Mental health in the United States during the COVID-19 pandemic: A longitudinal examination of the ameliorating effect of meaning salience.

During the COVID-19 pandemic, various restrictions forced people around the world to socially isolate. People were asked to stay at home and were largely unable to do many of the activities that they derived meaning from. Since meaning is often related to mental health, these restrictions were likely to decrease mental health. The current study aimed to examine these effects and additionally benefit individuals' mental health by making their meaning salient. Specifically, the goal of the research was to design an intervention that could counter the potential negative effects of social distancing. We recruited a total of 96 U.S.A. residents (M age = 34.45, 92.7% Female) and assigned them to either the control group or to a meaning salience intervention. That is, participants either focused on the meaning of their daily activities (n = 45) or did not participate in any study-related activities during the week (n = 51). They completed various measures of mental health before and after this experimental period. Results suggested that the control group reported significantly greater anxiety, depression, and stress at the end of the week. In contrast, the experimental group reported less anxiety and trended toward less depression and stress at the end of that same week. In all, results suggest that simply focusing on one's daily activities and the meaning found in them protected people from the otherwise detrimental effects of the restrictions. This provides a promising and simple intervention that may assist both individuals and practitioners aiming to improve mental health, especially in challenging times.

Meaning gained versus meaning lost: The effects of meaning salience on anxiety and depression during the coronavirus pandemic.

People who have meaningful lives generally experience less anxiety and depression. Meaning salience, or the awareness of the meaning in one's life, is believed to partially explain this relationship. However, in times of isolation, what might be most salient to people are the meaningful aspects of their lives that have disappeared. This study seeks to understand how making gained versus lost meaning salient affects anxiety and depression. Participants either wrote for 5 minutes about how their life gained meaning (n = 29) or lost meaning (n = 30) due to the coronavirus restrictions, or about music (i.e., the control condition; n = 32). Those who wrote about gained meaning experienced less momentary anxiety than those who wrote about lost meaning. In addition, meaning salience moderated the relationship between meaning and both anxiety and depression. Those who wrote about gained meaning appeared to exhibit a positive relationship between meaning in life (MIL) and both anxiety and depression, while those who wrote about lost meaning exhibited negative relationships. In all, this suggests that meaning salience is not always positive and that researchers and practitioners should consider how making positive meaning salient may be more beneficial than a general focus on MIL.

Metabolomic profiling identifies distinct phenotypes for ASS1 positive and negative GBM.

BACKGROUND: Tumour cells have a high demand for arginine. However, a subset of glioblastomas has a defect in the arginine biosynthetic pathway due to epigenetic silencing of the rate limiting enzyme argininosuccinate synthetase (ASS1). These tumours are auxotrophic for arginine and susceptible to the arginine degrading enzyme, pegylated arginine deiminase (ADI-PEG20). Moreover, ASS1 deficient GBM have a worse prognosis compared to ASS1 positive tumours. Since altered tumour metabolism is one of the hallmarks of cancer we were interested to determine if these two subtypes exhibited different metabolic profiles that could allow for their non-invasive detection as well as unveil additional novel therapeutic opportunities. METHODS: We looked for basal metabolic differences using one and two-dimensional gas chromatography-time-of-flight mass spectrometry (1D/2D GC-TOFMS) followed by targeted analysis of 29 amino acids using liquid chromatography-time-of-flight mass spectrometry (LC-TOFMS). We also looked for differences upon arginine deprivation in a single ASS1 negative and positive cell line (SNB19 and U87 respectively). The acquired data was evaluated by chemometric based bioinformatic methods. RESULTS: Orthogonal partial least squares-discriminant analysis (OPLS-DA) of both the 1D and 2D GC-TOFMS data revealed significant systematic difference in metabolites between the two subgroups with ASS1 positive cells generally exhibiting an overall elevation of identified metabolites, including those involved in the arginine biosynthetic pathway. Pathway and network analysis of the metabolite profile show that ASS1 negative cells have altered arginine and citrulline metabolism as well as altered amino acid metabolism. As expected, we observed significant metabolite perturbations in ASS negative cells in response to ADI-PEG20 treatment. CONCLUSIONS: This study has highlighted significant differences in the metabolome of ASS1 negative and positive GBM which warrants further study to determine their diagnostic and therapeutic potential for the treatment of this devastating disease.

Correction to: Metabolomic profiling identifies distinct phenotypes for ASS1 positive and negative GBM.

In the original publication of this article [1], published on 8 February 2018, it was noticed that the acknowledgement of the source of the drug ADI-PEG20 was missing.

Social anxiety and eating disorder comorbidity and underlying vulnerabilities: Using network analysis to conceptualize comorbidity.

OBJECTIVE: Eating disorders (EDs) and social anxiety disorder (SAD) are highly co-occurring. This comorbidity is extremely relevant, given that individuals with comorbid ED-SAD are less likely to seek and/or benefit from ED treatment. METHOD: We used network analysis to conceptualize ED-SAD comorbidity in a sample of 2,215 participants with a primary diagnosis of ED, SAD, or no known diagnosis. We used novel network analyses methods to select symptoms for our models, identify potential illness pathways (i.e., bridge symptoms) between disorders and underlying vulnerabilities (e.g., perfectionism, social appearance anxiety), and to compare across sample types (e.g., clinical vs. nonclinical). We also tested several novel network analyses methods aimed at the following methodological concerns: (a) topological concerns (i.e., which items should be included in NA models), (b) how to use empirical indices to quantify bridge symptoms and (c) what differences in networks across samples mean. RESULTS: We found that difficulty with drinking beverages and eating in public were bridge symptoms between ED and SAD. We also found that feeling nervous about one's appearance was a bridge symptom. CONCLUSIONS: We identified public eating and drinking as bridge symptoms between EDs and SAD. Future research is needed to test if interventions focused on public eating and drinking might decrease symptoms of both EDs and SAD. Researchers can use this study (code provided) as an exemplar for how to use network analysis, as well as to use network analysis to conceptualize ED comorbidity and compare network structure and density across samples.

Rapid sodium signaling couples glutamate uptake to breakdown of ATP in perivascular astrocyte endfeet.

Perivascular endfeet of astrocytes are highly polarized compartments that ensheath blood vessels and contribute to the blood-brain barrier. They experience calcium transients with neuronal activity, a phenomenon involved in neurovascular coupling. Endfeet also mediate the uptake of glucose from the blood, a process stimulated in active brain regions. Here, we demonstrate in mouse hippocampal tissue slices that endfeet undergo sodium signaling upon stimulation of glutamatergic synaptic activity. Glutamate-induced endfeet sodium transients were diminished by TFB-TBOA, suggesting that they were generated by sodium-dependent glutamate uptake. With local agonist application, they could be restricted to endfeet and immunohistochemical analysis revealed prominent expression of glutamate transporters GLAST and GLT-1 localized towards the neuropil vs. the vascular side of endfeet. Endfeet sodium signals spread at an apparent maximum velocity of ∼120 µm/s and directly propagated from stimulated into neighboring endfeet; this spread was omitted in Cx30/Cx43 double-deficient mice. Sodium transients resulted in elevation of intracellular magnesium, indicating a decrease in intracellular ATP. In summary, our results establish that excitatory synaptic activity and stimulation of glutamate uptake in astrocytes trigger transient sodium increases in perivascular endfeet which rapidly spread through gap junctions into neighboring endfeet and cause a reduction of intracellular ATP. The newly discovered endfeet sodium signaling thereby represents a fast, long-lived and inter-cellularly acting indicator of synaptic activity at the blood-brain barrier, which likely constitutes an important component of neuro-metabolic coupling in the brain. GLIA 2017;65:293-308.

Extrusion versus diffusion: mechanisms for recovery from sodium loads in mouse CA1 pyramidal neurons.

KEY POINTS: Neuronal activity causes local or global sodium signalling in neurons, depending on the pattern of synaptic activity. Recovery from global sodium loads critically relies on Na(+) /K(+) -ATPase and an intact energy metabolism in both somata and dendrites. For recovery from local sodium loads in dendrites, Na(+) /K(+) -ATPase activity is not required per se. Instead, recovery is predominately mediated by lateral diffusion, exhibiting rates that are 10-fold higher than for global sodium signals. Recovery from local dendritic sodium increases is still efficient during short periods of energy deprivation, indicating that fast diffusion of sodium to non-stimulated regions strongly reduces local energy requirements. ABSTRACT: Excitatory activity is accompanied by sodium influx into neurones as a result of the opening of voltage- and ligand-activated channels. Recovery from resulting sodium transients has mainly been attributed to Na(+) /K(+) -ATPase (NKA). Because sodium ions are highly mobile, diffusion could provide an additional pathway. We tested this in hippocampal neurones using whole-cell patch-clamp recordings and sodium imaging. Somatic sodium transients induced by local glutamate application recovered at a maximum rate of 8 mm min(-1) (∼0.03 mm min(-1 ) µm(-2) ). Somatic sodium extrusion was accelerated at higher temperature and blocked by ouabain, emphasizing its dependence on NKA. Moreover, it was slowed down during inhibition of glycolysis by sodium fluoride (NaF). Local glutamate application to dendrites revealed a 10-fold higher apparent dendritic sodium extrusion rate compared to somata. Recovery was almost unaltered by increased temperature, ouabain or NaF. We found that sodium diffused along primary dendrites with a diffusion coefficient of ∼330 µm²/s. During global glutamate application, impeding substantial net diffusion, apparent dendritic extrusion rates were reduced to somatic rates and also affected by NaF. Numerical simulations confirmed the essential role of NKA for the recovery of somatic, but not dendritic sodium loads. Our data show that sodium export upon global sodium increases is largely mediated by NKA and depends on an intact energy metabolism. For recovery from local dendritic sodium increases, diffusion dominates over extrusion, operating efficiently even during short periods of energy deprivation. Although sodium will eventually be extruded by the NKA, its diffusion-based fast dissemination to non-stimulated regions might reduce local energy requirements.

Functional anisotropic panglial networks in the lateral superior olive.

Astrocytes form large gap junctional networks that contribute to ion and neurotransmitter homeostasis. Astrocytes concentrate in the lateral superior olive (LSO), a prominent auditory brainstem center. Compared to the LSO, astrocyte density is lower in the region dorsal to the LSO (dLSO) and in the internuclear space between the LSO, the superior paraolivary nucleus (SPN). We questioned whether astrocyte networks exhibit certain properties that reflect the precise neuronal arrangement. Employing whole-cell patch-clamp and concomitant injection of a gap junction-permeable tracer, we analyzed size and orientation of astrocyte networks in LSO, dLSO, and SPN-LSO in acute brainstem slices of mice at postnatal days 10-20. The majority of LSO networks exhibited an oval topography oriented orthogonally to the tonotopic axis, whereas dLSO networks showed no preferred orientation. This correlated with the overall astrocyte morphology in both regions, i.e. LSO astrocyte processes were oriented mainly orthogonally to the tonotopic axis. To assess the spread of small ions within LSO networks, we analyzed the diffusion of Na(+) signals between cells using Na(+) imaging. We found that Na(+) not only diffused between SR101(+) astrocytes, but also from astrocytes into SR101(-) cells. Using PLP-GFP mice for tracing, we could show that LSO networks contained astrocytes and oligodendrocytes. Together, our results demonstrate that LSO astrocytes and LSO oligodendrocytes form functional anisotropic panglial networks that are oriented predominantly orthogonally to the tonotopic axis. Thus, our results point toward an anisotropic ion and metabolite diffusion and a limited glial crosstalk between neighboring isofrequency bands in the LSO. GLIA 2016;64:1892-1911.

Psychological sequelae of surgery in a prospective cohort of patients from three intraoperative awareness prevention trials.

BACKGROUND: Elective surgery can have long-term psychological sequelae, especially for patients who experience intraoperative awareness. However, risk factors, other than awareness, for symptoms of posttraumatic stress disorder (PTSD) after surgery are poorly defined, and practical screening methods have not been applied to a broad population of surgical patients. METHODS: The Psychological Sequelae of Surgery study was a prospective cohort study of patients previously enrolled in the United States and Canada in 3 trials for the prevention of intraoperative awareness. The 68 patients who experienced definite or possible awareness were matched with 418 patients who denied awareness based on age, sex, surgery type, and awareness risk. Participants completed the PTSD Checklist-Specific (PCL-S) and/or a modified Mini-International Neuropsychiatric Interview telephone assessment to identify symptoms of PTSD and symptom complexes consistent with a PTSD diagnosis. We then used structural equation modeling to produce a composite PTSD score and examined potential risk factors. RESULTS: One hundred forty patients were unreachable; of those contacted, 303 (88%) participated a median of 2 years postoperatively. Forty-four of the 219 patients (20.1%) who completed the PCL-S exceeded the civilian screening cutoff score for PTSD symptoms resulting from their surgery (15 of 35 [43%] with awareness and 29 of 184 [16%] without). Nineteen patients (8.7%; 5 of 35 [14%] with awareness and 14 of 184 [7.6%] without) both exceeded the cutoff and endorsed a breadth of symptoms consistent with the Diagnostic and Statistical Manual Fourth Edition diagnosis of PTSD attributable to their surgery. Factors independently associated with PTSD symptoms were poor social support, previous PTSD symptoms, previous mental health treatment, dissociation related to surgery, perceiving that one's life was threatened during surgery, and intraoperative awareness (all P ≤ 0.017). Perioperative dissociation was identified as a potential mediator for perioperative PTSD symptoms. CONCLUSIONS: Events in the perioperative period can precipitate psychological symptoms consistent with subsyndromal and syndromal PTSD. We not only confirmed the high rate of postoperative PTSD in awareness patients but also identified a significant rate in matched nonawareness controls. Screening surgical patients, especially those with potentially mediating risk factors such as intraoperative awareness or perioperative dissociation, for postoperative PTSD symptoms with the PCL-S is practical and could promote early referral, evaluation, and treatment.

Psychometric properties of the gaze anxiety rating scale: convergent, discriminant, and factorial validity.

Fear and avoidance of gaze are two features thought to be associated with problematic social anxiety. Avoidance of eye contact has been linked with such undesirable traits as deceptiveness, insincerity, and lower self-esteem. The Gaze Anxiety Rating Scale (GARS) is a self-report measure designed to assess gaze anxiety and avoidance, but its psychometric properties have only been assessed in one preliminary study. We further investigated psychometric properties of the GARS by assessing convergent and factorial validity. We obtained a two-factor solution: gaze anxiety and avoidance across situations (1) in general (GARS-General) and (2) related to dominance communication (GARS-Dominance). The GARS-General factor related more strongly to social anxiety than the GARS-Dominance, and convergent validity of the factors was supported by expected relationships with personality and social anxiety variables. Our results indicate that the GARS subscales are psychometrically valid measures of gaze aversion, supporting their use in future study of the relationship between social anxiety and eye contact behavior.

Psychosocial competences in the continuing training of French National Education professionals in 2024: A major issue in promoting health in school environment.

OBJECTIVE: Promoting health, and in particular developing psychosocial competences, at school encourages the emancipation of pupils and creates a favourable school environment. Furthermore, by helping to improve academic success, they improve pupils' overall health. However, school professionals need to be trained to develop students' psychosocial competences. The aim of this study was to describe the perceptions of French National Education professionals who have attended in-service training in psychosocial competences. METHOD: This research adopts a mixed methodology. An online questionnaire was administered to 304 professionals in order to measure their levels of satisfaction and professional development following the training. Then, 14 professionals took part in individual semi-structured interviews to discuss their needs and the obstacles and levers they encountered in reinvesting what they had learned into their professional practice. RESULTS: The quantitative data showed that the professionals have an average satisfaction rating ranging from 6.96 to 8.22 out of 10 depending on the variable measured, but that they need to discover more tools and practices to develop psychosocial competences (79.28%). The qualitative data reveal that continuing training enables National Education professionals to exchange ideas with their peers and to review their posture (78.57%). They were able to experiment with psychosocial competences according to their needs and modified their practices as a result of the training (57.14%). CONCLUSION: This study suggests that continuing training in psychosocial competences leads to changes in the attitudes and practices of National Education professionals, despite significant heterogeneity in terms of the length of training. Future research could focus on the actual practices of professionals trained in the development of psychosocial competences in order to assess the difficulties they encounter.

Gap junctions mediate intercellular spread of sodium between hippocampal astrocytes in situ.

Activation of glutamatergic synapses results in long-lasting sodium transients in astrocytes mediated mainly by sodium-dependent glutamate uptake. Sodium elevations activate Na(+) /K(+) -ATPase and glucose uptake by astrocytes, representing key signals for coupling glial metabolism to neuronal activity. Here, we analyzed the spread of sodium signals between astrocytes in hippocampal slice preparations. Stimulation of a single astrocyte resulted in an immediate sodium elevation that spread to neighboring astrocytes within a distance of ∼ 100 µm. Amplitude, slope, and propagation speed of sodium elevations in downstream cells decayed monotonically with increasing distance, indicative of a diffusion process. In contrast to sodium, calcium increases elicited by electrical stimulation were restricted to the stimulated cell and a few neighboring astrocytes. Pharmacological inhibition of mGluR1/5 slightly dampened the spread of sodium, whereas inhibition of glutamate uptake or purinergic receptors had no effect. Spread of sodium to neighboring cells was disturbed on pharmacological inhibition of gap junctions, reduced in animals at P4 and virtually omitted in Cx30/Cx43 double-deficient mice. In contrast to results obtained earlier in cultured astrocytes, our data thus indicate that calcium signaling and metabotropic glutamate receptors are supportive of, but not prerequisites for, the spread of sodium between hippocampal astrocytes in situ, whereas expression of Cx30 and Cx43 is essential. Cx30/Cx43-mediated sodium diffusion between astrocytes could represent a signal indicating increased metabolic needs, independent of concomitant calcium signaling. Spread of sodium might also serve a homeostatic function by supporting the re-establishment of steep sodium gradients and by lowering the metabolic burden imposed on single cells.

The Importance of Awareness, Acceptance, and Alignment With the Self: A Framework for Understanding Self-Connection.

We provide a theoretical framework for what it means to be self-connected and propose that self-connection is an important potential contributor to a person's well-being. We define self-connection as consisting of three components: 1) an awareness of oneself, 2) an acceptance of oneself based on this awareness, and 3) an alignment of one's behavior with this awareness. First, we position the concept within the broader self literature and provide the empirical context for our proposed definition of self-connection. We next compare and contrast self-connection to related constructs, including mindfulness and authenticity. Following, we discuss some of the potential relationships between self-connection and various aspects of mental health and well-being. Finally, we provide initial recommendations for future research, including potential ways to promote self-connection. In all, we present this theory to provide researchers with a framework for understanding self-connection so that they can utilize this concept to better support the efforts of researchers and practitioners alike to increase individuals' well-being in various contexts.

A modular phase transfer and ligand exchange protocol for quantum dots.

In this paper, we describe a quantum dot (qdot) phase transfer protocol using ligand exchange and the amino acid histidine. The phase transfer from nonpolar solvents to aqueous buffers is homogeneous, and no appreciable precipitation occurs. The molecule histidine was chosen in order to first displace the organic encapsulation and second to provide a weakly chemisorbing intermediate at the qdot ionic interface. This allows the histidine to act as an intermediate shell upon which further direct ligand exchange can occur. Since this intermediate encapsulation is easily displaced by an assortment of different molecules while in aqueous buffers, we refer to this approach as modular. Characterization via FTIR and NMR revealed the extent of ligand exchange, and provides insights into the interfacial binding mechanism. The colloidal stability and photostability of the qdots was probed via UV-vis and steady state fluorescence, which revealed promising quantum yield stability of greater than 1 year. The qdots have hydrodynamic diameters of <12 nm and surface charges dependent upon ligand type and coverage. The modularity of this approach is shown by tailoring the qdot surface charge via sequential ligand exchange using mixed monolayers of carboxylic acid and poly(ethylene glycol)-terminated thiols.

Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms.

Inhalation of (nano)particles may lead to pulmonary inflammation. However, the precise mechanisms of particle uptake and generation of inflammatory mediators by alveolar macrophages (AM) are still poorly understood. The aim of this study was to investigate the interactions between particles and AM and their associated pro-inflammatory effects in relation to particle size and physico-chemical properties.NR8383 rat lung AM were treated with ultrafine (uf), fine (f) TiO2 or fine crystalline silica (DQ12 quartz). Physico-chemical particle properties were investigated by transmission electron microscopy, elemental analysis and thermogravimetry. Aggregation and agglomeration tendency of the particles were determined in assay-specific suspensions by means of dynamic light scattering.All three particle types were rapidly taken up by AM. DQ12 and ufTiO2 , but not fTiO2 , caused increased extracellular reactive oxygen species (ROS), heme oxygenase 1 (HO-1) mRNA expression and tumor necrosis factor (TNF)-α release. Inducible nitric oxide synthase (iNOS) mRNA expression was increased most strongly by ufTiO2 , while DQ12 exclusively triggered interleukin (IL) 1ß release. However, oscillations of intracellular calcium concentration and increased intracellular ROS were observed with all three samples. Uptake inhibition experiments with cytochalasin D, chlorpromazine and a Fcγ receptor II (FcγRII) antibody revealed that the endocytosis of fTiO2 by the macrophages involves actin-dependent phagocytosis and macropinocytosis as well as clathrin-coated pit formation, whereas the uptake of ufTiO2 was dominated by FcγIIR. The uptake of DQ12 was found to be significantly reduced by all three inhibitors. Our findings suggest that the contrasting AM responses to fTiO2 , ufTiO2 and DQ12 relate to differences in the involvement of specific uptake mechanisms.

Fostering Stress Resilience Among Business Students: The Role of Stress Mindset and Self-Connection.

Educators are becoming increasingly concerned about the high rates of burnout among their students. Although the solution may appear to be reducing the stress their students experience, simply reducing stress is a temporary solution and does not help students when they enter the workforce and encounter increased stressors. A better option may be to consider the ways in which students can increase stress resilience in ways that will help them long after they leave the classroom. With this idea in mind, we tested for relationships between two individual difference variables, stress mindset and self-connection, and burnout and life satisfaction among business students. The results showed there was a positive relationship between viewing stress as debilitating and prevalence of both personal and school-related burnout. Additionally, self-connection was negatively related to personal burnout and greater life satisfaction. Stress mindset and self-connection also interacted to predict both personal and school burnout. The results suggest that promoting adaptive views of stress and becoming more self-connected may lead to a better student experience.

The Role of Self-Connection in the Relationship between Mindfulness and Meaning: A Longitudinal Examination.

BACKGROUND: Researchers have rarely examined mindfulness and meaning in a way that informs the causality and directionality of this relationship. The current research examines this relationship across time, further validates the Self-Connection Scale (SCS), and examines the role of self-connection in both moderating and mediating this relationship. This allows for researchers and practitioners alike to utilise self-connection to help increase their own and others' well-being. METHODS: One hundred and fifty-four participants completed measures of mindfulness, self-connection, and meaning over 4 weeks. We also included various measures related to well-being to further examine the nomological network of the SCS. RESULTS: Multi-level models examined a total of 432 observations across 108 participants. Mindfulness predicted an increase in the presence of but not search for meaning. Self-connection partially mediated the effect on the presence of meaning and moderated the effect on the search for meaning. Furthermore, the SCS demonstrated good validity and reliability across time. CONCLUSIONS: Self-connection, as measured by the SCS, has an important role in positive psychology, and those with a deficit are likely to benefit the most from increased mindfulness. Together, this provides several implications for using mindfulness and self-connection research in personal and professional practice.

Interpersonal problems in social anxiety disorder across different relational contexts.

People with social anxiety disorder (SAD) frequently report interpersonal problems across various domains; however, it is unclear whether these problems are observable by others or represent negatively biased self-report. We assessed the interpersonal problems of people with and without SAD using self-report, friend, and romantic partner report. We hypothesized that SAD diagnosis would predict self-reported problems across multiple interpersonal domains, but restricted domains of informant report. Additionally, we hypothesized that diagnosis would predict discrepancy between self and informant report either in the form of a bias toward reporting more problems or in the form of lack of concordance between self and informant reporters. Using structural equation and multilevel models, we found evidence for differences between people with and without SAD in terms of domains of impairment observed by self and informants as well as differences in correspondence across relationship types. Results highlight the utility of multi-informant assessment of SAD.

Synaptically induced sodium signals in hippocampal astrocytes in situ.

Astrocytes are in close contact to excitatory synapses and express transporters which mediate the sodium-dependent uptake of glutamate. In cultured astrocytes, selective activation of glutamate transport results in sodium elevations which stimulate Na(+)/K(+)-ATPase and glucose uptake, indicating that synaptic release of glutamate might couple excitatory neuronal activity to glial sodium homeostasis and metabolism. Here, we analysed intracellular sodium transients evoked by synaptic stimulation in acute mouse hippocampal slices using quantitative sodium imaging with the sodium-sensitive fluorescent indicator dye SBFI (sodium-binding benzofuran isophthalate). We found that short bursts of Schaffer collateral stimulation evoke sodium transients in the millimolar range in both CA1 pyramidal neurons and in SR101-positive astrocytes of the stratum radiatum. At low stimulation intensities, glial sodium transients were confined to one to two primary branches and adjacent fine processes and only weakly invaded the soma. Increasing the number of activated afferent fibres by increasing the stimulation intensity elicited global sodium transients detectable in the processes as well as the somata of astrocytes. Pharmacological analysis revealed that neuronal sodium signals were mainly attributable to sodium influx through ionotropic glutamate receptors. Activation of ionotropic receptors also contributed to glial sodium transients, while TBOA-sensitive glutamate transport was the major pathway responsible for sodium influx into astrocytes. Our results thus establish that glutamatergic synaptic transmission in the hippocampus results in sodium transients in astrocytes that are mainly mediated by activation of glutamate transport. They support the proposed link between excitatory synaptic activity, glutamate uptake and sodium signals in astrocytes of the hippocampus.

Far field potentials from brain stem after transcutaneous vagus nerve stimulation: optimization of stimulation and recording parameters.

The method of vagus somatosensory evoked potentials (VSEP) was introduced to easily measure the activity of vagus brain stem nuclei. In Alzheimer's disease, this measure was characterized by longer latencies as compared to controls while amplitudes did not show statistical significant differences at frontal and central recording sites. Therefore, the influence of stimulation and recording parameters on amplitudes of VSEP were systematically examined. In 20 healthy participants, VSEP measurement was done by electrical stimulation of the cutaneous representation of the vagus nerve in the external auditory channel and recording of VSEP over the scalp. The optimum stimulation intensity is 8 mA without perception of pain. There is no effect of stimulation side or gender. Maximum VSEP amplitudes are detected at bipolar recordings comprising the electrode T4 without statistically significant differences of latencies, wave shape and polarity. Thus, recordings of future examinations should be performed at 8 mA including this temporal electrode position. The reason for focussing on brain stem evoked potentials is that recent work has accumulated evidence for this area being involved in early phases of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Improved methodological knowledge may facilitate the assessment of this non-invasive and cost-effective method in the early diagnosis of neurodegenerative disorders.