, results suggest depression and insomnia as potential mediators in the association between mTBI + LOC and neurobehavioral symptoms. These findings provide justification for early depression and insomnia symptom monitoring following mTBI + LOC.
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Atletas , Depresión , Fútbol Americano , Trastornos del Inicio y del Mantenimiento del Sueño , Inconsciencia , Humanos , Masculino , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Fútbol Americano/lesiones , Adulto , Atletas/psicología , Estudios Transversales , Persona de Mediana Edad , Depresión/etiología , Estudios de Casos y Controles , Anciano , Inconsciencia/etiología , Anciano de 80 o más Años , Traumatismos en Atletas/complicaciones , Traumatismos en Atletas/psicología , Conmoción Encefálica/complicaciones , Conmoción Encefálica/psicología , Conmoción Encefálica/diagnóstico , UniversidadesRESUMEN
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.
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Proteínas de la Membrana , Nitrilos , Piretrinas , Femenino , Humanos , Embarazo , Ratas , Hipocampo/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/efectos de los fármacos , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Proteínas de la Membrana/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Nitrilos/toxicidad , Piretrinas/toxicidad , Canal Aniónico 1 Dependiente del Voltaje/efectos de los fármacos , Canal Aniónico 1 Dependiente del Voltaje/metabolismo , AnimalesRESUMEN
Methylmercury (MeHg), a potent neurotoxic substance, causes adverse health outcomes by modulating metabolites through altered gut microbiota patterns. Among the many metabolites, neurotransmitters play a particularly important role in the nervous system and behavior. Resveratrol (RSV) has been investigated as an antiaging, antioxidant, anti-inflammatory, and neuroprotective agent. The current study evaluated that RSV is protective of neurodevelopmental toxicity induced by MeHg and further explored the underlying mechanisms. Sprague-Dawley rats were treated with 1.2 mg/kg/d of MeHg, and the effects were evaluated after supplementation with RSV (20 mg/kg/d). The results indicated that MeHg had adverse effects on early neurodevelopmental indicators in the experimental group offspring as compared to control pups. Interestingly, RSV significantly improved the MeHg-induced delays in the neurobehavioral reflexes and reduced the total mercury (THg) concentration in the colons of the offspring rats. In agreement, RSV administration improved the gut microbiota diversity and structure by increasing the abundance of probiotics and upregulating the expression of tight junction proteins. It also ameliorated the MeHg-induced abnormalities in the expression profiles of neurotransmitters. Furthermore, eight key bacteria that were strongly linked with the neurotransmitters and neuroreflex parameters were identified. Taken together, these results demonstrate that RSV treatment effectively reduces the occurrence of neurodevelopmental toxicity caused by perinatal MeHg exposure by modulating the intestinal flora and neurotransmitter metabolism. These findings provide a new therapeutic approach for treating MeHg-induced neurotoxicity. The cover image is based on the Research Article Resveratrol alleviates perinatal methylmercury-induced neurobehavioral impairments by modulating the gut microbiota composition and neurotransmitter disturbances by Fang Chen et al., https://doi.org/10.1002/tox.23973.
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Microbioma Gastrointestinal , Compuestos de Metilmercurio , Embarazo , Femenino , Ratas , Animales , Compuestos de Metilmercurio/toxicidad , Microbioma Gastrointestinal/fisiología , Resveratrol/farmacología , Resveratrol/uso terapéutico , Ratas Sprague-Dawley , NeurotransmisoresRESUMEN
Military personnel, firefighters, and fire survivors exhibit a higher prevalence of mental health conditions such as depression and post-traumatic stress disorder (PTSD) compared to the general population. While numerous studies have examined the neurological impacts of physical trauma and psychological stress, research on acute neurobehavioral effects of gas inhalation from explosions or fires is limited. This study investigates the early-stage neurobehavioral and neuronal consequences of acute explosion gas inhalation in Sprague-Dawley rats. Rats were exposed to simulated explosive gas and subsequently assessed using behavioral tests and neurobiological analyses. The high-dose exposure group demonstrated significant depression-like behaviors, including reduced mobility and exploration. However, neuronal damage was not evident in histological analyses. Immunofluorescence revealed increased density of radial glia and oligodendrocytes in specific brain regions, suggesting hypoxia and axon damage induced by gas inhalation as a potential mechanism for the observed neurobehavioral changes. These findings underscore the acute impact of explosion gas inhalation on mental health, highlighting the habenula and dentate gyrus of hippocampus as the possible target regions. The findings are expected to support early diagnosis and treatment strategies for brain injuries caused by explosion gas, offering insights into early intervention for depression and PTSD in affected populations.
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Conducta Animal , Explosiones , Neuroglía , Ratas Sprague-Dawley , Animales , Masculino , Ratas , Neuroglía/efectos de los fármacos , Neuroglía/patología , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Exposición por Inhalación/efectos adversos , Gases/toxicidad , Depresión/inducido químicamenteRESUMEN
This study evaluated criteria for neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). Kable et al. (Child Psychiatry Hum Dev 55:426, 2022) assessed the validity of this diagnosis in a sample with low exposure to alcohol. The current study expanded this assessment to a sample with a wider age range and heavier alcohol exposure. Data were collected from participants (5-17 years) with prenatal alcohol exposure (PAE) and typically developing controls at six Collaborative Initiative on Fetal Alcohol Spectrum Disorders sites using neuropsychological assessment and caregiver reports. Impairment was tested at 1SD, 1.5SD, and 2SD below the normative average and a modification of the adaptive functioning requirement was tested. Testing impairment at 1SD resulted in the highest endorsement rates in both groups. Our findings replicated the study by Kable et al. and show that current criteria captured a high rate of those with PAE and that requiring fewer adaptive functioning criteria resulted in higher sensitivity to PAE.
RESUMEN
Indoor temperature has a critical impact on the performance of office workers. This study aimed to evaluate the effect of indoor temperature on work performance through subjective assessments, neurobehavioral tests, and physiological measurements. The experiment was conducted in a controlled office environment. Under each temperature condition, participants voted on their perception of thermal sensation, thermal satisfaction, and sick building syndrome (SBS) symptoms. Participants were given neurobehavioral tests based on a ten-item task, and their body temperature, blood pressure, heart rate, and blood oxygen saturation were measured before and after the tests. The study showed that the effect of indoor temperature on the test tasks varied greatly and depended on the task type. The indoor temperature, thermal sensation votes, and body temperature for optimum work performance were 17 °C, -0.57, and 36.4 °C, respectively. Work performance was positively correlated with thermal satisfaction votes and negatively correlated with sleepiness intensity.Practitioner summary: Work performance is closely related to indoor temperature. This study evaluated the effect of indoor temperature on work performance through subjective assessments, neurobehavioral tests, and physiological measurements. The relationships between work performance and indoor temperature, perceived votes, and physiological parameters were established, respectively.