GABA_{B} Receptors Regulate Chick Retinal Calcium Waves

Correlated spiking activity and associated Ca²⁺ waves in the developing retina are important in determining the connectivity of the visual system. Here, we show that GABA, via GABA_{B} receptors, regulates the temporal characteristics of Ca²⁺ waves occurring before synapse formation in the embryonic chick retina. Blocking ionotropic GABA receptors did no affect these Ca²⁺ transients. However, when these receptors were blocked, GABA abolished the transients, as did the GABA_{B} agonist baclofen. The action of baclofen was prevented by the GABA_{B} antagonistp-3-aminopropyl-p-diethoxymethyl phosphoric acid (CGP35348). CGP35348 alone increased the duration of the transients, showing that GABA_{B} receptors are tonically activated by endogenous GABA. Blocking the GABA transporter GAT-1 with 1-(4,4-diphenyl-3-butenyl)-3-piperidine carboxylic acid (SKF89976A) reduced the frequency of the transients. This reduction was prevented by CGP35348 and thus resulted from activation of GABA_{B} receptors by an increase in external [GABA]. The effect of GABA_{B} receptor activation persisted in the presence of activators and blockers of the cAMP–PKA pathway. Immunocytochemistry showed GABA_{B} receptors and GAT-1 transporters on ganglion and amacrine cells from the earliest times when Ca²⁺ waves occur (embryonic day 8). Patch-clamp recordings showed that K⁺ channels on ganglion cell layer neurons are not modulated by GABA_{B} receptors, whereas Ca²⁺ channels are; however, Ca²⁺ channel blockade with ω-conotoxin-GVIA or nimodipine did not prevent Ca²⁺ waves. Thus, the regulation of Ca²⁺ waves by GABA_{B} receptors occurs independently of N- and L-type Ca²⁺ channels and does not involve K⁺ channels of the ganglion cell layer. GABA_{B} receptors are likely to be of key importance in regulating retinal development

Contextual and endogenous effects on physiology during a haunted house fear induction

Threat exposure elicits physiological and psychological responses, the frequency and intensity of which, and concordance between, has implications for survival. Ethical and practical limitations on human laboratory fear inductions make it essentially impossible to measure response to extreme threat. Furthermore, ecologically valid investigations of group effects on fear are lacking in humans. The current preregistered study measured tonic and phasic electrodermal activity in 156 human participants while they participated in small groups in a 30 minute sequence of threats of varying intensity (a haunted house). Results revealed that (i) friends increased overall arousal, (ii) unexpected attacks elicited greater phasic responses than expected attacks, (iii) subjective fear increased frequency of phasic spikes, and (iv) startle had dissociable effects on frequency and amplitude of phasic reactivity. Findings show that etiology of emotional contagion varies depending on relationship type (increased among friends) and subjective fear is associated with temporal aspects of physiological arousal

Adrenalectomy stimulates hypothalamic proopiomelanocortin expression but does not correct diet-induced obesity

BACKGROUND: Elevated glucocorticoid production and reduced hypothalamic POMC mRNA can cause obese phenotypes. Conversely, adrenalectomy can reverse obese phenotypes caused by the absence of leptin, a model in which glucocorticoid production is elevated. Adrenalectomy also increases hypothalamic POMC mRNA in leptin-deficient mice. However most forms of human obesity do not appear to entail elevated plasma glucocorticoids. It is therefore not clear if reducing glucocorticoid production would be useful to treat these forms of obesity. We hypothesized that adrenalectomy would increase hypothalamic POMC mRNA and reverse obese phenotypes in obesity due to a high-fat diet as it does in obesity due to leptin deficiency. RESULTS: Retired breeder male mice were placed on a high-fat diet or a low-fat diet for two weeks, then adrenalectomized or sham-adrenalectomized. The high-fat diet increased body weight, adiposity, and plasma leptin, led to impaired glucose tolerance, and slightly stimulated hypothalamic proopiomelanocortin (POMC) expression. Adrenalectomy of mice on the high-fat diet significantly reduced plasma corticosterone and strikingly increased both pituitary and hypothalamic POMC mRNA, but failed to reduce body weight, adiposity or leptin, although slight improvements in glucose tolerance and metabolic rate were observed. CONCLUSION: These data suggest that neither reduction of plasma glucocorticoid levels nor elevation of hypothalamic POMC expression is effective to significantly reverse diet-induced obesity

Reducing hypothalamic AGRP by RNA interference increases metabolic rate and decreases body weight without influencing food intake

BACKGROUND: Several lines of evidence strongly suggest that agouti-related peptide (AGRP) plays a key role in the regulation of metabolic function but ablation of the AGRP gene has no apparent effect on metabolic function. Since specific pharmacological antagonists of AGRP do not presently exist, we assessed if reduction of hypothalamic AGRP mRNA by RNA interference (RNAI) would influence metabolic function, an outcome suggesting that pharmacological antagonists might constitute useful reagents to treat obesity. RESULTS: The RNAI protocol specifically reduced hypothalamic expression of AGRP mRNA by 50% and resulted in reduction of AGRP peptide immunoreactivity. Physiologically, the reduction in AGRP levels was associated with increased metabolic rate and reduced body weight without changes in food intake. CONCLUSION: AGRP can function to increase body weight and reduce metabolic rate without influencing food intake. The present study demonstrates that RNAI protocols can be used to assess physiological function of neuronal genes in vivo

Mental health and unemployment: A systematic review and meta-analysis of interventions to improve depression and anxiety outcomes

Background: Unemployment is associated with substantially greater depression and anxiety, constituting a considerable public health concern. The current review provides the most comprehensive synthesis to date, and first meta-analysis, of controlled intervention trials aimed at improving depression and anxiety outcomes during unemployment. Methods: Searches were conducted within PsycInfo, Cochrane Central, PubMed and Embase from their inception to September 2022. Included studies conducted controlled trials of interventions focused on improving mental health within unemployed samples, and reported on validated measures of depression, anxiety, or distress (mixed depression and anxiety). Narrative syntheses and random effects meta-analyses were conducted among prevention- and treatment-level interventions for each outcome. Results: A total of 39 articles reporting on 33 studies were included for review (sample sizes ranging from 21 to 1801). Both prevention and treatment interventions tended to be effective overall, with treatment interventions producing larger effect sizes than prevention interventions. The clearest evidence for particular intervention approaches emerged for prevention-level Cognitive Therapy/CBT, followed by prevention-level work-related interventions, although neither produced entirely consistent effects. Limitations: Risk of bias was generally high across studies. Low numbers of studies within subgroups precluded any comparisons between long-term and short-term unemployment, limited comparisons among treatment studies, and reduced the power of meta-analyses. Conclusions: Both prevention- and treatment-level mental health-focused interventions have merit for reducing symptoms of anxiety and depression among those experiencing unemployment. Cognitive Therapy/CBT and work-related interventions hold the most robust evidence base, which can inform both prevention and treatment strategies implemented by clinicians, employment services providers, and governments

Low-Froude-number stable flows past mountains

A new approximate analysis is presented for stably stratified flows at low Froude number F past mountains of heightH. In the “top” layer where the streamlines pass above the surface of themountain, there is a perturbation flow. This approximately matches the lower flow in the “middle” ‘horizontal’ layer [M] in which the streamlines pass round the mountain in nearly horizontal planes, as in Drazin’s (DRAZIN P. G., On the steady flow of a fluid of variable density past an obstacle, Tellus, 13 (1961) 239-251) model. The pressure associated with the diverging streamlines on the lee side of the summit layer flow drives the separated flow in the horizontal layer (which is not included in Drazin’s model). This explains the vortical wake flow in experiments and in the “inviscid” computations of Smolarkiewicz and Rotunno (SMOLARKIEWICZ P. K. and ROTUNNO R., Low Froude number flow past three-dimensional obstacles. Part I: Baroclinically generated lee vortices, J. Atmos. Sci., 46 (1989) 1154-1164). A method for estimating the height HT FH of the cut-off mountain is derived, as a function of upstream shear, mountain shape and other parameters. Recent laboratory experiments have confirmed how the curvature of the oncoming shear flow profile

Role of glucocorticoids in mediating effects of fasting and diabetes on hypothalamic gene expression

BACKGROUND: Fasting and diabetes are characterized by elevated glucocorticoids and reduced insulin, leptin, elevated hypothalamic AGRP and NPY mRNA, and reduced hypothalamic POMC mRNA. Although leptin replacement can reverse changes in hypothalamic gene expression associated with fasting and diabetes, leptin also normalizes corticosterone; therefore the extent to which the elevated corticosterone contributes to the regulation of hypothalamic gene expression in fasting and diabetes remains unclear. To address if elevated corticosterone is necessary for hypothalamic responses to fasting and diabetes, we assessed the effects of adrenalectomy on hypothalamic gene expression in 48-hour-fasted or diabetic mice. To assess if elevated corticosterone is sufficient for the hypothalamic responses to fasting and diabetes, we assessed the effect of corticosterone pellets implanted for 48 hours on hypothalamic gene expression. RESULTS: Fasting and streptozotocin-induced diabetes elevated plasma glucocorticoid levels and reduced serum insulin and leptin levels. Adrenalectomy prevented the rise in plasma glucocorticoids associated with fasting and diabetes, but not the associated reductions in insulin or leptin. Adrenalectomy blocked the effects of fasting and diabetes on hypothalamic AGRP, NPY, and POMC expression. Conversely, corticosterone implants induced both AGRP and POMC mRNA (with a non-significant trend toward induction of NPY mRNA), accompanied by elevated insulin and leptin (with no change in food intake or body weight). CONCLUSION: These data suggest that elevated plasma corticosterone mediate some effects of fasting and diabetes on hypothalamic gene expression. Specifically, elevated plasma corticosterone is necessary for the induction of NPY mRNA with fasting and diabetes; since corticosterone implants only produced a non-significant trend in NPY mRNA, it remains uncertain if a rise in corticosterone may be sufficient to induce NPY mRNA. A rise in corticosterone is necessary to reduce hypothalamic POMC mRNA with fasting and diabetes, but not sufficient for the reduction of hypothalamic POMC mRNA. Finally, elevated plasma corticosterone is both necessary and sufficient for the induction of hypothalamic AGRP mRNA with fasting and diabetes

The role of wearable devices and objective gait analysis for the assessment and monitoring of patients with lumbar spinal stenosis: Systematic review

© 2019 The Author(s). Background: The purpose of this systematic review was to evaluate the accuracy and reliability of wearable devices for objective gait measurement of Lumbar Spinal Stenosis (LSS) patients, with a focus on relevant gait metrics. Methods: Systematic searches were conducted of five electronic databases to identify studies that assessed gait metrics by wearable or portable technology. Data was collected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. Results: Four articles were identified for inclusion in this review. The objectives, methodology and quality of the studies varied. No single gait metric was investigated in all four studies, making comparison difficult. The most relevant metrics reported included gait cycle, gait velocity, step length and cadence, which were reported in two studies. Two studies explored gait symmetry. Differences between LSS patients and normal healthy subjects are demonstrable using wearable technology. Conclusions: The measurements of gait cycle, cadence, step length, gait velocity, and number of steps with wearable devices can be used in the gait measurement of LSS patients for initial assessment, and objective outcomes following interventions. However, data and analysis are limited, and further studies are necessary to comment on reliability