In vivo stimulation of locus coeruleus: effects on amygdala subnuclei

The locus coeruleus (LC) is the major noradrenergic nucleus and sends projections to almost all brain areas. A marked increase in norepinephrine release has been demonstrated in several brain areas in response to exposure to acute stressful stimuli, especially those innervated by LC projections. One of the brain areas innervated by LC neurons is the amygdala, a structure highly involved in emotional processes and memory formation. The aim of this study was to increase knowledge of the functional connectivity between the LC and the amygdala subnuclei. To reach this objective, we evaluated c‑fos immunoreactive cells in amygdala nuclei following direct electrical stimulation of the LC in conscious animals. This analysis of c‑fos immunoreactivity could inform whether there are differences in activity of the amygdala subnuclei related to LC electrical stimulation in conscious animals. Our results showed a marked increase in c‑fos activity in these amygdala subnuclei both ipsilateral and contralateral to LC electrical stimulation in vivo. Therefore, our study provides evidence that in vivo electrical stimulation of LC is able to activate the amygdala subnuclei as measured by c‑fos expression

Environmental Enrichment Modulates Drug Addiction and Binge-Like Consumption of Highly Rewarding Substances: A Role for Anxiety and Compulsivity Brain Systems?

Drug addiction is a chronic disorder comprising components of both impulsivity and compulsivity in the so called “addiction cycle” which develops over time from early non-dependent, repetitive, binge-consumption to later post-dependent compulsive consumption. Thus, frequent binge-like intake is a typical pattern of excessive drug intake characteristic of the pre-dependent phase of the addiction cycle, which represent an important risk factor to develop addiction in vulnerable individuals. In this framework, it is of paramount interest to further understand the earliest stage of the addiction cycle so novel approaches would emerge aimed to control repetitive episodes of binge-consumption in non-dependent subjects, protecting vulnerable individuals from transition to dependence. Environmental enrichment (EE) is a preclinical animal model in which animals are housed under novel, social enriched conditions, which allows exercising and provides sensory and cognitive stimulation. EE promotes important improvements for a variety of cognitive processes and clear therapeutic and protective effects preventing ethanol (EtOH) and drug addiction as well. Interestingly, recent observations suggest that EE might additionally modulate binge-like intake of highly palatable caloric substances, including EtOH, which suggests the ability of EE to regulate consumption during the initial stage of the addiction cycle. We have proposed that EE protective and therapeutic effects on binge-consumption of palatable substances might primarily be mediated by the modulatory control that EE exerts on anxiety and impulsivity/compulsivity traits, which are all risk factors favoring transition to drug addiction

Self-assembly of hexahistidine-tagged tobacco etch virus capsid protein into microfilaments that induce IgG2-specific response against a soluble porcine reproductive and respiratory syndrome virus chimeric protein

Antibody titers produced in sera of immunized mice recognizing His-TEV-CP protein. Immunization and ELISA procedures were conducted as described in Fig. 3 legend. Briefly explained, serum samples corresponding to bleeding 3 of mice group immunized with 25 μg of TEV VLPs (TEVVLPs25) were tested for total IgG and isotypes IgG1, IgG2a and IgG2b antibody response by ELISA in plates coated with with 1 μg of His-TEV-CP protein per well. Absorbance was taken at 450 nm in xMark spectrophotometer microplate reader (BioRad, USA). Results are expressed as antibody endpont titers greater than threefold the background value of preimmune sera. Excel was used for data processing. (TIFF 1142 kb

Environmental Enrichment During Adulthood Reduces Sucrose Binge-Like Intake in a High Drinking in the Dark Phenotype (HD) in C57BL/6J Mice

Repetitive binge episodes favor transition to binge-eating disorders. Experimental evidence points to positive influence of environmental enrichment (EE) on drug/food addiction, although far less is known regarding EE effects over binge-like consumption. Here, we evaluate the following: (1) whether switching from nonenriched standard environment (SE) to EE housing conditions during adulthood alters a stable pattern of voluntary sucrose (10% w/v) binge-like intake in high (HD) vs. low (LD) drinking phenotypes under a drinking in the dark (DID) schedule; and (2) sucrose binge-like intake in a DID task in response to a pharmacological challenge with an OXr1 antagonist in HD/LD subpopulations after long-term exposure to SE or EE conditions. Adolescent (postnatal day 21; PND21) mice were housed in SE conditions. At PND65, all animals were long-term exposed to sucrose DID. On the first episode of DID (PND65), animals were divided into HD vs. LD subpopulations according to their sucrose intake. On PND85, an OXr1 antagonist test was conducted on HD and LD mice with SB-334867 (SB) administration. On PND95, HD and LD subpopulations were again randomly allocated into two subgroups, resulting in the following experimental conditions: HD-SE, HD-EE, LD-SE and LD-EE. Sucrose binge-like intake continued until PND116, when a second SB test was conducted. The main findings are: (1) a single 2 h episode of sucrose binge drinking in a DID procedure consistently segregates two behavioral subpopulations, HD and LD; (2) when adult mice in standard conditions and long-term exposed to sucrose DID were switched to EE conditions, an immediate reduction in sucrose binge-like intake was observed in HD mice, pointing to a therapeutic role of EE exposure; and (3) administration of the OXr1 antagonist caused an acute reduction in sucrose binge-like intake in HD and LD mice exposed to SE conditions. Importantly, exposure to EE conditions blunted the inhibitory effect of SB on sucrose binge consumption in both behavioral phenotypes, indirectly suggesting a potential EE/OXr1 signaling interaction. We propose the hypothesis that EE might regulate OX-dependent anxiety/compulsivity brain systems, which might secondarily modulate sucrose binge-like intake

Environmental enrichment alleviates cognitive and psychomotor alterations and increases adult hippocampal neurogenesis in cocaine withdrawn mice

Cocaine is a widely used psychostimulant drug whose repeated exposure induces persistent cognitive/emotional dysregulation, which could be a predictor of relapse in users. However, there is scarce evidence on effective treatments to alleviate these symptoms. Environmental enrichment (EE) has been shown to be associated with improved synaptic function and cellular plasticity changes related to adult hippocampal neurogenesis (AHN), resulting in cognitive enhancement. Therefore, EE could mitigate the negative impact of chronic administration of cocaine in mice and reduce the emotional and cognitive symptoms present during cocaine abstinence. In this study, mice were chronically administered with cocaine for 14 days, and control mice received saline. After the last cocaine or saline dose, mice were submitted to control or EE housing conditions, and they stayed undisturbed for 28 days. Subsequently, mice were evaluated with a battery of behavioural tests for exploratory activity, emotional behaviour, and cognitive performance. EE attenuated hyperlocomotion, induced anxiolytic-like behaviour and alleviated cognitive impairment in spatial memory in the cocaine-abstinent mice. The EE protocol notably upregulated AHN in both control and cocaine-treated mice, though cocaine slightly reduced the number of immature neurons. Altogether, these results demonstrate that EE could enhance hippocampal neuroplasticity ameliorating the behavioural and cognitive consequences of repeated administration of cocaine. Therefore, environmental stimulation may be a useful strategy in the treatment cocaine addiction.This study was funded by the following grants: PSI2015-73,156-JIN to E.C-O. and PSI2017-82604R to L.J.S. (MINECO-AEI cofounded by FEDER), PID2020-114374RB-I00 (funded by MCIN/AEI/10.13039/501100011033) to E.C-O., PID2020-113806RB-I00 to L.J.S. (MICINN) and University of Malaga (B4: ‘Ayudas para Proyectos Puente’ to E. C–O). Authors M. C. M-P., P. T. and S. G-R. hold predoctoral grants from the Spanish Ministry of Science, Innovation and Universities (FPU17/00276 to M. C. M-P.; FPU18/00069 to P. T and FPU18/00941 to S. G-R.). The authors acknowledge the IBIMA's common research support structure of animal experimentation and behaviour (“Centro de Experimentación y Conducta Animal”; University of Malaga) and their staff for their valuable assistance during the behavioural experiments and maintenance of the mice and to Belén García and Carmen Hernández for their help with the confocal microscopy at the Cajal Institute // Funding for open access charge: Universidad de Málaga/CBUA

A novel tool for the evaluation and assessment of demand response activities in the industrial sector

This paper introduces a novel tool for industrial customers to perform a cost-benefit analysis regarding the implementation of Demand Response (DR) strategies in their facilities with the final goal of softening the impact of RES intermittency in the grid. The dynamic simulation tool focuses on assessing the participation of industries in reserve energy markets in the same conditions as generators offering capacity reserve, energy reserve or both of them and taking into account all the technical restrictions of production processes as well as possible extra costs due to the implementation of DR (additional labour cost, productivity losses, etc.) Main innovations of the methodology are the DR assessment carried out per process and the introduction of the margin of decision as a decision making strategy for the energy consumer. Along the paper, the methodology behind this tool is introduced step by step in order to show how the technical, economic and environmental analyses are performed. At the end, it is included the application of the methodology to a real paper factory in Germany. Results of the dynamic simulation tool are provided and discussed, showing the potential of the paper manufacturing in DR programmes as well as the benefits associated to it.This work was completed in the framework of the DRIP project (11ENV/DE/340) co-funded by the European Commission through the LIFE Environment Programme. The authors deeply thank all the participants in the project for their help and support that made possible this work.Rodríguez-García, J.; Álvarez, C.; Carbonell-Carretero, J.; Alcázar-Ortega, M.; Peñalvo López, E. (2016). A novel tool for the evaluation and assessment of demand response activities in the industrial sector. Energy. 113:1136-1146. doi:10.1016/j.energy.2016.07.146S1136114611

Cost-accuracy and patient experience assessment of blood pressure monitoring methods to diagnose hypertension: a comparative effectiveness study

Objectives: Studies of the diagnosis of hypertension have emphasized longterm cost-effectiveness analysis, but the patient experience and costs of blood pressure monitoring methods at the diagnosis stage remain unclear. We studied four diagnostic methods: a new 1 h-automated office blood pressure (BP) monitoring, office BP measurement, home BP monitoring, and awake-ambulatory BP monitoring. Methods: We carried out a comparative effectiveness study of four methods of diagnosing hypertension in 500 participants with a clinical suspicion of hypertension from three primary healthcare (PHC) centers in Barcelona city (Spain). We evaluated the time required and the intrinsic and extrinsic costs of the four methods. The cost-accuracy ratio was calculated and differences between methods were assessed using ANOVA and Tukey’s honestly significant difference (HSD) post-hoc test. Patient experience data were transformed using Rasch analysis and re-scaled from 0 to 10. Results: Office BP measurement was the most expensive method (€156.82, 95% CI: 156.18–157.46) and 1 h-automated BP measurement the cheapest (€85.91, 95% CI: 85.59–86.23). 1 h-automated BP measurement had the best cost-accuracy ratio (€ 1.19) and office BP measurement the worst (€ 2.34). Home BP monitoring (8.01, 95% CI: 7.70–8.22), and 1 h-automated BP measurement (7.99, 95% CI: 7.80–8.18) had the greatest patient approval: 66.94% of participants would recommend 1 h-automated BP measurement as the first or second option. Frontiers in Medicine 01 frontiersin.org González-de Paz et al. 10.3389/fmed.2022.827821 Conclusion: The relationship between the cost-accuracy ratio and the patient experience suggests physicians could use the new 1 h-automated BP measurement as the first option and awake-ambulatory BP monitoring in complicated cases and cease diagnosing hypertension using office BP measurement.This project received research grants from: The Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain), awarded on the 2016 call under the Health Strategy Action 2013–2016, within the National Research Program oriented to Societal Challenges, within the Technical, the Scientific and Innovation Research National Plan 2013–2016, with reference PI16/00660, co-funded with European Union ERDF funds (European Regional Development Fund). The Department of Health of the Generalitat de Catalunya, in the call corresponding to the year 2019 of the Strategic Plan of Research and Innovation in Health (PERIS) 2016–2020, with file code SLT008/18/00013.Peer ReviewedPostprint (published version

Análisis De Programas De Promoción De La Salud En Jóvenes Basados En Evidencia Desde El PYD

Objective: Analyze health promotion programs based on the perspective of Positive Youth Development (PYD) to identify characteristics, advantages and limitations in order to promote health and prevent substance use. Method and procedure: Bibliographic research was used, analyzing 37 intervention programs, specifically focused on the area of substance abuse. Results: The main categories analyzed relate to the objective of preventing the consumption and / or abuse of substances, an average duration of 15 sessions, working with adolescent population, taught by teachers and parents previously trained, using questionnaires, interviews and scales as evaluation methods, based on an experimental and quasi-experimental design, within family, school and community context components, resulting in the prevention of substance use, better school performance and the development of lifetime skills. Conclusions: This type of analysis allows us to identify, guide and organize the information obtained from each program that uses the PYD model and that has been analyzed in detail, with the purpose of contributing to the development of a program to promote healthy development in the Mexican population

Associations of dietary energy density with body composition and cardiometabolic risk in children with overweight and obesity: role of energy density calculations, under-reporting energy intake and physical activity

This study examined (1) the association of dietary energy density from solid (EDS) and solid plus liquids (EDSL) with adiposity and cardiometabolic risk factors (CRF) in children with overweight and obesity, (2) the effect of under-reporting on the mentioned associations and (3) whether the association between ED and body composition and CRF is influenced by levels of physical activity. In a cross-sectional design, 208 overweight and obese children (8-12-year-old; 111 boys) completed two non-consecutive 24 h recalls. ED was calculated using two different approaches: EDS and EDSL. Under-reporters were determined with the Goldberg method. Body composition, anthropometry and fasting blood sample measurements were performed. Moderate to vigorous physical activity (MVPA) was registered with accelerometers (7-d-register). Linear regressions were performed to evaluate the association of ED with the previously mentioned variables. Neither EDS nor EDSL were associated with body composition or CRF. However, when under-reporters were excluded, EDS was positively associated with BMI (P=0 019), body fat percentage (P=0 005), abdominal fat (P=0 008) and fat mass index (P=0 018), while EDSL was positively associated with body fat percentage (P=0 008) and fat mass index (P=0 026). When stratifying the group according to physical activity recommendations, the aforementioned associations were only maintained for non-compliers. Cluster analysis showed that the low-ED and high-MVPA group presented the healthiest profile for all adiposity and CRF. These findings could partly explain inconsistencies in literature, as we found that different ED calculations entail distinct results. Physical activity levels and excluding under-reporters greatly influence the associations between ED and adiposity in children with overweight and obesity.The research leading to these results has received funding from la Caixa Foundation and Triptolemos Foundation, the Ministry of Health (FIS PI081297), the Research Network on Preventative Activities and Health Promotion (RD06/0018/ 0038), the Henning and Johan Throne-Holst Foundation (F. B. O.), the Spanish Ministry of Education, Culture and Sport (FPU14/03329 to M. M.), the Spanish Ministry of Economy and Competitiveness (DEP2013-47540 and DEP2016-78377-R; BES-2014-068829 to C. C.-S.), Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01335), Fondos Estructurales de la Union Europea (FEDER), Una manera de hacer Europa, the Spanish Ministry of Science and Innovation (RYC-2011-09011 to F. B. O.), the University of Granada, Plan Propio de Investigacion 2016, Excellence Actions: Units of Excellence, Unit of Excellence on Exercise and Health (UCEES), Programa de Captacion de Talento - UGR Fellows (L. G.-M.), the SAMID III network, RETICS (PN I +D+ I 2017-2021). This study has been partially funded by the University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES), and by the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades and European Regional Development Fund (ERDF), reference SOMM17/6107/UGR. ISCIII-Sub-Directorate General for Research Assessment and Promotion, the European Regional Development Fund (RD16/ 0022), the EXERNET Research Network on Exercise and Health in Special Populations (DEP2005-00046/ACTI), and the University of the Basque Country (GIU14/21). J. M.-G. is supported by the Spanish Ministry of Education, Culture and Sport (FPU14/06837). J. H. M. is supported by the Spanish Ministry of Education, Culture and Sport (FPU15/02645)

GABAergic deficits in absence of LPA1 receptor, associated anxiety-like and coping behaviors, and amelioration by interneuron precursor transplants into the dorsal hippocampus

Defects in GABAergic function can cause anxiety- and depression-like behaviors among other neuropsychiatric disorders. Therapeutic strategies using the transplantation of GABAergic interneuron progenitors derived from the medial ganglionic eminence (MGE) into the adult hippocampus reversed the symptomatology in multiple rodent models of interneuron-related pathologies. In turn, the lysophosphatidic acid receptor LPA has been reported to be essential for hippocampal function. Converging evidence suggests that deficits in LPA receptor signaling represent a core feature underlying comparable hippocampal dysfunction and behaviors manifested in common neuropsychiatric conditions. Here, we first analyzed the GABAergic interneurons in the hippocampus of wild-type and maLPA-null mice, lacking the LPA receptor. Our data revealed a reduction in the number of neurons expressing GABA, calcium-binding proteins, and neuropeptides such as somatostatin and neuropeptide Y in the hippocampus of maLPA-null mice. Then, we used interneuron precursor transplants to test links between hippocampal GABAergic interneuron deficit, cell-based therapy, and LPA receptor-dependent psychiatric disease-like phenotypes. For this purpose, we transplanted MGE-derived interneuron precursors into the adult hippocampus of maLPA-null mice, to test their effects on GABAergic deficit and behavioral symptoms associated with the absence of the LPA receptor. Transplant studies in maLPA-null mice showed that grafted cells were able to restore the hippocampal host environment, decrease the anxiety-like behaviors and neutralize passive coping, with no abnormal effects on motor activity. Furthermore, grafted MGE-derived cells maintained their normal differentiation program. These findings reinforce the use of cell-based strategies for brain disorders and suggest that the LPA receptor represents a potential target for interneuron-related neuropsychiatric disorders.This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities, co-funded by the European Regional Development Fund (ERDF, EU), (PSI2017-82604R, to LJS; PSI2017-83408-P to CP; SAF09-07746, to MAD; PI16/01510, to GET) and Andalusian Regional Ministries of Economy, Knowledge, Business and University (SEJ-4515 -to LJS; SEJ1863 to CP) and of Health and Families (Nicolas Monardes Programme to GET)