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Cell Aug 2020The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains...
The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69 CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems. VIDEO ABSTRACT.
Topics: Adult; Animals; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Behavior Rating Scale; Blood Cells; Brain; CD4-Positive T-Lymphocytes; Child; Female; Fetus; Humans; Lectins, C-Type; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; Middle Aged; Neurogenesis; Parabiosis; Pyramidal Cells; Single-Cell Analysis; Spleen; Synapses; Transcriptome
PubMed: 32702313
DOI: 10.1016/j.cell.2020.06.026 -
American Family Physician Nov 2020Attention-deficit/hyperactivity disorder (ADHD) is a multidimensional chronic neurodevelopmental condition that affects 8.4% of U.S. children between two and 17 years of...
Attention-deficit/hyperactivity disorder (ADHD) is a multidimensional chronic neurodevelopmental condition that affects 8.4% of U.S. children between two and 17 years of age and may pose long-term morbidity if untreated. The evaluation for ADHD begins when parents or caregivers present to primary care physicians with concerns about behavior problems or poor school or social function. A comprehensive history and physical examination should assess for comorbid or other conditions that can mimic ADHD. The combination of Diagnostic and Statistical Manual of Mental Disorders, 5th ed., criteria and validated screening tools completed by parents, teachers, or other adults can aid in establishing the diagnosis. The goals of treatment include symptom reduction and improved social and cognitive function. Psychosocial interventions are the recommended first-line treatment for preschool children (four to five years) and can improve overall function when used as an adjunct therapy in elementary school children (six to 11 years of age) and adolescents (12 to 17 years of age). Stimulant medications are well-established as an effective treatment for reducing symptoms of ADHD in elementary school children and adolescents. Nonstimulant medications are less effective but reasonable as adjunct or alternative therapy when stimulants are ineffective or not tolerated. Regular follow-up is key in the management of ADHD and should assess symptoms, overall function, presence of comorbidities, adverse effects of treatment, and medication use.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Behavior Rating Scale; Central Nervous System Stimulants; Checklist; Child; Child Behavior; Child, Preschool; Diagnostic and Statistical Manual of Mental Disorders; Humans; Parents; Psychosocial Intervention; School Teachers
PubMed: 33179887
DOI: No ID Found -
PloS One 2017The chronic unpredictable mild stress model of depression has been widely used as an experimental tool to investigate human psychopathology. Our objective was to provide...
The chronic unpredictable mild stress model of depression has been widely used as an experimental tool to investigate human psychopathology. Our objective was to provide an update on the validity and reliability of the chronic unpredictable mild stress model, by analyzing the interrelationships among the indexes using stepwise discriminant analysis and Pearson correlation coefficient to examine the possible combinations. We evaluated the depressive rats in both the presence and the absence of chronic unpredictable mild stress, using weight change, percentage of sucrose preference, coat state, splash test, open-field test, elevated plus-maze test, forced swimming test, and Morris water maze test. The results showed that 6-week-long chronic unpredictable mild stress produces significant depression and anxiety-like behavior. The combination of body weight change, percentage of sucrose preference, coat state score, open-field score, grooming latency of splash test, immobility time in force swimming test, and platform crossing in the Morris water maze test can effectively discriminate between normal and chronic unpredictable mild stress rats. Strong interrelationships were noted among these indexes in both open-field test and elevated plus-maze test. In conclusion, there might be certain criteria for the combination of behavioral endpoints, which is advantageous to more effectively and reliably assess the chronic unpredictable mild stress induced depression model.
Topics: Animals; Behavior Rating Scale; Behavior, Animal; Body Weight; Depression; Discriminant Analysis; Disease Models, Animal; Male; Maze Learning; Rats, Sprague-Dawley; Reproducibility of Results; Stress, Psychological; Sucrose; Swimming
PubMed: 28931086
DOI: 10.1371/journal.pone.0185129 -
Clinical and Experimental Dental... Oct 2021Dental anxiety distresses children and their families with consequent poor oral health and costly pediatric dental services. Children's behaviors could be modified using... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Dental anxiety distresses children and their families with consequent poor oral health and costly pediatric dental services. Children's behaviors could be modified using a distraction technique for improved dental treatment. The study evaluates the effects of an audio-visual distraction on children's behaviors and pain expressions during dental treatment.
MATERIAL AND METHODS
One hundred healthy children, between 4 and 6 years of age, were randomly assigned to one of two groups: audio visual distraction (AVD, N = 61) group and control (CTR, N = 39) group. The pre and post pain expression was collected using a faces pain rating scale from the participated children. Children's behavior was evaluated using the Frankl behavior rating scale by the assigned dentist. Data was analyzed using chi-squared tests and analysis of variance.
RESULTS
The AVD group demonstrated more "definitely positive" behavior (91.8%) compared to the CTR group (35.9%) based on the Frankl scale evaluation from pre- and post-treatment (p < 0.0001). The pain rating scale did not demonstrate a significant difference in post-treatment pain scales (p = 0.2073) or changes in pain (p = 0.1532) between the AVD group and CTR group.
CONCLUSIONS
The AVD is an effective distraction tool for young children during dental treatment regardless of child's subjective pain expression.
Topics: Child; Child Behavior; Child, Preschool; Humans; Pain; Pain Measurement
PubMed: 33622030
DOI: 10.1002/cre2.407 -
International Journal of Molecular... Feb 2020Plastic pollution is a growing global emergency and it could serve as a geological indicator of the Anthropocene era. Microplastics are potentially more hazardous than...
Nanoplastics Cause Neurobehavioral Impairments, Reproductive and Oxidative Damages, and Biomarker Responses in Zebrafish: Throwing up Alarms of Wide Spread Health Risk of Exposure.
Plastic pollution is a growing global emergency and it could serve as a geological indicator of the Anthropocene era. Microplastics are potentially more hazardous than macroplastics, as the former can permeate biological membranes. The toxicity of microplastic exposure on humans and aquatic organisms has been documented, but the toxicity and behavioral changes of nanoplastics (NPs) in mammals are scarce. In spite of their small size, nanoplastics have an enormous surface area, which bears the potential to bind even bigger amounts of toxic compounds in comparison to microplastics. Here, we used polystyrene nanoplastics (PS-NPs) (diameter size at ~70 nm) to investigate the neurobehavioral alterations, tissue distribution, accumulation, and specific health risk of nanoplastics in adult zebrafish. The results demonstrated that PS-NPs accumulated in gonads, intestine, liver, and brain with a tissue distribution pattern that was greatly dependent on the size and shape of the NPs particle. Importantly, an analysis of multiple behavior endpoints and different biochemical biomarkers evidenced that PS-NPs exposure induced disturbance of lipid and energy metabolism as well as oxidative stress and tissue accumulation. Pronounced behavior alterations in their locomotion activity, aggressiveness, shoal formation, and predator avoidance behavior were exhibited by the high concentration of the PS-NPs group, along with the dysregulated circadian rhythm locomotion activity after its chronic exposure. Moreover, several important neurotransmitter biomarkers for neurotoxicity investigation were significantly altered after one week of PS-NPs exposure and these significant changes may indicate the potential toxicity from PS-NPs exposure. In addition, after ~1-month incubation, the fluorescence spectroscopy results revealed the accumulation and distribution of PS-NPs across zebrafish tissues, especially in gonads, which would possibly further affect fish reproductive function. Overall, our results provided new evidence for the adverse consequences of PS-NPs-induced behavioral dysregulation and changes at the molecular level that eventually reduce the survival fitness of zebrafish in the ecosystem.
Topics: Aggression; Animals; Behavior Rating Scale; Behavior, Animal; Biomarkers; Brain; Circadian Rhythm; Ecosystem; Energy Metabolism; Gonads; Intestines; Lipid Metabolism; Liver; Microscopy, Electron, Transmission; Muscles; Nanoparticles; Neurotransmitter Agents; Oxidative Stress; Polystyrenes; Risk Assessment; Spectrometry, Fluorescence; Tissue Distribution; Water Pollution; Zebrafish
PubMed: 32093039
DOI: 10.3390/ijms21041410 -
Globalization and Health Apr 2021To explore the influences of digital media use on the core symptoms, emotional state, life events, learning motivation, executive function (EF) and family environment of...
OBJECTIVE
To explore the influences of digital media use on the core symptoms, emotional state, life events, learning motivation, executive function (EF) and family environment of children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) during the novel coronavirus disease 2019 (COVID-19) pandemic.
METHOD
A total of 192 participants aged 8-16 years who met the diagnostic criteria for ADHD were included in the study. Children scoring higher than predetermined cut-off point in self-rating questionnaires for problematic mobile phone use (SQPMPU) or Young's internet addiction test (IAT), were defined as ADHD with problematic digital media use (PDMU), otherwise were defined as ADHD without PDMU. The differences between the two groups in ADHD symptoms, EF, anxiety and depression, stress from life events, learning motivation and family environment were compared respectively.
RESULTS
When compared with ADHD group without PDMU, the group with PDMU showed significant worse symptoms of inattention, oppositional defiant, behavior and emotional problems by Swanson, Nolan, and Pelham Rating Scale (SNAP), more self-reported anxiety by screening child anxiety-related emotional disorders (SCARED) and depression by depression self-rating scale for children (DSRSC), more severe EF deficits by behavior rating scale of executive function (BRIEF), more stress from life events by adolescent self-rating life events checklist (ASLEC), lower learning motivation by students learning motivation scale (SLMS), and more impairment on cohesion by Chinese version of family environment scale (FES-CV). The ADHD with PDMU group spent significantly more time on both video game and social media with significantly less time spend on physical exercise as compared to the ADHD without PDMU group.
CONCLUSION
The ADHD children with PDMU suffered from more severe core symptoms, negative emotions, EF deficits, damage on family environment, pressure from life events, and a lower motivation to learn. Supervision of digital media usage, especially video game and social media, along with increased physical exercise, is essential to the management of core symptoms and associated problems encountered with ADHD.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; COVID-19; Child; China; Female; Humans; Internet; Internet Addiction Disorder; Male; Surveys and Questionnaires
PubMed: 33874977
DOI: 10.1186/s12992-021-00699-z -
Journal of Neuroinflammation Jul 2021Germinal matrix hemorrhage (GMH) is defined by the rupture of immature blood vessels in the germinal matrix, where subsequent hemorrhage enters the subependymal zone and...
BACKGROUND
Germinal matrix hemorrhage (GMH) is defined by the rupture of immature blood vessels in the germinal matrix, where subsequent hemorrhage enters the subependymal zone and the cerebral lateral ventricles. The consequent blood clot has been identified as the causative factor of secondary brain injury, which triggers a series of complex parallel and sequential harmful mechanisms, including neuroinflammation. The orphan G-protein-coupled receptor 40 (GPR40), a free fatty acid (FFA) receptor 1, has been shown to exert anti-inflammatory effects when activated and improved outcomes in animal models of stroke. We aimed to investigate the anti-inflammatory effects of GPR40 and its underlying mechanisms after GMH.
METHODS
GMH model was induced in 7-day-old rat pups by an intraparenchymal injection of bacterial collagenase. GPR40 agonist, GW9508, was administered intranasally 1 h, 25 h, and 49 h after GMH induction. CRISPR targeting GPR40, PAK4, and KDM6B were administered through intracerebroventricular injection 48 h before GMH induction. Neurologic scores, microglia polarization, and brain morphology were evaluated by negative geotaxis, right reflex, rotarod test, foot fault test, Morris water maze, immunofluorescence staining, Western blots, and nissl staining respectfully.
RESULTS
The results demonstrated that GW9508 improved neurological and morphological outcomes after GMH in the short (24 h, 48 h, 72h) and long-term (days 21-27). However, the neuroprotective effects of treatment were abolished by GW1100, a selective GPR40 antagonist. GW9508 treatment increased populations of M2 microglia and decreased M1 microglia in periventricular areas 24 h after GMH induction. GW9508 upregulated the phosphorylation of PAK4, CREB, and protein level of KDM6B, CD206, IL-10, which was also met with the downregulation of inflammatory markers IL-1β and TNF-α. The mechanism study demonstrated that the knockdown of GPR40, PAK4, and KDM6B reversed the neuroprotective effects brought on by GW9508. This evidence suggests that GPR40/PAK4/CREB/KDM6B signaling pathway in microglia plays a role in the attenuation of neuroinflammation after GMH.
CONCLUSIONS
In conclusion, the present study demonstrates that the activation of GPR40 attenuated GMH-induced neuroinflammation through the activation of the PAK4/CREB/KDM6B signaling pathway, and M2 microglia may be a major mediator of this effect. Thus, GPR40 may serve as a potential target in the reduction of the inflammatory response following GMH, thereby improving neurological outcomes in the short- and long-term.
Topics: Animals; Animals, Newborn; Behavior Rating Scale; Cerebral Hemorrhage; Cytokines; Disease Models, Animal; Fluorescent Antibody Technique; Jumonji Domain-Containing Histone Demethylases; Microglia; Neuroinflammatory Diseases; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 34275493
DOI: 10.1186/s12974-021-02209-9 -
Dialogues in Clinical Neuroscience Sep 2019New psychopharmacological treatments are needed for affective and nonaffective psychoses, especially for the associated negative and cognitive symptoms. Earlier... (Review)
Review
New psychopharmacological treatments are needed for affective and nonaffective psychoses, especially for the associated negative and cognitive symptoms. Earlier developments mostly failed, probably partly because of limitations in behavioral models used for validation. Now, deeper understanding of the genetics underlying disease pathogenesis and progress in genetic engineering will generate many rodent models with increased construct validity. To improve these models' translational value, we need complementary data from nonhuman primates. We also have to improve and streamline behavioral test systems to cope with increased demand. Here, we propose a comprehensive neurocognitive test battery that should overcome the disadvantages of single tests and yield cognitive/behavioral profiles for modeling subsets of patient symptoms. Further, we delineate a concept for classifying disease-relevant cognitive endophenotypes to balance between face and construct validity and clinical diagnostics. In summary, this review discusses new concepts and the limitations and future potential of translational research on cognition in psychiatry. .
Topics: Animals; Behavior Rating Scale; Cognition; Humans; Memory; Models, Animal; Primates; Rodentia; Translational Research, Biomedical
PubMed: 31749649
DOI: 10.31887/DCNS.2019.21.3/mrossner -
Acta Dermato-venereologica Sep 2012The most commonly used tool for self-report of pruritus intensity is the visual analogue scale (VAS). Similar tools are the numerical rating scale (NRS) and verbal... (Comparative Study)
Comparative Study
Assessment of pruritus intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus.
The most commonly used tool for self-report of pruritus intensity is the visual analogue scale (VAS). Similar tools are the numerical rating scale (NRS) and verbal rating scale (VRS). In the present study, initiated by the International Forum for the Study of Itch assessing reliability of these tools, 471 randomly selected patients with chronic itch (200 males, 271 females, mean age 58.44 years) recorded their pruritus intensity on VAS (100-mm line), NRS (0-10) and VRS (four-point) scales. Re-test reliability was analysed in a subgroup of 250 patients after one hour. Statistical analysis showed a high reliability and concurrent validity (r>0.8; p<0.01) for all tools. Mean values of all scales showed a high correlation. In conclusion, high reliability and concurrent validity was found for VAS, NRS and VRS. On re-test, higher correlation and less missing values were observed. A training session before starting a clinical trial is recommended.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chronic Disease; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Pruritus; Reproducibility of Results; Severity of Illness Index; Surveys and Questionnaires; Verbal Behavior; Young Adult
PubMed: 22170091
DOI: 10.2340/00015555-1246 -
Brain Sciences May 2022Olfactory dysfunction is considered a pre-cognitive biomarker of Alzheimer's disease (AD). Because the olfactory system is highly conserved across species, mouse models... (Review)
Review
Olfactory dysfunction is considered a pre-cognitive biomarker of Alzheimer's disease (AD). Because the olfactory system is highly conserved across species, mouse models corresponding to various AD etiologies have been bred and used in numerous studies on olfactory disorders. The olfactory behavior test is a method required for early olfactory dysfunction detection in AD model mice. Here, we review the olfactory evaluation of AD model mice, focusing on traditional olfactory detection methods, olfactory behavior involving the olfactory cortex, and the results of olfactory behavior in AD model mice, aiming to provide some inspiration for further development of olfactory detection methods in AD model mice.
PubMed: 35624994
DOI: 10.3390/brainsci12050607