High fat diet-induced obesity causes a reduction in brain tyrosine hydroxylase levels and non-motor features in rats through metabolic dysfunction, neuroinflammation and oxidative stress.

Obesity is a health problem that has been associated with neuroinflammation, decreased cognitive functions and development of neurodegenerative diseases. Parkinson's disease (PD) is a chronic neurodegenerative condition characterized by motor and non-motor abnormalities, increased brain inflammation, α-synuclein protein aggregation and dopaminergic neuron loss that is associated with decreased levels of tyrosine hydroxylase (TH) in the brain. Diet-induced obesity is a global epidemic and its role as a risk factor for PD is not clear. Herein, we showed that 25 weeks on a high-fat diet (HFD) promotes significant alterations in the nigrostriatal axis of Wistar rats. Obesity induced by HFD exposure caused a reduction in TH levels and increased TH phosphorylation at serine 40 in the ventral tegmental area. These effects were associated with insulin resistance, increased tumor necrosis factor-α levels, oxidative stress, astrogliosis and microglia activation. No difference was detected in the levels of α-synuclein. Obesity also induced impairment of locomotor activity, total mobility and anxiety-related behaviors that were identified in the open-field and light/dark tasks. There were no changes in motor coordination or memory. Together, these data suggest that the reduction of TH levels in the nigrostriatal axis occurs through an α-synuclein-independent pathway and can be attributed to brain inflammation, oxidative/nitrosative stress and metabolic disorders induced by obesity.

The astrocyte biochemistry.

Astrocytes are a unique and dynamic subtype of glial cells in the central nervous system (CNS). Understanding their biochemical reactions and their influence in the surrounding cells is extremely important in the neuroscience field. They exert important influence in the neurotransmission, ionic homeostasis and also release neuroactive molecules termed gliotransmitters. Additionally, they metabolize, store and release metabolic substrates to meet high brain energy requirements. In this review, we highlight the main biochemical reactions regarding energy metabolism that take place in astrocytes. Special attention is given to synthesis, storage and catabolism of glucose, release of lactate, oxidation of fatty acids, production of ketone bodies, and metabolism of the main neurotransmitters, glutamate and GABA. The recent findings allow proposing these cells as key players controlling the energetic homeostasis in the CNS.

Category-specific verb-semantic deficits in Alzheimer's disease: Evidence from static and dynamic action naming.

We investigated the representation and breakdown of verb knowledge employing different syntactic and semantic classes of verbs in a group of individuals with probable Alzheimer's Disease (pAD). In an action naming task with coloured photographs (Fiez & Tranel, 1997. Standardized stimuli and procedures for investigating the retrieval of lexical and conceptual knowledge for action. Memory and Cognition, 25(4), 543-569. https://doi.org/10.3758/BF03201129), pAD individuals were impaired for naming actions compared to objects. Verb tense was also affected, with simple-past (e.g., chopped) being more difficult to name than the gerundial form (e.g., chopping). Employing action-naming with short movies depicting events and states, we contrasted three verb classes based on their hypothetical structural and semantic/conceptual properties: argument structure, thematic structure, and conceptual templates. The three classes were: causatives (peel), verbs of perception (hear), and verbs of motion (run) Overall, results suggest that individuals with pAD are selectively impaired for verb tense and thematic assignment, but not conceptual-template complexity. Methodologically, we also show that dynamic scenes are more ecologically valid than static scenes to probe verb knowledge in AD.

Effects of intranasal guanosine administration on brain function in a rat model of ischemic stroke.

Ischemic stroke is a major cause of morbidity and mortality worldwide and only few affected patients are able to receive treatment, especially in developing countries. Detailed pathophysiology of brain ischemia has been extensively studied in order to discover new treatments with a broad therapeutic window and that are accessible to patients worldwide. The nucleoside guanosine (Guo) has been shown to have neuroprotective effects in animal models of brain diseases, including ischemic stroke. In a rat model of focal permanent ischemia, systemic administration of Guo was effective only when administered immediately after stroke induction. In contrast, intranasal administration of Guo (In-Guo) was effective even when the first administration was 3 h after stroke induction. In order to validate the neuroprotective effect in this larger time window and to investigate In-Guo neuroprotection under global brain dysfunction induced by ischemia, we used the model of thermocoagulation of pial vessels in Wistar rats. In our study, we have found that In-Guo administered 3 h after stroke was capable of preventing ischemia-induced dysfunction, such as bilateral suppression and synchronicity of brain oscillations and ipsilateral cell death signaling, and increased permeability of the blood-brain barrier. In addition, In-Guo had a long-lasting effect on preventing ischemia-induced motor impairment. Our data reinforce In-Guo administration as a potential new treatment for brain ischemia with a more suitable therapeutic window.

Neuroprotective Effects of Guanosine Administration on In Vivo Cortical Focal Ischemia in Female and Male Wistar Rats.

Guanosine (GUO) has neuroprotective effects in experimental models of brain diseases involving glutamatergic excitotoxicity in male animals; however, its effects in female animals are poorly understood. Thus, we investigated the influence of gender and GUO treatment in adult male and female Wistar rats submitted to focal permanent cerebral ischemia in the motor cortex brain. Female rats were subdivided into non-estrogenic and estrogenic phase groups by estrous cycle verification. Immediately after surgeries, the ischemic animals were treated with GUO or a saline solution. Open field and elevated plus maze tasks were conducted with ischemic and naïve animals. Cylinder task, immunohistochemistry and infarct volume analyses were conducted only with ischemic animals. Female GUO groups achieved a full recovery of the forelimb symmetry at 28-35 days after the insult, while male GUO groups only partially recovered at 42 days, in the final evaluation. The ischemic insult affected long-term memory habituation to novelty only in female groups. Anxiety-like behavior, astrocyte morphology and infarct volume were not affected. Regardless the estrous cycle, the ischemic injury affected differently female and male animals. Thus, this study points that GUO is a potential neuroprotective compound in experimental stroke and that more studies, considering the estrous cycle, with both genders are recommended in future investigation concerning brain diseases.

Effect of a trans fatty acid-enriched diet on mitochondrial, inflammatory, and oxidative stress parameters in the cortex and hippocampus of Wistar rats.

PURPOSE: Previously showed that dietary trans fatty acids (TFAs) may cause systemic inflammation and affect the central nervous system (CNS) in Wistar rats by increased levels of cytokines in the cerebrospinal fluid (CSF) and serum (Longhi et al. Eur J Nutr 56(3):1003-1016, 1). Here, we aimed to clarifying the impact of diets with different TFA concentrations on cerebral tissue, focusing on hippocampus and cortex and behavioral performance. METHODS: Wistar rats were fed either a normolipidic or a hyperlipidic diet for 90 days; diets had the same ingredients except for fat compositions, concentrations, and calories. We used lard in the cis fatty acid (CFA) group and PHSO in the TFA group. The intervention groups were as follows: (1) low lard (LL), (2) high lard (HL), (3) low partially hydrogenated soybean oil (LPHSO), and (4) high partially hydrogenated soybean oil (HPHSO). Mitochondrial parameters, tumor necrosis factor alpha (TNF-α), 2'7'-dichlorofluorescein (DCFH) levels in brain tissue, and open field task were analyzed. RESULTS: A worse brain tissue response was associated with oxidative stress in cortex and hippocampus as well as impaired inflammatory and mitochondrial parameters at both PHSO concentrations and there were alterations in the behavioral performance. In many analyses, there were no significant differences between the LPHSO and HPHSO diets. CONCLUSIONS: Partially hydrogenated soybean oil impaired cortical mitochondrial parameters and altered inflammatory and oxidative stress responses, and the hyperlipidic treatment caused locomotor and exploratory effects, but no differences on weight gain in all treatments. These findings suggest that quality is more important than the quantity of fat consumed in terms of CFA and TFA diets.

Chronic Stress Causes Sex-Specific and Structure-Specific Alterations in Mitochondrial Respiratory Chain Activity in Rat Brain.

Chronic restraint stress (CRS) induces a variety of changes in brain function, some of which are mediated by glucocorticoids. The response to stress occurs in a sex-specific way, and may include mitochondrial and synaptic alterations. The synapse is highly dependent on mitochondrial energy supply, and when mitochondria become dysfunctional, they orchestrate cell death. This study aimed to investigate the CRS effects on mitochondrial respiratory chain activity, as well as mitochondrial potential and mass in cell body and synapses using hippocampus, cortex and striatum of male and female rats. Rats were divided into non-stressed (control) and stressed group (CRS during 40 days). Results showed that CRS increased complex I-III activity in hippocampus. We also observed an interaction between CRS and sex in the striatal complex II activity, since CRS induced a reduction in complex II activity in males, while in females this activity was increased. Also an interaction was observed between stress and sex in cortical complex IV activity, since CRS induced increased activity in females, while it was reduced in males. Glucocorticoid receptor (GR) content in cortex and hippocampus was sexually dimorphic, with female rats presenting higher levels compared to males. No changes were observed in GR content, mitochondrial potential or mass of animals submitted to CRS. It was concluded that CRS induced changes in respiratory chain complex activities, and some of these changes are sex-dependent: these activities are increased in the striatal mitochondria by CRS protocol mainly in females, while in males it is decreased.

Effect of a trans fatty acid-enriched diet on biochemical and inflammatory parameters in Wistar rats.

PURPOSE: Recent data regarding trans fatty acids (TFAs) have implicated these lipids as particularly deleterious to human health, causing systemic inflammation, endothelial dysfunction and possibly inflammation in the central nervous system (CNS). We aimed to clarify the impact of partially hydrogenated soybean oil (PHSO) with different TFA concentrations on cerebrospinal fluid (CSF), serum and hepatic parameters in adult Wistar rats. METHODS: Wistar rats (n = 15/group) were fed either a normolipidic diet or a hyperlipidic diet for 90 days. The normolipidic and hyperlipidic diets had the same ingredients except for fat compositions, concentrations and calories. We used lard in the cis fatty acid group and PHSO in the trans fatty acid group. The intervention groups were as follows: (1) low lard (LL), (2) high lard (HL), (3) low partially hydrogenated soybean oil (LPHSO) and (4) high partially hydrogenated soybean oil (HPHSO). Body weight, lipid profiles and the inflammatory responses in the CSF, serum and liver tissue were analyzed. RESULTS: Surprisingly, with the PHSO diet we observed a worse metabolic response that was associated with oxidative stress in hepatic tissue as well as impaired serum and CSF fluid parameters at both PHSO concentrations. In many analyses, there were no significant differences between the LPHSO and HPHSO diets. CONCLUSIONS: Dietary supplementation with PHSO impaired inflammatory parameters in CSF and blood, induced insulin resistance, altered lipid profiles and caused hepatic damage. Overall, these findings suggest that fat composition is more important than the quantity of fat consumed in terms of cis and trans fatty acid diets.

Participation of α2 -adrenoceptors in sodium appetite inhibition during sickness behaviour following administration of lipopolysaccharide.

Sickness behaviour, a syndrome characterized by a general reduction in animal activity, is part of the active-phase response to fight infection. Lipopolysaccharide (LPS), an effective endotoxin to model sickness behaviour, reduces thirst and sodium excretion, and increases neurohypophysial secretion. Here we review the effects of LPS on thirst and sodium appetite. Altered renal function and hydromineral fluid intake in response to LPS occur in the context of behavioural reorganization, which manifests itself as part of the syndrome. Recent data show that, in addition to its classical effect on thirst, non-septic doses of LPS injected intraperitoneally produce a preferential inhibition of intracellular thirst versus extracellular thirst. Moreover, LPS also reduced hypertonic NaCl intake in sodium-depleted rats that entered a sodium appetite test. Antagonism of α2 -adrenoceptors abolished the effect of LPS on sodium appetite. LPS and cytokine transduction potentially recruit brain noradrenaline and α2 -adrenoceptors to control sodium appetite and sickness behaviour.

Intranasal guanosine administration presents a wide therapeutic time window to reduce brain damage induced by permanent ischemia in rats.

In addition to its intracellular roles, the nucleoside guanosine (GUO) also has extracellular effects that identify it as a putative neuromodulator signaling molecule in the central nervous system. Indeed, GUO can modulate glutamatergic neurotransmission, and it can promote neuroprotective effects in animal models involving glutamate neurotoxicity, which is the case in brain ischemia. In the present study, we aimed to investigate a new in vivo GUO administration route (intranasal, IN) to determine putative improvement of GUO neuroprotective effects against an experimental model of permanent focal cerebral ischemia. Initially, we demonstrated that IN [(3)H] GUO administration reached the brain in a dose-dependent and saturable pattern in as few as 5 min, presenting a higher cerebrospinal GUO level compared with systemic administration. IN GUO treatment started immediately or even 3 h after ischemia onset prevented behavior impairment. The behavior recovery was not correlated to decreased brain infarct volume, but it was correlated to reduced mitochondrial dysfunction in the penumbra area. Therefore, we showed that the IN route is an efficient way to promptly deliver GUO to the CNS and that IN GUO treatment prevented behavioral and brain impairment caused by ischemia in a therapeutically wide time window.

Shading effect on microclimate and thermal comfort indexes in integrated crop-livestock-forest systems in the Brazilian Midwest.

The objective of this paper was to perform a microclimate evaluation and determine the indexes of thermal comfort indexes, in sun and shade, in integrated crop-livestock-forest systems with different arrangements of eucalyptus and native trees, in the Brazilian Midwest. The experiment was conducted at Embrapa Beef Cattle in Campo Grande, state of Mato Grosso do Sul, Brazil, from July to September 2013. The evaluations were conducted on four consecutive days, from 8:00 a.m. to 5:00 p.m., local time (GMT -4:00), with 1 hour intervals, recording the microclimate parameters: air temperature (°C), black globe temperature (°C), wet bulb temperature (°C), relative humidity (%), and wind speed (m.s-1), for the subsequent calculation of the Temperature and Humidity Index, the Black Globe Temperature and Humidity Index, and the Radiant Thermal Load. The largest changes in microclimate parameters were found in the full sun, between 12:00 p.m. and 1:00 p.m., in less dense eucalyptus system, followed by the scattered native trees system, resulting in a maximum Temperature and Humidity Index of 81, Black Globe Temperature and Humidity Index of 88 and Radiant Thermal Load of 794 W m-2. Therefore, it is observed that with the presence of trees in pastures were possible reductions of up to 3.7 % in Temperature and Humidity Index, 10.2 % in the Black Globe Temperature and Humidity Index, and 28.3 % of the Radiant Thermal Load in the shade. Thus, one can conclude that the presence of trees and their arrangement in the systems provide better microclimate conditions and animal thermal comfort in pastures.

Retzus-sparing robotic-assisted laparoscopic radical prostatectomy: a step-by-step technique description of this first brazilian experience.

INTRODUCTION: Retzus-sparing robotic-assisted radical prostatectomy(RARP) is a newly approach that preserve the Retzus structures and provide better recovery of continence and erectile function. In Brazil, this approach has not yet been pre¬viously reported. OBJECTIVE: Our goal is to describe Step-by-Step the Retzus-sparing RARP surgical technique and report our first Brazilian experience. METHODS: We present a case of a 60-year-old white man with low risk prostate cancer. Surgical materials were four arms Da Vinci robotic platform system, six transperitoneal portals, two prolene wires and Polymer Clips. This surgical tech¬nique was step-by-step described according to Galfano et al. One additional step was added as a modification of Galfano et al. Primary technique description: The closure of the Denovellier fascia. RESULTS: We have operated one patient with this technique. The operative time was 180minutes, console time was135 min, the blood loss was 150ml, none perioperative or postoperative complications was found, hospital stay of 01 day. The anatomopathological classification revealed a pT2aN0M0 specimen with free surgical margins. The patient achieved continence immediately after bladder stent retrieval. Full erection reported after 30 days of surgery. CONCLUSION: Retzus-sparing RARP approach is feasible and reproducible. However, further comparative studies are neces¬sary to demonstrate potential benefits in continence and sexual outcomes over the standard approaches.

Semantic properties, aptness, familiarity, conventionality, and interpretive diversity scores for 84 metaphors and similes.

For 84 unique topic-vehicle pairs (e.g., knowledge-power), participants produced associated properties for the topics (e.g., knowledge), vehicles (e.g., power), metaphors (knowledge is power), and similes (knowledge is like power). For these properties, we also obtained frequency, saliency, and connotativeness scores (i.e., how much the properties deviated from the denotative or literal meaning). In addition, we examined whether expression type (metaphor vs. simile) impacted the interpretations produced. We found that metaphors activated more salient properties than did similes, but the connotativeness levels for metaphor and simile salient properties were similar. Also, the two types of expressions did not differ across a wide range of measures collected: aptness, conventionality, familiarity, and interpretive diversity scores. Combined with the property lists, these interpretation norms constitute a thorough collection of data about metaphors and similes, employing the same topic-vehicle words, which can be used in psycholinguistic and cognitive neuroscience studies to investigate how the two types of expressions are represented and processed. These norms should be especially useful for studies that examine the online processing and interpretation of metaphors and similes, as well as for studies examining how properties related to metaphors and similes affect the interpretations produced.

Performance of Nellore heifers, forage mass, and structural and nutritional characteristics of Brachiaria brizantha grass in integrated production systems.

Our objective was to evaluate production, nutritive value and carrying capacity of piatã grass (Brachiaria brizantha cv. BRS Piatã), and performance of Nellore heifers in agrosilvopastoral systems (ASPS) with three eucalyptus (Eucalyptus urograndis) tree densities, during winter, spring, summer, and fall. Three integrated systems were evaluated: ASPS-1 (357 trees ha(-1)), ASPS-2 (227 trees ha(-1)), and CON (5 trees ha(-1)). In each system, two sward heights were evaluated: short and tall. A total of 80 11-month-old Nellore heifers were randomly allocated in a randomized split-plot block, 3 × 2 factorial. Greater dry matter availability was observed on CON pastures during the fall season. Greater percentage of leaf lamina was detected on ASPS-1 with short sward height and greater during summer, compared with other seasons. A greater forage production was observed between tree rows and for tall sward height. Spring was the season with less forage nutritive value. Average daily gain was greater during summer and fall. Gain per hectare and stocking rate were greater on CON system and on ASPS-2. Pastures with short sward height had greater gain per hectare and stocking rate. Agrosilvopastoral systems with intermediate tree density seem to be a good choice for producers willing to diversify their revenue sources without decreasing animal production.

Histone 3 Trimethylation Patterns are Associated with Resilience or Stress Susceptibility in a Rat Model of Major Depression Disorder.

Major Depressive Disorder (MDD) is a severe and multifactorial psychiatric condition. Evidence has shown that environmental factors, such as stress, significantly explain MDD pathophysiology. Studies have hypothesized that changes in histone methylation patterns are involved in impaired glutamatergic signaling. Based on this scenario, this study aims to investigate histone 3 involvement in depression susceptibility or resilience in MDD pathophysiology by investigating cellular and molecular parameters related to i) glutamatergic neurotransmission, ii) astrocytic functioning, and iii) neurogenesis. For this, we subjected male Wistar rats to the Chronic Unpredictable Mild Stress (CUMS) model of depression. We propose that by evaluating the sucrose consumption, open field, and object recognition test performance from animals submitted to CUMS, it is possible to predict with high specificity rats with susceptibility to depressive-like phenotype and resilient to the depressive-like phenotype. We also demonstrated, for the first time, that patterns of H3K4me3, H3K9me3, H3K27me3, and H3K36me3 trimethylation are strictly associated with the resilient or susceptible to depressive-like phenotype in a brain-region-specific manner. Additionally, susceptible animals have reduced DCx and GFAP and resilient animals present increase of AQP-4 immunoreactivity. Together, these results provide evidence that H3 trimethylations are related to the development of the resilient or susceptible to depressive-like phenotype, contributing to further advances in the pathophysiology of MDD and the discovery of mechanisms behind resilience.

Early-life trauma, impulsivity and suicide attempt: a systematic review and meta-analysis.

INTRODUCTION: Suicide is a worldwide health concern and up to date there is no good predictor of it except a previous suicide attempt. Therefore, there are increasing efforts in the understanding of which factors, genetic or environmental, are associated with suicide behaviour. OBJECTIVE: To review evidence of the effect of childhood trauma and impulsivity on suicidal behavior through a systematic review and meta-analysis. METHODS: Searches were conducted on the 12th of June 2021 in the PubMed, Scopus, and Web of Science databases. Two reviewers evaluated each record for eligibility and discussed upon disagreement, when no consensus was reached, a third reviewer was involved to make a decision. RESULTS: A total of 11,530 records were identified through the searches. After duplicates were removed, 6,595 records remained to be screened. The full text was sought for 1,561 records. Our qualitative synthesis included 22 studies, from which 9 were included in the meta-analyses. We found a significant effect of sexual abuse, physical abuse, emotional abuse and physical neglect on suicide attempts in the prisoners, and Substance Use Diorder (SUD) subgroups. Moreover, there was a significant effect of Childhood Trauma Questionnaire (CTQ) total score and emotional neglect dimension for all the subgroups. CONCLUSION: The present study has provided an overview of the state-of-the-art research on childhood trauma and impulsivity and their association with suicidal behavior and quantified their effects on suicide attempts. Hopefully this evidence will be considered in future research and harnessed for clinical gain in detection and treatment of suicide behaviour.

Lifestyle and Sense of Coherence: A comparative analysis among university students in different areas of knowledge.

BACKGROUND: The concept of health has undergone profound changes. Lifestyle Medicine consists of therapeutic approaches that focus on the prevention and treatment of diseases. It follows that the quality of life of university students directly affects their health and educational progress. EXPERIMENTAL METHODOLOGY: Socioeconomic, lifestyle (LS), and Salutogenesis Theory/sense of coherence (SOC) questionnaires were administered to college students from three different areas. The results were analyzed for normality and homogeneity, followed by ANOVA variance analysis and Dunn and Tukey post hoc test for multiple comparisons. Spearman's correlation coefficient evaluated the correlation between lifestyle and sense of coherence; p values < 0.05 were considered statistically significant. RESULTS: The correlation between LS and SOC was higher among males and higher among Medical and Human sciences students compared to Exact sciences. Medical students' scores were higher than Applied sciences and Human sciences students on the LS questionnaire. Exact science students' scores on the SOC questionnaire were higher than Human sciences students. In the LS areas related to alcohol intake, sleeping quality, and behavior, there were no differences between the areas. However, women scored better in the nutrition domain and alcohol intake. The SOC was also higher in men compared to women. CONCLUSION: The results obtained demonstrate in an unprecedented way in the literature that the correlation between the LS and SOC of college students varies according to gender and areas of knowledge, reflecting the importance of actions on improving students' quality of life and enabling better academic performance.

Evaluating the Antischistosomal Activity of Dehydrodieugenol B and Its Methyl Ether Isolated from Nectandra leucantha-A Preclinical Study against Schistosoma mansoni Infection.

Schistosomiasis, a parasitic disease affecting nearly 250 million individuals globally, poses a significant health challenge. With praziquantel being the sole available treatment and its limited efficacy in early stage infections, the identification of novel bioactive compounds becomes imperative. This study examines the potential of dehydrodieugenol B (1) and its methyl ether (2), derived from the leaves of the Brazilian Nectandra leucantha plant (Lauraceae), in combatting Schistosoma mansoni infections through a preclinical approach. Initially, compound 1 displayed noteworthy in vitro antiparasitic activity with an EC50 of 31.9 µM, showcasing low toxicity in mammalian cells and an in vivo animal model (Caenorhabditis elegans). Conversely, compound 2 exhibited no activity. In silico predictions pointed to favorable oral bioavailability and the absence of PAINS similarities. Subsequently, a single oral dose of 400 mg/kg of compound 1 or praziquantel was administered to mice infected with adult (patent infection) or immature parasites (prepatent infection). Remarkably, in prepatent infections, 1 resulted in a significant reduction (approximately 50%) in both worm and egg burden, while praziquantel reduced worm and egg numbers by 30%. The superior efficacy of dehydrodieugenol B (1) compared to praziquantel in premature infections holds the potential to advance the development of new molecular prototypes for schistosomiasis treatment.

Binge-like ethanol exposure during the brain growth spurt disrupts the function of retrosplenial cortex-projecting anterior thalamic neurons in adolescent mice.

Ethanol (EtOH) exposure during late pregnancy leads to enduring impairments in learning and memory that may stem from damage to components of the posterior limbic memory system, including the retrosplenial cortex (RSC) and anterior thalamic nuclei (ATN). In rodents, binge-like EtOH exposure during the first week of life (equivalent to the third trimester of human pregnancy) triggers apoptosis in these brain regions. We hypothesized that this effect induces long-lasting alterations in the function of RSC-projecting ATN neurons. To test this hypothesis, vesicular GABA transporter-Venus mice (expressing fluorescently tagged GABAergic interneurons) were subjected to binge-like EtOH vapor exposure on postnatal day (P) 7. This paradigm activated caspase 3 in the anterodorsal (AD), anteroventral (AV), and reticular thalamic nuclei at P7 but did not reduce neuronal density in these areas at P60-70. At P40-60, we injected red retrobeads into the RSC and performed patch-clamp slice electrophysiological recordings from retrogradely labeled neurons in the AD and AV nuclei 3-4 days later. We found significant effects of treatment on instantaneous action potential (AP) frequency and AP overshoot, as well as sex × treatment interactions for AP threshold and overshoot in AD neurons. A sex × treatment interaction was detected for AP number in AV neurons. EtOH exposure also reduced the frequency and amplitude of spontaneous excitatory postsynaptic currents and increased the charge transfer of spontaneous inhibitory postsynaptic currents. These results highlight a novel cellular mechanism that could contribute to the lasting learning and memory deficits associated with developmental EtOH exposure.

Learning to treat the climate emergency together: social tipping interventions by the health community.

Accelerating the decarbonisation of local and national economies is a profound public health imperative. As trusted voices within communities around the world, health professionals and health organisations have enormous potential to influence the social and policy landscape in support of decarbonisation. We assembled a multidisciplinary, gender-balanced group of experts from six continents to develop a framework for maximising the social and policy influence of the health community on decarbonisation at the micro levels, meso levels, and macro levels of society. We identify practical, learning-by-doing approaches and networks to implement this strategic framework. Collectively, the actions of health-care workers can shift practice, finance, and power in ways that can transform the public narrative and influence investment, activate socioeconomic tipping points, and catalyse the rapid decarbonisation needed to protect health and health systems.