Voltage-clamp fluorometry for advancing mechanistic understanding of ion channel mechanisms with a focus on acid-sensing ion channels.

Voltage-clamp fluorometry (VCF) has revolutionized the study of ion channels by combining electrophysiology with fluorescence spectroscopy. VCF allows ion channel researchers to link dynamic structural changes, measured in real time, to function. Acid-sensing ion channels (ASICs) are Na+-permeable non-voltage-gated ion channels of the central and peripheral nervous system. They function as pH sensors, triggering neuronal excitation when pH decreases. Animal studies have shown the importance of ASICs for pain and fear sensation, learning, and neurodegeneration following ischaemic stroke. This review explores the technical bases and various developments of VCF, including fluorescence resonance energy transfer and the use of unnatural fluorescent amino acids. We provide an overview of VCF applications with a focus on ASICs, detailing how VCF has unveiled proton-induced conformational changes in key regions such as the acid pocket, wrist, and pore, crucial for understanding transitions between closed, open, and desensitized states.

Neuron-restrictive silencer factor/repressor element 1-silencing transcription factor (NRSF/REST) controls spatial K+ buffering in primary cortical astrocytes.

Neuron-restrictive silencer factor/repressor element 1 (RE1)-silencing transcription factor (NRSF/REST) is a transcriptional repressor of a large cluster of neural genes containing RE1 motifs in their promoter region. NRSF/REST is ubiquitously expressed in non-neuronal cells, including astrocytes, while it is down-regulated during neuronal differentiation. While neuronal NRSF/REST homeostatically regulates intrinsic excitability and synaptic transmission, the role of the high NRSF/REST expression levels in the homeostatic functions of astrocytes is poorly understood. Here, we investigated the functional consequences of NRSF/REST deletion in primary cortical astrocytes derived from NRSF/REST conditional knockout mice (KO). We found that NRSF/REST KO astrocyte displayed a markedly reduced activity of inward rectifying K+ channels subtype 4.1 (Kir4.1) underlying spatial K+ buffering that was associated with a decreased expression and activity of the glutamate transporter-1 (GLT-1) responsible for glutamate uptake by astrocytes. The effects of the impaired astrocyte homeostatic functions on neuronal activity were investigated by co-culturing wild-type hippocampal neurons with NRSF/REST KO astrocytes. Interestingly, neurons experienced increased neuronal excitability at high firing rates associated with decrease after hyperpolarization and increased amplitude of excitatory postsynaptic currents. The data indicate that astrocytic NRSF/REST directly participates in neural circuit homeostasis by regulating intrinsic excitability and excitatory transmission and that dysfunctions of NRSF/REST expression in astrocytes may contribute to the pathogenesis of neurological disorders.

Exploring emotion dysregulation in adolescence and its association with social immaturity, self-representation, and thought process problems.

Background and aims: This study aimed to explore the complex phenomenon of emotional dysregulation, particularly in adolescence, which is associated with many mental health disorders and problems. Increasing the knowledge of clinicians and researchers in this area can be helpful in guiding future treatment plans. The aim of the study was to investigate, from an exploratory perspective, which structural aspects of adolescent functioning (assessed using the Rorschach test and administered and scored according to the Comprehensive System, CS, by Exner) were associated with different dimensions of emotional dysregulation (evaluated using the Difficulties in Emotion Dysregulation Scale, DERS). Method: Secondary data were used for the study, which included 100 adolescents, with 50 in the clinical group (patients with complex trauma histories residing in therapeutic and socio-rehabilitative communities) and 50 in the nonclinical group (recruited from a scout group and middle and high schools). The two groups were compared on terms of the mean scores obtained in the DERS scales (one-tailed t-test) and the proportions of cases that obtained pathological values for selected Rorschach CS indicators (z-test). Partial correlations were calculated between the DERS scales and the Rorschach CS variables to explore which structural dimensions of functioning were associated with different characteristics of emotional dysregulation. Results: The results indicated that the two groups differed in their outcomes on all DERS scales, except for Awareness and Goals, and on four Rorschach CS variables (EgoIndex, a:p, Wsum6, and MOR). Some significant positive and negative correlations between the Rorschach CS variables and the DERS scales also emerged. Conclusion: These results suggest that the dimensions of functioning associated with emotional dysregulation are related to self-representation, relational immaturity, and thought processes character and characterize membership in a therapeutic community. The correlations described in the article warrants further consideration. Finally, the study's limitations and future research prospects are presented.

Can Dissociation Mediate the Relationship between Emotional Dysregulation and Intelligence? An Empirical Study Involving Adolescents with and without Complex Trauma Histories.

The main aim of the study was to map the psychological functioning of individuals with adverse childhood experiences, with the objective to characterize developmental trajectories. Specifically, we investigated the relations among three of the seven domains of impairment in children and adolescents who had been exposed to complex trauma. To this end, we tested a mediation model with emotional dysregulation as the independent variable, intelligence as the dependent variable, and dissociation as the mediator. The research sample was composed of 64 participants (10-19 years old); 31 adolescents formed the clinical group and 33 the non-clinical group; for the clinical group, we recruited adolescents who were residents of therapeutic communities and had a history of complex trauma. Both groups completed the Difficulties in emotion regulation scale (DERS), Adolescent dissociative experience scale (A-DES), Trauma symptom checklist for children (TSCC), and Wechsler scales. The data analysis yielded significant results for the control group only. We suggest that healthy adolescents adopt a non-pathological dissociative cognitive style in response to increased emotional dysregulation, thus explaining their enhanced cognitive performance.

The Well-Being of Social Health Professionals: Relationship between Coping Strategies, Emotional Regulation, Metacognition and Quality of Professional Life.

Social health professionals should have the knowledge and skills and use personal resources that promote the helping relationship, access to effective intervention strategies, and well-being at work. This study aims to investigate the relationship between some personal resources (coping strategies, emotional regulation and metacognition) and professional satisfaction in a group of social-health professionals working with minors suffering from psychosocial distress. In this professional group, the risk of burnout is common and the quality of professional life is strongly related to the intensity and frequency of exposure to critical and traumatic events. The sample was assessed using self-report instruments: Professional Quality of Life Scale, Coping Orientation to the Problem Experienced, Difficulties in Emotional Regulation Scale and Metacognition Self-Assessment Scale. The quality of professional life showed significant correlations with the psychological characteristics studied. We then tested different regression models: coping orientation scores were found to be a significant predictor of quality of work life for all three components, while emotional dysregulation scores appeared to predict only the burnout component. The quality of professional life of social health professionals was influenced by individual resources at different levels, regardless of knowledge and skills. They showed greater fatigue and aspects of secondary traumatization when emotional disengagement occurred and it seemed to be difficult for them to accept their emotional reactions.

Burnout Syndrome and COVID-19 Lockdown: Research on Residential Care Workers Who Assume Parental Roles with Youths.

Healthcare professionals are at higher risk of developing and experiencing burnout. Parents may also suffer from prolonged stressful conditions that lead to physical and emotional exhaustion. Residential youth care workers assume a caregiving role that can lead to persistent stressful conditions that affect their relationship with the youth. In addition, the COVID-19 lockdown has had a negative impact on both the organization and the work, as well as on the lifestyle of workers and minors. In fact, during the pandemic, contact with families was not possible due to restrictions and this increased the need for caregivers to assume a parental role. This research aims to examine the risk of burnout in a sample of 75 healthcare professionals working with youths and the association with psychological traits. Then, we aim to evaluate these aspects during the COVID-19 lockdown The measurements, conducted in both February 2019 and April 2021, included six questionnaires: MBI to assess burnout, TAS_20 to explore alexithymic traits, COPE_NVI to assess coping strategies, FDS_R to quantify frustration intolerance at work, IRI for empathy, and FFMQ to investigate awareness and emotional regulation. Our sample shows a medium-high risk of developing burnout, which worsened during the pandemic. A worsening of emotional skills, paralleled by a greater empathic investment required by the emergency situation, and an assumed parental role is observable. Coping strategies correlate with burnout risk, as avoidance strategies were strongly associated with emotional exhaustion. These findings suggest an urgent need to develop targeted and timely interventions for healthcare professionals in order to prevent long-term consequences.