Inhibiting CRF Projections from the Central Amygdala to Lateral Hypothalamus and Amygdala Deletion of CRF Alters Binge-Like Ethanol Drinking in a Sex-Dependent Manner.

Background: Binge alcohol drinking is a dangerous pattern of consumption that can contribute to the development of more severe alcohol use disorders (AUDs). Importantly, the rate and severity of AUDs has historically differed between men and women, suggesting that there may be sex differences in the central mechanisms that modulate alcohol (ethanol) consumption. Corticotropin releasing factor (CRF) is a centrally expressed neuropeptide that has been implicated in the modulation of binge-like ethanol intake, and emerging data highlight sex differences in central CRF systems. Methods: In the present report we characterized CRF+ neurocircuitry arising from the central nucleus of the amygdala (CeA) and innervating the lateral hypothalamus (LH) in the modulation of binge-like ethanol intake in male and female mice. Results: Using chemogenetic tools we found that silencing the CRF+ CeA to LH circuit significantly blunted binge-like ethanol intake in male, but not female, mice. Consistently, genetic deletion of CRF from neurons of the CeA blunted ethanol intake exclusively in male mice. Furthermore, pharmacological blockade of the CRF type-1 receptor (CRF1R) in the LH significantly reduced binge-like ethanol intake in male mice only, while CRF2R activation in the LH failed to alter ethanol intake in either sex. Finally, a history of binge-like ethanol drinking blunted CRF mRNA in the CeA regardless of sex. Conclusions: These observations provide novel evidence that CRF+ CeA to LH neurocircuitry modulates binge-like ethanol intake in male, but not female mice, which may provide insight into the mechanisms that guide known sex differences in binge-like ethanol intake.

The Effect of Very-Long-Chain n-3 Polyunsaturated Fatty Acids in the Central Nervous System and Their Potential Benefits for Treating Alcohol Use Disorder: Reviewing Pre-Clinical and Clinical Data.

Alcohol use poses a significant global health concern, leading to serious physical and socioeconomic issues worldwide. The current treatment options for problematic alcohol consumption are limited, leading to the exploration of alternative approaches, such as nutraceuticals. One promising target is very-long-chain n-3 polyunsaturated fatty acids (VLC n-3 PUFAs). This review aims to compile the most relevant pre-clinical and clinical evidence on the effect of VLC n-3 PUFAs on alcohol use disorders and related outcomes. The findings suggest that VLC n-3 PUFAs may alleviate the physiological changes induced by alcohol consumption, including neuroinflammation and neurotransmitter dysregulation. Additionally, they can reduce withdrawal symptoms, improve mood, and reduce stress level, all of which are closely associated with problematic alcohol consumption. However, more research is required to fully understand the precise mechanisms by which VLC n-3 PUFAs exert their function. Furthermore, PUFAs should not be considered a standalone solution, but as a complement to other therapeutic approaches. Although preliminary evidence supports the potential therapeutic effect of VLC n-3 PUFAs on problematic alcohol consumption, additional research is needed to validate these findings and determine the optimal use of PUFAs as part of a comprehensive approach to the treatment of alcohol use disorders.

Effects of probiotics on cognitive and emotional functions in healthy older adults: Protocol for a double-blind randomized placebo-controlled crossover trial.

Aging is a process that includes changes in cognitive and emotional functions, as well as changes in the diversity and integrity of gut microbiota. Probiotic treatments have recently been studied as a potential new therapeutic approach to alleviate a wide range of problems in other populations; however, clinical studies in older adults remain insufficient and limited. Thus, the aim of this project is to evaluate the efficacy of a multispecies probiotic formulation as a therapeutic strategy for attenuating the emotional and cognitive decline associated with aging in adults over the age of 55. This is a double-blind randomized placebo-controlled crossover trial involving at least 32 older adults and comparing two conditions: (a) probiotic, providing a multispecies probiotic for 10 weeks (Lactobacillus rhamnosus and Bifidobacterium lactis); and (b) placebo, receiving a harmless substance (potato starch). Despite the increasing use of probiotics for the treatment of cognitive and emotional problems, no study has yet focused on this group, to the best of our knowledge. Therapeutic strategies of the kind outlined in this protocol will help to shed light on the current state of knowledge about this topic, as well as promote health programs tailored to this population, which would encourage active aging and healthy lifestyles. Not only do we expect improvements in the emotional dimension in terms of anxiety, stress, depression, and sleep quality, we also expect improvements in the cognitive dimension in terms of attention, memory, and decreased impulsivity.

The melanocortin system as a potential target for treating alcohol use disorders: A review of pre-clinical data.

The melanocortin (MC) system consists of neuropeptides that are cleaved from the polypeptide precursor proopiomelanocortin (POMC). In the brain, MC neuropeptides signal primarily through the MC-3 and MC-4 receptors, which are widely expressed throughout the brain. While the MC system has been largely studied for its role in food intake and body weight regulation, converging evidence has emerged over approximately the last 20-years showing that alcohol (ethanol), and other drugs of abuse influence the central MC system, and that manipulating MC receptor signalling modulates ethanol intake. Although there is divergent evidence, the wealth of data appears to suggest that activating MC signalling, primarily through the MC-4 receptor, is protective against excessive ethanol consumption. In the present review, we first describe the MC system and then detail how ethanol exposure and consumption alters central MC and MC-receptor expression and levels. This is followed by a review of the data, from pharmacological and genetic studies, which show that manipulations of MC receptor activity alter ethanol intake. We then briefly highlight studies implicating a role for the MC system in modulating neurobiological responses and intake of other drugs of abuse, including amphetamine, cocaine and opioids. Finally, we introduce relatively new observations that the drug, bupropion (BUP), a drug that activates central MC activity, significantly reduces ethanol intake in rodent models when administered alone and in combination with the non-selective opioid receptor antagonist, naltrexone. Phase II clinical trials are currently underway to assess the efficacy of BUP as a treatment for alcohol use disorders.

Microbiota and organophosphates.

Organophosphates (OPs) are important toxic compounds commonly used for a variety of purposes in agriculture, industry and household settings. Consumption of these compounds affects several central nervous system functions. Some of the most recognised consequences of organophosphate pesticide exposure in humans include neonatal developmental abnormalities, endocrine disruption, neurodegeneration, neuroinflammation and cancer. In addition, neurobehavioral and emotional deficits following OP exposure have been reported. It would be of great value to discover a therapeutic strategy which produces a protective effect against these neurotoxic compounds. Moreover, a growing body of preclinical data suggests that the microbiota may affect metabolism and neurotoxic outcomes through exposure to OPs. The human gut is colonised by a broad variety of microorganisms. This huge number of bacteria and other microorganisms which survive by colonising the gastrointestinal tract is defined as "gut microbiota". The gut microbiome plays a profound role in metabolic processing, energy production, immune and cognitive development and homeostasis. The effects are not only localized in the gut, but also influence many other organs, such as the brain through the microbiome-gut-brain axis. Therefore, given the gut microbiota's key role in host homeostasis, this microbiota may be altered or modified temporarily by factors such as antibiotics, diet and toxins such as pesticides. The aim of this review is to examine scientific articles concerning the impact of microbiota in OP toxicity. Studies focussed on the possible contribution the microbiota has on variable host pharmacokinetic responses such as absorption and biotransformation of xenobiotics will be evaluated. Microbiome manipulation by antibiotic or probiotic administration and faecal transplantation are experimental approaches recently proposed as treatments for several diseases. Finally, microbiota manipulation as a possible therapeutic strategy in order to reduce OP toxicity will be discussed.

Creencias sobre salud y prácticas de autocuidado en adultos jóvenes: estudio biográfico de estilos de vida / Beliefs on health and self-care practices in young adults: biographical study of lifestyles / Crenças sobre saúde e práticas de autocuidado em adultos jóvens: estudo biográfico de estilos de vida

Resumen El abundante acceso a información y recomendaciones para el autocuidado de la salud a través de los medios de comunicación y los programas de salud pública no han logrado aumentar la adherencia de la población a estilos de vida saludables. A pesar de los avances en esta materia, las enfermedades no trasmisibles asociadas a estilos de vida insanos siguen siendo una epidemia a nivel mundial. Objetivo: Para comprender uno de los factores psicosociales relevantes para el autocuidado de la salud se estudió en profundidad las creencias de profesionales jóvenes chilenos sobre salud y sobre sus prácticas de autocuidado. Materiales y métodos: Mediante un estudio cualitativo basado en el paradigma fenomenológico y el método biográfico se analizó las historias de vida de 14 adultos jóvenes profesionales que trabajan en distintas áreas laborales. Resultado: En base a un análisis de contenido se muestra que los jóvenes manifiestan creencias favorables hacia un estilo de vida saludable, pero a nivel de sus prácticas de autocuidado ellos mantienen algunas conductas no saludables. Es así como, independientemente del conocimiento científico que manejan sobre salud, los jóvenes generan una estructura argumentativa personal que les permite autojustificar la inconsistencia entre sus creencias y sus prácticas de autocuidado. Conclusiones: Estos hallazgos plantean la necesidad de redirigir el foco de las intervenciones de promoción de estilos de vida saludables.

Abstract The abundant access to information and recommendations for self-care for health through the media and public health programs have not managed to increase the adherence of the population to healthy lifestyles. Despite advances in this area, the non-communicable diseases associated with unhealthy lifestyles continue to be an epidemic worldwide. Objective: the beliefs of Chilean young professionals about health and self-care were studied in depth to understand one of the relevant psychosocial factors that affect health self-care. Materials and methods: through a qualitative study based on the phenomenological paradigm and the biographical method, the life stories of 14 Chilean young professional adults working in different work areas were analyzed. Results: based on a content analysis, young people show favorable beliefs towards a healthy lifestyle but, at the level of self-care practices, they maintain some unhealthy behaviors. This is how, reagardless of the scientific knowledge they handle about health, young people generate a personal argumentative structure that allows them to selfjustify the inconsistence between their beliefs and their self-care practices. Conclusions: These findings raise the need to redirect the focus of interventions promoting healthy lifestyles.

Resumo O abundante aceso a informação e recomendações para o autocuidado da saúde a través dos meios de comunicação e os programas de saúde pública não tem logrado aumentar a aderência da povoação a estilos de vida saudáveis. A pesar dos avanços nesta matéria, as doenças não transmissíveis associadas a estilos de vida insanos seguem sendo uma epidemia a nível mundial. Objetivo: Para compreender um dos fatores psicossociais relevantes para o autocuidado da saúde se estudou em profundidade as crenças de professionais jovens chilenos sobre saúde e sobre suas práticas de autocuidado. Materiais e métodos: Através dum estudo qualitativo baseado no paradigma fenomenológico e o método biográfico se analisou as histórias de vida de 14 adultos jovens profissionais que trabalham em diferentes áreas ocupacionais. Resultado: De acordo a uma análise de conteúdo se amostra que os jovens manifestam crenças favoráveis para um estilo de vida saudável, mas a nível de suas práticas de autocuidado eles mantem algumas condutas não saudáveis. É assim como, independentemente do conhecimento científico que têm sobre saúde, os jovens geram uma estrutura argumentativa pessoal que lhes permite auto justificar a inconsistência entre suas crenças e suas práticas de autocuidado. Conclusões: Estas descobertas estabelecem a necessidade de redirecionar o foco das intervenções de promoção de estilos de vida saudáveis.

Emotional Reactivity to Incentive Downshift in Adult Rats Exposed to Binge-Like Ethanol Exposure During Adolescence.

Alcohol use in adolescents is often characterized by binge-like ethanol consumption pattern, which is associated with long-term health consequences and even with important harms to his developing brain. Among this, ethanol exposure induces long-lasting alterations in anxiety-related neurobiological systems such as corticotropin releasing factor (CRF) or melanocortin system (MC). Recently, it has been demonstrated that adult rats exposed to adolescent intermittent ethanol (AIE) exposure exhibited anxiogenic-like behavior. Given that it has been demonstrated that negative affective state is relevant to development of addictive behavior, it is tempting to suggest that increased risk of adult abusive alcohol use exhibited in rats exposed to ethanol during adolescence may be related with differences in anxiety-related behavior. We conducted a study investigating the emotional reactivity after a reward devaluation (12-to-1 pellet or 32-to-4% sucrose downshift) in adult rats exposed to binge-like ethanol exposure during adolescence. For this aim, adolescent Sprague-Dawley rats were treated with ethanol (2.5 g/kg ip; AIE) or saline (AIS) for 2 consecutive days at 48-h intervals over a 14-day period (PND30-PND43). Following 25 free-ethanol days, adult rats were trained in consummatory and instrumental successive negative contrast task (cSNC and iSNC). Our data shows that both AIE and AIS groups exhibited suppression of the consummatory and instrumental behavior after reward devaluation relative to unshifthed control. Also, adult rats exposed to alcohol during adolescence exhibited a particularly strong negative affective state (lower sucrose consumption) with regards to the AIS group in the cSNC. This data demonstrated that adolescent binge-like ethanol exposure might trigger a greater emotional reactivity following incentive downshift, which might be linked to higher vulnerability to substance use disorder.

[Frailty in older adults with type 2 diabetes mellitus and its relation with glucemic control, lipid profile, blood pressure, balance, disability grade and nutritional status]. / Fragilidad en el adulto mayor con diabetes mellitus tipo 2 y su relación con el control glucémico, perfil lipídico, tensión arterial, equilibrio, grado de discapacidad y estado nutricional.

INTRODUCTION: frailty identifies a subgroup of people with higher risk of morbidity and mortality. AIMS: our first aim was to determine the prevalence of frailty in older adults with type 2 diabetes mellitus; our second aim was to establish which factors are associated with frailty in these patients. MATERIAL AND METHODS: cross-sectional study in non-institutionalized people (288 patients), over 65 years of age, and diagnosed with diabetes mellitus type 2. Frailty was defined according to Freid's criteria. The following variables were assessed: blood pressure, glycosylated hemoglobin, total cholesterol, HDL and LDL cholesterol, triglycerides, Lawton and Brody index, balance through unipodal support, and nutritional status by using the Mini Nutritional Assessment questionnaire. RESULTS: the prevalence of frailty syndrome was 14.6%. The frailty group showed lower systolic blood pressure (p < 0.001), higher triglycerides levels (p = 0.007), and lower Lawton and Brody values (p < 0.001) than the non-frailty one; moreover, lower monopodal balance was observed with higher frailty levels (r = -0.306, p < 0.001). None frailty-subject was able to perform five seconds or more in balance (r = -0.343, p < 0.001). Moreover, higher frailty was related with poorer Mini Nutritional Assessment results (p = 0.013). CONCLUSION: the prevalence of frailty syndrome in patients with diabetes was higher compared with those in general population over 65 years of age. Frailty was related to lower systolic blood pressure, higher triglycerides concentrations, poorer nutritional status, and lower independency to perform instrumental activities of daily living and poorer balance.

Introducción: la fragilidad identifica a un subgrupo de personas con mayor riesgo de morbimortalidad.Objetivos: determinar la prevalencia de fragilidad y qué factores se asocian a esta en los pacientes adultos mayores con diabetes mellitus tipo 2.Material y métodos: estudio transversal en población residente no institucionalizada (288 pacientes), mayores de 65 años, diagnosticados de diabetes mellitus tipo 2. La fragilidad se define mediante los criterios de Freid. Se valoraron tensión arterial, hemoglobina glicosilada, colesterol total, HDL y LDL, triglicéridos, índice de Lawton y Brody, equilibrio mediante el apoyo unipodal y estado nutricional mediante el Mini Nutritional Assessment.Resultados: la prevalencia encontrada del síndrome de fragilidad fue del 14,6%. El grupo frágil tuvo niveles de tensión arterial sistólica más bajos (p < 0,001), los triglicéridos estaban más elevados (p = 0,007) y obtuvieron valores inferiores en Lawton y Brody (p < 0,001) respecto al grupo no frágil; además, el test de equilibrio monopodal ofreció tiempos menores con la fragilidad (r = -0,306, p < 0,001). Ninguno de los sujetos frágiles aguantó en equilibrio cinco segundos o más (r = -0,343, p < 0,001). Los valores del Mini Nutritional Assessment empeoraron con la fragilidad (p = 0,013).Conclusión: la prevalencia del síndrome de fragilidad en pacientes diabéticos fue mayor a la encontrada en población general mayor de 65 años. La fragilidad se asocia a una disminución de la tensión arterial sistólica, cifras de triglicéridos mayores, peor estado nutricional y disminución de la independencia para la realización de las actividades instrumentales de la vida diaria y peor equilibrio.

Fragilidad en el adulto mayor con diabetes mellitus tipo 2 y su relación con el control glucémico, perfil lipídico, tensión arterial, equilibrio, grado de discapacidad y estado nutricional / Frailty in older adults with type 2 diabetes mellitus and its relation with glucemic control, lipid profile, blood pressure, balance, disability grade and nutritional status

Introducción: la fragilidad identifica a un subgrupo de personas con mayor riesgo de morbimortalidad. Objetivos: determinar la prevalencia de fragilidad y qué factores se asocian a esta en los pacientes adultos mayores con diabetes mellitus tipo 2.Material y métodos: estudio transversal en población residente no institucionalizada (288 pacientes), mayores de 65 años, diagnosticados de diabetes mellitus tipo 2. La fragilidad se define mediante los criterios de Freid. Se valoraron tensión arterial, hemoglobina glicosilada, colesterol total, HDL y LDL, triglicéridos, índice de Lawton y Brody, equilibrio mediante el apoyo unipodal y estado nutricional mediante el Mini Nutritional Assessment. Resultados: la prevalencia encontrada del síndrome de fragilidad fue del 14,6%. El grupo frágil tuvo niveles de tensión arterial sistólica más bajos (p < 0,001), los triglicéridos estaban más elevados (p = 0,007) y obtuvieron valores inferiores en Lawton y Brody (p < 0,001) respecto al grupo no frágil; además, el test de equilibrio monopodal ofreció tiempos menores con la fragilidad (r = -0,306, p < 0,001). Ninguno de los sujetos frágiles aguantó en equilibrio cinco segundos o más (r = -0,343, p < 0,001). Los valores del Mini Nutritional Assessment empeoraron con la fragilidad (p = 0,013).Conclusión: la prevalencia del síndrome de fragilidad en pacientes diabéticos fue mayor a la encontrada en población general mayor de 65 años. La fragilidad se asocia a una disminución de la tensión arterial sistólica, cifras de triglicéridos mayores, peor estado nutricional y disminución de la independencia para la realización de las actividades instrumentales de la vida diaria y peor equilibrio

Introduction: frailty identifies a subgroup of people with higher risk of morbidity and mortality. Aims: our first aim was to determine the prevalence of frailty in older adults with type 2 diabetes mellitus; our second aim was to establish which factors are associated with frailty in these patients. Material and methods: cross-sectional study in non-institutionalized people (288 patients), over 65 years of age, and diagnosed with diabetes mellitus type 2. Frailty was defined according to Freid's criteria. The following variables were assessed: blood pressure, glycosylated hemoglobin, total cholesterol, HDL and LDL cholesterol, triglycerides, Lawton and Brody index, balance through unipodal support, and nutritional status by using the Mini Nutritional Assessment questionnaire. Results: the prevalence of frailty syndrome was 14.6%. The frailty group showed lower systolic blood pressure (p < 0.001), higher triglycerides levels (p = 0.007), and lower Lawton and Brody values (p < 0.001) than the non-frailty one; moreover, lower monopodal balance was observed with higher frailty levels (r = -0.306, p < 0.001). None frailty-subject was able to perform five seconds or more in balance (r = -0.343, p < 0.001). Moreover, higher frailty was related with poorer Mini Nutritional Assessment results (p = 0.013). Conclusion: the prevalence of frailty syndrome in patients with diabetes was higher compared with those in general population over 65 years of age. Frailty was related to lower systolic blood pressure, higher triglycerides concentrations, poorer nutritional status, and lower independency to perform instrumental activities of daily living and poorer balance

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.

[Relationship between quality of life, physical activity, nutrition, glycemic control and sarcopenia in older adults with type 2 diabetes mellitus]. / Relación entre calidad de vida, actividad física, alimentación y control glucémico con la sarcopenia de adultos mayores con diabetes mellitus tipo 2.

INTRODUCTION: The term sarcopenia is defined as age-related loss of skeletal muscle mass and function, with a consequent impact on quality of life. However, there is a lack of studies examining the prevalence of sarcopenia in patients with type 2 diabetes mellitus (DM). OBJECTIVES: To analyze the prevalence of sarcopenia in patients over 65 years with type 2 DM and the influence of physical activity, diet, glycemic control, sex, age, and quality of life. METHODS: A total of 279 patients (155 females), aged 76.6 ± 6.27 years, participated in this study in order to analyze body circumferences (waist, hip, calf, and arm), body mass index, handgrip strength, physical activity level, nutritional status, quality of life, and glycemic control. The cut-off value for sarcopenia was defined as the body mass index lower than 9.2 or 7.4 kg/m2 for males and females, respectively. RESULTS: In participants, the prevalence of sarcopenia was 8.33%. Moreover, the level of sarcopenia was negatively associated with quality of life (r = -0.130, p = 0.030), physical activity (r = -0.164, p = 0.006), nutritional status (r = -0.274, p < 0.001), and male sex (r = -0.137, p = 0.022); and positively associated with age (r = 0.183, p = 0.002). CONCLUSIONS: The prevalence of sarcopenia in patients with type 2 DM is moderate, and it is related to relevant health factors, such as lower quality of life, lower physical exercise level, and increased malnutrition, especially in older adult males.

Relación entre calidad de vida, actividad física, alimentación y control glucémico con la sarcopenia de adultos mayores con diabetes mellitus tipo 2 / Relationship between quality of life, physical activity, nutrition, glycemic control and sarcopenia in older adults with type 2 diabetes mellitus

Introducción: la sarcopenia se define como la pérdida de masa muscular y su deterioro funcional asociado a la edad, por lo que tiene un alto impacto sobre la calidad de vida. Sin embargo, la prevalencia de la sarcopenia en diabetes mellitus tipo 2 (DM2) no está suficientemente estudiada. Objetivos: analizar la prevalencia de sarcopenia en mayores de 65 años con DM2 y la posible influencia de la actividad física, la alimentación, el control glucémico, el sexo, la edad y la calidad de vida. Métodos: participaron 279 pacientes (155 mujeres) de 76,6 ± 6,27 años de edad. Se determinó el perímetro de cintura, cadera, pantorrilla y brazo, el índice de masa corporal, la fuerza de prensión manual, el nivel de actividad física, el estado nutricional, la calidad de vida y el control glucémico. La sarcopenia se definió como un índice de masa muscular esquelética menor de 9,2 kg/m2 en varones y menor de 7,4 kg/m2 en mujeres. Resultados: la prevalencia de sarcopenia en los participantes fue de un 8,33%. Hubo asociación negativa entre el nivel de sarcopenia y la calidad de vida (r = -0,130, p = 0,030), actividad física (r = -0,164, p = 0,006), estado nutricional (r = -0,274, p < 0,001), y sexo masculino (r = -0,137, p = 0,022); y positiva para edad (r = 0,183, p = 0,002). Conclusiones: la prevalencia de la sarcopenia en DM2 es moderada. Se relaciona con importantes factores para la salud, como una menor calidad de vida, menor realización de ejercicio físico y mayor presencia de desnutrición, lo cual parece agravarse en adultos varones de edad avanzada (AU)

Introduction: The term sarcopenia is defined as age-related loss of skeletal muscle mass and function, with a consequent impact on quality of life. However, there is a lack of studies examining the prevalence of sarcopenia in patients with type 2 diabetes mellitus (DM). Objectives: To analyze the prevalence of sarcopenia in patients over 65 years with type 2 DM and the influence of physical activity, diet, glycemic control, sex, age, and quality of life. Methods: A total of 279 patients (155 females), aged 76.6 ± 6.27 years, participated in this study in order to analyze body circumferences (waist, hip, calf, and arm), body mass index, handgrip strength, physical activity level, nutritional status, quality of life, and glycemic control. The cut-off value for sarcopenia was defined as the body mass index lower than 9.2 or 7.4 kg/m2 for males and females, respectively. Results: In participants, the prevalence of sarcopenia was 8.33%. Moreover, the level of sarcopenia was negatively associated with quality of life (r = -0.130, p = 0.030), physical activity (r = -0.164, p = 0.006), nutritional status (r = -0.274, p < 0.001), and male sex (r = -0.137, p = 0.022); and positively associated with age (r = 0.183, p = 0.002). Conclusions: The prevalence of sarcopenia in patients with type 2 DM is moderate, and it is related to relevant health factors, such as lower quality of life, lower physical exercise level, and increased malnutrition, especially in older adult males (AU)

Nucleus Accumbens MC4-R Stimulation Reduces Food and Ethanol Intake in Adult Rats Regardless of Binge-Like Ethanol Exposure during Adolescence.

The melanocortin (MC) system regulates feeding and ethanol consumption. Recent evidence shows that melanocortin 4 receptor (MC4-R) stimulation within the nucleus accumbens (NAc) elicits anorectic responses and reduces ethanol consumption and ethanol palatability in adult rats. Ethanol exposure during adolescence causes long-lasting changes in neural pathways critically involved in neurobehavioral responses to ethanol. In this regard, binge-like ethanol exposure during adolescence reduces basal alpha-melanocyte-stimulating hormone (α-MSH) and alters the levels of agouti-related peptide (AgRP) in hypothalamic and limbic areas. Given the protective role of MC against excessive ethanol consumption, disturbances in the MC system induced by binge-like ethanol exposure during adolescence might contribute to excessive ethanol consumption during adulthood. In the present study, we evaluated whether binge-like ethanol exposure during adolescence leads to elevated ethanol intake and/or eating disturbance during adulthood. Toward that aim, Sprague-Dawley rats were treated with ethanol (3 g/kg i.p.; BEP group) or saline (SP group) for 14 days (PND 25 to PND 38). On PND73, all the groups were given access to 20% ethanol on an intermittent schedule. Our results showed that adult rats given intermittent access (IAE) to 20% ethanol achieved high spontaneous ethanol intake that was not significantly enhanced by binge-like ethanol pretreatment during adolescence. However, BEP group exhibited an increase in food intake without a parallel increase in body weight (BW) relative to SP group suggesting caloric efficiency disturbance. Additionally, we evaluated whether binge-like ethanol exposure during adolescence alters the expected reduction in feeding and ethanol consumption following NAc shell administration of a selective MC4-R agonist in adult rats showing high rates of ethanol consumption. For that, animals in each pretreatment condition (SP and BEP) were divided into three subgroups and given bilateral NAc infusions of the selective MC4-R agonist cyclo(NH-CH2-CH2-CO-His-D-Phe-Arg-Trp-Glu)-NH2 (0, 0.75 or 1.5 µg). Results revealed that MC4-R stimulation within the NAc reduced feeding and ethanol intake in high ethanol-drinking adult rats, regardless of previous binge-like ethanol exposure during adolescence, which adds new evidence regarding the dual ability of MC compounds to control excessive ethanol and food intake.

Evidence that Melanocortin Receptor Agonist Melanotan-II Synergistically Augments the Ability of Naltrexone to Blunt Binge-Like Ethanol Intake in Male C57BL/6J Mice.

BACKGROUND: The nonselective opioid receptor antagonist, naltrexone (NAL), reduces alcohol (ethanol [EtOH]) consumption in animals and humans and is an approved medication for treating alcohol abuse disorders. Proopiomelanocortin (POMC)-derived melanocortin (MC) and opioid peptides are produced in the same neurons in the brain, and recent preclinical evidence shows that MC receptor (MCR) agonists reduce excessive EtOH drinking in animal models. Interestingly, there is a growing body of literature revealing interactions between the MC and the opioid systems in the modulation of pain, drug tolerance, and food intake. METHODS: In the present report, a mouse model of binge EtOH drinking was employed to determine whether the MCR agonist, melanotan-II (MTII), would improve the effectiveness of NAL in reducing excessive binge-like EtOH drinking when these drugs were co-administered prior to EtOH access. RESULTS: Both NAL and MTII blunt binge-like EtOH drinking and associated blood EtOH levels, and when administered together, a low dose of MTII (0.26 mg/kg) produces a 7.6-fold increase in the effectiveness of NAL in reducing binge-like EtOH drinking. Using isobolographic analysis, it is demonstrated that MTII increases the effectiveness of NAL in a synergistic manner. CONCLUSIONS: The current observations suggest that activators of MC signaling may represent a new approach to treating alcohol abuse disorders and a way to potentially improve existing NAL-based therapies.

Orexin receptor 1 signaling contributes to ethanol binge-like drinking: Pharmacological and molecular evidence.

Orexins (OX) have been recently implicated in ethanol seeking and self-administration. A few recent studies have provided additional evidence that OX receptor antagonists effectively reduce voluntary ethanol consumption in subjects spontaneously showing high levels of ethanol intake. The present study further evaluates the contribution of OXR1 to excessive binge-like drinking of ethanol in ad libitum-fed C57BL/6J mice from a pharmacological and molecular approach. The main findings in the study are: (1) Icv administration of SB-334867 (3 µg/µl) blunted ethanol (20% v/v), but not saccharin (0.15% w/v) binge-like drinking in a drinking in the dark procedure, without any alteration of chow consumption or total calories ingested; (2) Icv administration of SB-334867 (3 µg/µl) increased the latency to recover the righting reflex after a sedative dose of ethanol without any significant alteration in ethanol peripheral metabolism; (3) four repetitive, 2-h daily episodes of saccharin, but not ethanol binge-like drinking blunted OXR1 mRNA expression in the lateral hypothalamus. Present findings extend the current knowledge pointing to a role for OX signaling in ethanol sedation, which might partially explain the inhibitory effect of OXR1 antagonists on ethanol consumption. Combined pharmacological and molecular data suggesting the contribution of OXR1 in ethanol binge-drinking leading us to propose the idea that targeting OXR1 could represent a novel pharmacological approach to control binge-consumption episodes of ethanol in vulnerable organisms failing to spontaneously reduce OX activity.

Polymorphism in the corticotropin-releasing factor receptor 1 (CRF1-R) gene plays a role in shaping the high anxious phenotype of Marchigian Sardinian alcohol-preferring (msP) rats.

INTRODUCTION: Marchigian Sardinian alcohol-preferring (msP) rats exhibit innate preference for alcohol along with anxious phenotype. In these animals, two single-nucleotide polymorphisms in position -1,836 and -2,097 from the first start codon of the CRF1-R transcript have been found. MATERIALS AND METHODS: Here, we examined whether these point mutations account for the heightened anxiety-like behavior and stress responsiveness of msP rats. We rederived the msP rats to obtain two distinct lines carrying the wild-type (GG) and point mutations (AA), respectively. RESULTS: CRF1-R gene expression analysis revealed significant dysregulation of the system in the extended amygdala of AA rats. At the behavioral level, using the elevated plus maze, we found that both AA and GG lines had higher basal anxiety compared to Wistar rats. In the defensive burying test, AA rats showed decreased burying behavior compared to the GG and the unselected Wistar lines. Freezing/immobility did not differ among AA and GG but was higher than that of Wistars. The selective CRF1-R antagonist antalarmin (0, 10, and 20 mg/kg) reduced burying behavior in Wistar animals. However, antalarmin (10 mg/kg) tended to increase rather than reducing this behavior when tested in the msP lines, an effect that appeared more marked in the GG as compared to the AA line. CONCLUSION: The present data suggest that rats with msP genetic background are more anxious and show different sensitivity to stress and CRF1-R blockade than Wistars. The point mutations occurring in the CRF1-R gene do not seem to influence basal anxiety while they appear to affect active responses to stress.

Binge-like consumption of caloric and non-caloric palatable substances in ad libitum-fed C57BL/6J mice: pharmacological and molecular evidence of orexin involvement.

The orexin (OX) system has been implicated in food-reinforced behavior, food-seeking and food overconsumption. Recent evidence suggests that OX signaling might influence consumption of palatable foods with high reinforcing value depending upon the caloric status of the animal. The present study evaluates from a pharmacological and a molecular approach the contribution of OX to excessive binge-like consumption of highly preferred palatable substances (sucrose and saccharin) in ad libitum-fed C57BL/6J mice. The main findings of this study are: (1) intraperitoneal (ip) injection of SB-334867 (10, 20 or 30mg/kg), a selective OXR1 antagonist, significantly decreased binge-like consumption of sucrose (10%, w/v) and saccharin (0.15%, w/v) during the test day in a Drinking in the Dark procedure in ad libitum-fed animals, without evidence of any significant alteration of locomotor activity. (2) Four repetitive, 2-h daily episodes of sucrose and saccharin (but not water) binge-like drinking significantly dampened OX mRNA expression in the LH. Present findings show for the first time a role for OXR1 signaling in binge-like consumption of palatable substances in animals under no caloric needs. Targeting OXR1 could represent a novel pharmacological approach to treat binge-eating episodes.

Repeated binge-like ethanol administration during adolescence cause decreased C-Fos immunoreactivity in amygdala and arcuate nucleus in adult Sprague-Dawley rats / La administración repetida de etanol, tipo atracón, durante la adolescencia provoca descenso en la expresión de C-Fos en la amígdala y núcleo arqueado de ratas Sprague-Dawley adultas

Binge alcohol drinking during adolescence has been associated with neurotoxicity and increased risk for the development of alcohol use disorders. There is evidence that acute and chronic ethanol administration alters c-fos expression, an indirect index of cellular activity, in different brain regions in adult rats. We evaluate here if a binge-like pattern of ethanol exposure during adolescence has a relevant impact on basal and/or ethanol-stimulated regional c-fos activity during adulthood. For that aim, Sprague-Dawley rats PND 25 were saline pre-treated, (SP group) or binge-ethanol pre-treated (BEP group) for two­consecutive days, at 48-h intervals, over a 14-day period (PND 25 to PND 38). At adult stage (PND 63) and following 25 ethanol-free days, we evaluated c-fos immunoreactivity in response to saline or acute ethanol (1.5 or 3.0 g/kg) in the hypothalamus and amygdala. We found that acute ethanol administration dose-dependently increased c-fos activity in the the Paraventricular nucleus of the hypothalamus (PVN). Interestingly, binge-ethanol exposure during adolescence significantly reduced basal c-fos activity during adulthood in the Central nucleus of the amygdala (CeA) and the Arcuate nucleus of hypothalamus (Arc). We conclude that binge-like ethanol administration during adolescence causes long-term disturbances in basal neural activity in brain areas critically involved with ethanol consumption.

El consumo en atracón durante la adolescencia está asociado con neurotoxicidad y con el riesgo de desarrollar un trastorno en el uso de alcohol. Diversos estudios muestran que la administración aguda y crónica de alcohol en ratas adultas altera la expresión de c-fos, un marcador indirecto de actividad celular, en diferentes áreas cerebrales. Nosotros evaluamos si el patrón de consumo de alcohol en atracón durante la adolescencia tiene un impacto en la actividad basal de c-fos en esas regiones activadas por el alcohol. Utilizamos ratas Sprague-Dawley en su día post-natal 25 (PND25) tratadas con suero salino (grupo SP) o con etanol tipo atracón (grupo BEP) durante dos días consecutivos, en intervalos de 48 h, durante 14 días (PND25- PND38). En la edad adulta (PND63) y después de 25 días sin etanol, evaluamos la inmunorreactividad para c-fos en respuesta a una administración aguda de suero salino o etanol (1,5 ó 3,0 g/kg) en diferentes regiones cerebrales. La administración de alcohol incrementó de manera dosis-dependiente la actividad de c-fos en el núcleo paraventricular del hipotálamo. Además la exposición a etanol tipo atracón durante la adolescencia disminuyó la actividad basal de c-fos en la adultez en el núcleo central de la amígdala y en el núcleo arqueado del hipotálamo. Concluimos que el consumo de alcohol en atracón durante la adolescencia causa problemas a largo plazo en la actividad basal de regiones cerebrales implicadas en el consumo de alcohol.

Effects of a single high dose of Chlorpyrifos in long-term feeding, ethanol consumption and ethanol preference in male Wistar rats with a previous history of continued ethanol drinking.

Chlorpyrifos (CPF) is an organophosphate compound that is slowly delivered in the organism after subcutaneous injection, keeping acetylcholinesterase (AChE) activity mildly inhibited for weeks. We have previously reported reduced voluntary ethanol drinking 8 weeks post-CPF administration in Wistar rats when AChE activity was almost completely recovered. Additionally, the OPs disrupt the functioning of certain neurochemical systems and modify the formation and/or degradation of some neuropeptides with a known role in regulating voluntary consumption of alcohol. Moreover, chronic ethanol intake significantly alters the regional expression of some of these neurochemical systems. Thus, the present study explored whether a previous history with ethanol consumption modify the disturbance in the voluntary ethanol consumption induced by CPF administration. For this aim, we measured ethanol consumption in increasing concentrations (8%, 15% and 20% w/v) from 4 days to 8 weeks following a single dose of CPF. Two experiments were carried out; experiment 1 was conducted in ethanol-naïve rats and experiment 2, in animals with a previous history of ethanol drinking before CPF administration. Additionally, food and body weight measures were collected. We report here a significant increase in ethanol consumption and preference at high ethanol concentrations (15% and 20%) in CPF-treated animals with a previous history of ethanol consumption (experiment 1) and a long-lasting increase in food intake both in ethanol-exposed (experiment 1) and ethanol-naïve CPF-treated rats (experiment 2). Present data are discussed under the interesting idea that CPF targets neurobiological pathways critically involved with ethanol consumption. Additionally, we conclude that CPF effects on voluntary ethanol consumption are ethanol-experience dependent.