Les rates amb més germans són menys ansioses quan són adultes

En aquest revelador estudi, científics de l'Institut de Neurociències de la UAB han investigat com influeix el nombre de germans d'una ventrada en el comportament dels animals quan són adults. Malgrat que, en les ventrades petites, cada criatura rep més atenció individual, les criades en "famílies" més grans són menys ansioses quan són adultes.En este revelador estudio, científicos del Instituto de Neurociencias de la UAB han investigado cómo influye el número de hermanos de una camada en el comportamiento de los animales cuando son adultos. A pesar de que, en las camadas pequeñas, cada cría recibe más atención individual, aquellas criadas en "familias" más grandes son menos ansiosas cuando son adultas.In this revealing study, scientists from the UAB Neurosciences Institute have investigated how the number of siblings in a litter can influence behaviour when the rats reach adulthood. Although, in smaller litters, every pup receives more individual attention, those raised in bigger "families" are less anxious in their adulthood

Modelos animales en psicopatología y psicofarmacología : del análisis experimental de la conducta a la neurogenética

En los primeros apartados del presente trabajo se consideran las diversas disciplinas que han motivado el desarrollo de los modelos animales, así como la aportación de éstos al progreso de las mismas. A continuación se exponen los criterios de validez predictiva, aparente, de constructo y convergente por los que se rige la validación de los modelos animales, al tiempo que se plantea la necesidad de considerar también un criterio de consistencia-fiabilidad en el uso e interpretación de los resultados experimentales, lo cual se ilustra con un ejemplo. Seguidamente, el contínuo progreso que experimentan los modelos animales en función del rápido avance científico en determinadas líneas de investigación se ilustra con la aparición y/o cambios de procedimiento de modelos de ansiedad, estrés o aprendizaje. Finalmente, se presenta una tabla resumen de los modelos animales más utilizados en el estudio de las principales psicopatologías y se comentan algunos modelos psicogenéticos, farmacogenéticos y neurogenéticosThe contributions of different scientific disciplines to the progress of the animal models, as well as the need of such models for the development of those areas, are considered in the first part of the present work. Criteria for validating animal models of human (normal and abnormal) behavior, such as predictive, face, construct and convergent validities, in addition to a new suggested criterion concerning the consistency/reliability in the use of the models and interpretation of the data, are discussed. In considering the progress of animal models, different examples regarding the development of certain analogues of anxiety, stress and learning are presented. Finally, the most used models for the main psychopatological categories are summarized in a table, and some psychogenetic, pharmacogenetic and neurogenetic models are commente

Analysis of Gender Differences in HRV of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Mobile-Health Technology

Síndrome de fatiga crònica; Diferències de gènere; Variabilitat de la freqüència cardíacaSíndrome de fatiga crónica; Diferencias de género; Variabilidad del ritmo cardíacoChronic fatigue syndrome; Gender differences; Heart rate variabilityIn a previous study using mobile-health technology (mHealth), we reported a robust association between chronic fatigue symptoms and heart rate variability (HRV) in female patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study explores HRV analysis as an objective, non-invasive and easy-to-apply marker of ME/CFS using mHealth technology, and evaluates differential gender effects on HRV and ME/CFS core symptoms. In our methodology, participants included 77 ME/CFS patients (32 men and 45 women) and 44 age-matched healthy controls (19 men and 25 women), all self-reporting subjective scores for fatigue, sleep quality, anxiety, and depression, and neurovegetative symptoms of autonomic dysfunction. The inter-beat cardiac intervals are continuously monitored/recorded over three 5-min periods, and HRV is analyzed using a custom-made application (iOS) on a mobile device connected via Bluetooth to a wearable cardiac chest band. Male ME/CFS patients show increased scores compared with control men in all symptoms and scores of fatigue, and autonomic dysfunction, as with women in the first study. No differences in any HRV parameter appear between male ME/CFS patients and controls, in contrast to our findings in women. However, we have found negative correlations of ME/CFS symptomatology with cardiac variability (SDNN, RMSSD, pNN50, LF) in men. We have also found a significant relationship between fatigue symptomatology and HRV parameters in ME/CFS patients, but not in healthy control men. Gender effects appear in HF, LF/HF, and HFnu HRV parameters. A MANOVA analysis shows differential gender effects depending on the experimental condition in autonomic dysfunction symptoms and HF and HFnu HRV parameters. A decreased HRV pattern in ME/CFS women compared to ME/CFS men may reflect a sex-related cardiac autonomic dysfunction in ME/CFS illness that could be used as a predictive marker of disease progression. In conclusion, we show that HRV analysis using mHealth technology is an objective, non-invasive tool that can be useful for clinical prediction of fatigue severity, especially in women with ME/CFS.This research was funded by “Ministerio de Ciencia e Innovación” of the Spanish Government, grant number PID2019-107473RB-C2

Treadmill exercise has minimal impact on obesogenic diet-related gut microbiome changes but alters adipose and hypothalamic gene expression in rats

Exercise has been extensively utilised as an effective therapy for overweight- and obesity-associated changes that are linked to health complications. Several preclinical rodent studies have shown that treadmill exercise alongside an unhealthy diet improves metabolic health and microbiome composition. Furthermore, chronic exercise has been shown to alter hypothalamic and adipose tissue gene expression in diet-induced obesity. However, limited work has investigated whether treadmill exercise commenced following exposure to an obesogenic diet is sufficient to alter microbiome composition and metabolic health. To address this gap in the literature, we fed rats a high-fat/high-sugar western-style cafeteria diet and assessed the effects of 4 weeks of treadmill exercise on adiposity, diet-induced gut dysbiosis, as well as hypothalamic and retroperitoneal white adipose tissue gene expression. Forty-eight male Sprague-Dawley rats were allocated to either regular chow or cafeteria diet and after 3 weeks half the rats on each diet were exposed to moderate treadmill exercise for 4 weeks while the remainder were exposed to a stationary treadmill. Microbial species diversity was uniquely reduced in exercising chow-fed rats, while microbiome composition was only changed by cafeteria diet. Despite limited effects of exercise on overall microbiome composition, exercise increased inferred microbial functions involved in metabolism, reduced fat mass, and altered adipose and hypothalamic gene expression. After controlling for diet and exercise, adipose Il6 expression and liver triglyceride concentrations were significantly associated with global microbiome composition. Moderate treadmill exercise induced subtle microbiome composition changes in chow-fed rats but did not overcome the microbiome changes induced by prolonged exposure to cafeteria diet. Predicted metabolic function of the gut microbiome was increased by exercise. The effects of exercise on the microbiome may be modulated by obesity severity. Future work should investigate whether exercise in combination with microbiome-modifying interventions can synergistically reduce diet- and obesity-associated comorbidities

Treadmill intervention attenuates the cafeteria diet-induced impairment of stress-coping strategies in young adult female rats

The current prevalence of diet-induced overweight and obesity in adolescents and adults is continuously growing. Although the detrimental biochemical and metabolic consequences of obesity are widely studied, its impact on stress-coping behavior and its interaction with specific exercise doses (in terms of intensity, duration and frequency) need further investigation. To this aim, we fed adolescent rats either an obesogenic diet (cafeteria diet, CAF) or standard chow (ST). Each group was subdivided into four subgroups according to the type of treadmill intervention as follows: a sedentary group receiving no manipulation; a control group exposed to a stationary treadmill; a low-intensity treadmill group trained at 12 m/min; and a higher intensity treadmill group trained at 17 m/min. Both the diet and treadmill interventions started at weaning and lasted for 8 weeks. Subjects were tested for anxiety-like behavior in the open field test and for coping strategies in the two-way active avoidance paradigm at week 7 and were sacrificed at week 8 for biometric and metabolic characterization. CAF feeding increased the weight gain, relative retroperitoneal white adipose tissue (RWAT %), and plasma levels of glucose, insulin, triglycerides and leptin and decreased the insulin sensitivity. Treadmill intervention partially reversed the RWAT% and triglyceride alterations; at higher intensity, it decreased the leptin levels of CAF-fed animals. CAF feeding decreased the motor activity and impaired the performance in a two-way active avoidance assessment. Treadmill intervention reduced defecation in the shuttle box, suggesting diminished anxiety. CAF feeding combined with treadmill training at 17 m/min increased the time spent in the center of the open field and more importantly, partially reversed the two-way active avoidance deficit. In conclusion, this study demonstrates that at doses that decreased anxiety-like behavior, treadmill exercise partially improved the coping strategy in terms of active avoidance behavior in the CAF-fed animals. This effect was not observed at lower doses of treadmill training

Slow and Fast Neocortical Oscillations in the Senescence-Accelerated Mouse Model SAMP8

The senescence-accelerated mouse prone 8 (SAMP8) model is characterized by accelerated, progressive cognitive decline as well as Alzheimer's disease (AD)-like neurodegenerative changes, and resembles the etiology of multicausal, sporadic late-onset/age-related AD in humans. Our aim was to find whether these AD-like pathological features, together with the cognitive deficits present in the SAMP8 strain, are accompanied by disturbances in cortical network activity with respect to control mice (SAM resistance 1, SAMR1) and, if so, how the alterations in cortical activity progress with age. For this purpose, we characterized the extracellular spontaneous oscillatory activity in different regions of the cerebral cortex of SAMP8 and SAMR1 mice under ketamine anesthesia at 5 and 7 months of age. Under these conditions, slow oscillations and fast rhythms generated in the cortical network were recorded and different parameters of these oscillations were quantified and compared between SAMP8 and their control, SAMR1 mice. The average frequency of slow oscillations in SAMP8 mice was decreased with respect to the control mice at both studied ages. An elongation of the silent periods or Down states was behind the decreased slow oscillatory frequency while the duration of active or Up states remained stable. SAMP8 mice also presented increased cycle variability and reduced high frequency components during Down states. During Up states, the power peak in the gamma range was displaced towards lower frequencies in all the cortical areas of SAMP8 with respect to control mice suggesting that the spectral profile of SAMP8 animals is shifted towards lower frequencies. This shift is reminiscent to one of the principal hallmarks of electroencephalography (EEG) abnormalities in patients with Alzheimer's disease, and adds evidence in support of the suitability of the SAMP8 mouse as a model of this disease. Although some of the differences between SAMP8 and control mice were emphasized with age, the evolution of the studied parameters as SAMR1 mice got older indicates that the SAMR1 phenotype tends to converge with that of SAMP8 animals. To our knowledge, this is the first systematic characterization of the cortical slow and fast rhythms in the SAMP8 strain and it provides useful insights about the cellular and synaptic mechanisms underlying the reported alterations

Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis

Heart rate variability (HRV) is an objective, non-invasive tool to assessing autonomic dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). People with CFS/ME tend to have lower HRV; however, in the literature there are only a few previous studies (most of them inconclusive) on their association with illness-related complaints. To address this issue, we assessed the value of different diurnal HRV parameters as potential biomarker in CFS/ME and also investigated the relationship between these HRV indices and self-reported symptoms in individuals with CFS/ME. In this case-control study, 45 female patients who met the 1994 CDC/Fukuda definition for CFS/ME and 25 age- and gender-matched healthy controls underwent HRV recording-resting state tests. The intervals between consecutive heartbeats (RR) were continuously recorded over three 5-min periods. Time- and frequency-domain analyses were applied to estimate HRV variables. Demographic and clinical features, and self-reported symptom measures were also recorded. CFS/ME patients showed significantly higher scores in all symptom questionnaires (p < 0.001), decreased RR intervals (p < 0.01), and decreased HRV time- and frequency-domain parameters (p < 0.005), except for the LF/HF ratio than in the healthy controls. Overall, the correlation analysis reached significant associations between the questionnaires scores and HRV time- and frequency-domain measurements (p < 0.05). Furthermore, separate linear regression analyses showed significant relationships between self-reported fatigue symptoms and mean RR (p = 0.005), RMSSD (p = 0.0268) and HFnu indices (p = 0.0067) in CFS/ME patients, but not in healthy controls. Our findings suggest that ANS dysfunction presenting as increased sympathetic hyperactivity may contribute to fatigue severity in individuals with ME/CFS. Further studies comparing short- and long-term HRV recording and self-reported outcome measures with previous studies in larger CFS/ME cohorts are urgently warranted

Effects of a Calorie-Restricted Cafeteria Diet and Oleuropein Supplementation on Adiposity and mRNA Expression of Energy Balance Related Genes in Obese Male Rats

Supplementation with natural bioactive compounds has been proposed to be a complementary tool to the calorie-restricted diets and physical exercise programs used to tackle human overweight, obesity and Metabolic syndrome. Herein, we evaluated the effects of 14 weeks of calorie-restricted cafeteria diet either alone or combined with oral administration of the polyphenol oleuropein in obese adult male rats, compared with a control group fed standard chow and a group fed cafeteria diet. Animals were sacrificed at the age of 26 weeks and several tissues of interest were removed. The results showed that both dietary interventions reduced the adiposity index (p < 0.05 and p < 0.01, respectively), and specifically the abdominal fat depots (mesenteric: p < 0.01 and p < 0.01, respectively; and epididymal: both diets p < 0.001) and restored the decreased soleus skeletal muscle mass. Both interventions decreased leptin mRNA expression in mesenteric white adipose tissue (p < 0.05) and normalized hypothalamic Agrp mRNA expression compared to cafeteria-fed obese rats (p < 0.05). However, only the calorie-restricted cafeteria diet supplemented with oleuropein induced additional lower retroperitoneal adipose accretion (p < 0.05) and increased hypothalamic leptin receptor mRNA levels (p < 0.05). Experiments with female animals, at different doses and longer intervention periods, are needed to better determine the potential benefits of this dietary treatment

Rcor2 underexpression in senescent mice: a target for inflammaging?

BACKGROUND: Aging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program. METHODS: To assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro. RESULTS: P8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes. CONCLUSIONS: Data presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammagin