Self-determined, goal orientations and motivational climate in physical education.

The aim of this study was to analyze the degree of prediction to which the goal orientation adopted by the student and the motivational climate created by the teacher as perceived by students in physical education classes, have on the students' self-determined behaviors. The sample included 846 high school students from the Murcia region (Spain) aged 12-19 years old. The Spanish versions of the Perception of Success Questionnaire, the Perceived Motivational Climate in Sport Questionnaire-2 and the Motivational Climate Scale were the instruments used to collect data. A descriptive, correlated and stepwise multiple regression analysis was carried out following the Self Determination Index. Results show that the majority of students were task oriented, they perceive a task climate and were intrinsically motivated. Moreover, the relevance of the role of the teacher in physical education classes was demonstrated, as the main predictor variable of self-determined behavior in students was the motivational climate.

Effect of Aromatic Herbs and Spices Present in the Mediterranean Diet on the Glycemic Profile in Type 2 Diabetes Subjects: A Systematic Review and Meta-Analysis.

BACKGROUND: The Mediterranean Diet (MedDiet) is the dietary pattern par excellence for managing and preventing metabolic diseases, such as Type 2 Diabetes (T2DM). The MedDiet incorporates spices and aromatic herbs, which are abundant sources of bioactive compounds. The aim of this study was to analyze the effect of all aromatic herbs and spices included in the MedDiet, such as black cumin, clove, parsley, saffron, thyme, ginger, black pepper, rosemary, turmeric, basil, oregano, and cinnamon, on the glycemic profile in T2DM subjects. METHODS: PubMed, Web of Science, and Scopus databases were searched for interventional studies investigating the effect of these aromatic herbs and spices on the glycemic profile in T2DM subjects. RESULTS: This systematic review retrieved 6958 studies, of which 77 were included in the qualitative synthesis and 45 were included in the meta-analysis. Our results showed that cinnamon, turmeric, ginger, black cumin, and saffron significantly improved the fasting glucose levels in T2DM subjects. The most significant decreases in fasting glucose were achieved after supplementation with black cumin, followed by cinnamon and ginger, which achieved a decrease of between 27 and 17 mg/dL. CONCLUSIONS: Only ginger and black cumin reported a significant improvement in glycated hemoglobin, and only cinnamon and ginger showed a significant decrease in insulin.

Oscillometric devices vs. arterial Doppler in measuring the ankle-arm index for the diagnosis of peripheral arterial disease. / Dispositivos oscilométricos frente a Doppler arterial en la medida del índice tobillo-brazo para el diagnóstico de la enfermedad arterial periférica.

INTRODUCTION: Peripheral arterial disease is a marker of vascular damage that is diagnosed by measuring the ankle-brachial index. The aim of this study was to determine the validity and agreement of the MESI ABPI-MD and Microlife WatchBP® office-ABI oscillometric devices with respect to the gold standard arterial Doppler. MATERIALS AND METHODS: Observational, cross-sectional, descriptive study of inpatients who underwent ABI measurement with the three devices. Values are considered normal between 1-1.4, indeterminate between 0.91-0.99 and pathological ≤0.9 and >1.4. RESULTS: A total of 187 patients (54.4% male) with a mean age of 66 years were included. The Doppler results were inferior to those of the oscillometric devices (median [IQR] 1.1 [0.2] vs. 1.2 [0.2], P<.05), with no significant differences between the automated devices (P=.29 for the right lower limb and P=.342 for the left lower limb). Both devices had high specificity (96.5-99.2%) and low sensitivity (29.5-45.4%). The correlation of the results was good-moderate for MESI and moderate for Microlife. The agreement between the two was acceptable-moderate. CONCLUSION: Automated oscillometric devices could be useful in asymptomatic patients as an alternative to arterial Doppler.

OptiMo-LDLr: An Integrated In Silico Model with Enhanced Predictive Power for LDL Receptor Variants, Unraveling Hot Spot Pathogenic Residues.

Familial hypercholesterolemia (FH) is an inherited metabolic disease affecting cholesterol metabolism, with 90% of cases caused by mutations in the LDL receptor gene (LDLR), primarily missense mutations. This study aims to integrate six commonly used predictive software to create a new model for predicting LDLR mutation pathogenicity and mapping hot spot residues. Six predictive-software are selected: Polyphen-2, SIFT, MutationTaster, REVEL, VARITY, and MLb-LDLr. Software accuracy is tested with the characterized variants annotated in ClinVar and, by bioinformatic and machine learning techniques all models are integrated into a more accurate one. The resulting optimized model presents a specificity of 96.71% and a sensitivity of 98.36%. Hot spot residues with high potential of pathogenicity appear across all domains except for the signal peptide and the O-linked domain. In addition, translating this information into 3D structure of the LDLr highlights potentially pathogenic clusters within the different domains, which may be related to specific biological function. The results of this work provide a powerful tool to classify LDLR pathogenic variants. Moreover, an open-access guide user interface (OptiMo-LDLr) is provided to the scientific community. This study shows that combination of several predictive software results in a more accurate prediction to help clinicians in FH diagnosis.

The impact of the COVID-19 pandemic in diabetes and dyslipidemia management in a Spanish region: a retrospective study of the Aragon population.

Introduction: Previous research has indicated that the COVID-19 outbreak had a negative impact on the diagnosis and management of cardiometabolic diseases. Our aim was to analyze the impact of the COVID-19 pandemic on the management of dyslipidemia and type 2 diabetes (T2D) in the Aragon region of Spain. Methods: We conducted an observational retrospective study, which included data from all patients diagnosed with active T2D or dyslipidemia in Aragon during 2019-2021. Data was collected from the BIGAN platform, a big database that includes all healthcare data from the Aragon population. Clinical, biochemical, and pharmacological prescription information was obtained for each patient and for each year. Results: Out of the total population of 1,330,000 in the Aragon region, 90,000 subjects were diagnosed with T2D each year, resulting in a prevalence of approximately 7%. The COVID-19 pandemic resulted in a decrease in the prevalence of this disease and a lower incidence during the year 2020. In addition, patients with T2D experienced a deterioration of their glucose profile, which led to an increase in the number of patients requiring pharmacological therapy. The prevalence of dyslipidemia was approximately 23.5% in both 2019 and 2020 and increased to 24.5% in 2021. Despite the worsening of the anthropometric profile, the lipid profile improved significantly throughout 2020 and 2021 compared to 2019. Moreover, the number of active pharmacological prescriptions increased significantly in 2021. Discussion: Our findings suggest that the overload of the health system caused by the COVID-19 pandemic has resulted in an underdiagnosis of T2D. Moreover, patients with T2D experienced a worsening of their glycemic profile, an increase in their pharmacological requirements, and lower performance of their analytical determinations. Dyslipidemic subjects improved their lipid profile although the value of lipid profile determination decreased between 2020 and 2021.

Absence of the influence of the APOE gene on the incidence of type 2 diabetes mellitus in a cohort of workers: Effect of diet and shift work.

BACKGROUND: APOE gene encoded a multifunctional protein in lipid metabolism, also associated with inflammatory markers. Type 2 diabetes (T2D) is a complex metabolic disease related to increased blood glucose, triglycerides and VLDL and associated with different dyslipidaemias. The aim of this study was to analyze whether the APOE genotype could determining the risk of developing T2D in a large cohort of workers. MATERIAL AND METHODS: Data from the Aragon Workers Health Study (AWHS) (n=4895) were used to investigate the relationship between glycemic levels and APOE genotype. All patients in the AWHS cohort had their blood drawn after an overnight fast and laboratory tests were performed on the same day as the blood drawn. Dietary and physical assessment was assessed by face-to-face interview. APOE genotype was determined by the Sanger sequencing method. RESULTS: The relationship between APOE genotype and glycemic profile showed that glucose, Hb1Ac, insulin and HOMA levels did not seem to be associated with the APOE genotype (p=0.563, p=0.605, p=0.333 and p=0.276, respectively). In addition, the T2D prevalence did not show an association with the APOE genotype (p=0.354). Along the same lines, blood glucose levels and T2D prevalence did not show association with the APOE allele. Shift work had some effect on the glycaemic profile, showing that night shift workers have significantly lower levels of glucose, insulin and HOMA (p<0.001). However, the APOE genotype did not show difference in the concentration of glycaemic parameters adjusting by sex, age and BMI, work shift and dietary parameters. CONCLUSION: Glycemic profile and T2D prevalence did not show any significant association with the APOE genotype. Besides, individuals, who worked in non-rotating night shift showed significantly lower glycemic levels, while workers in the morning-afternoon-night shift showed significantly higher values.

Association of Cholesterol and Oxysterols in Adipose Tissue With Obesity and Metabolic Syndrome Traits.

OBJECTIVE: Adipose tissue stores a substantial amount of body cholesterol in humans. Obesity is associated with decreased concentrations of serum cholesterol. During weight gain, adipose tissue dysfunction might be one of the causes of metabolic syndrome. The aim of this study is to evaluate cholesterol storage and oxidized metabolites in adipose tissue and their relationship with metabolic clinical characteristics. METHODS: Concentrations of cholesterol and oxysterols (27-hydroxycholesterol and 24S-hydroxycholesterol) in subcutaneous and visceral adipose tissue were determined by high-performance liquid chromatography with tandem mass spectrometry in 19 adult women with body mass index between 23 and 40 kg/m2 from the FAT expandability (FATe) study. Tissue concentration values were correlated with biochemical and clinical characteristics using nonparametric statistics. RESULTS: Insulin correlated directly with 24S-hydroxycholesterol in both adipose tissues and with 27-hydroxycholesterol in visceral tissue. Leptin correlated directly with 24S-hydroxycholesterol in subcutaneous adipose tissue. Tissue cholesterol correlated directly with 27-hydroxycholesterol in both adipose tissues and with 24S-hydroxycholesterol in visceral tissue, where cholesterol correlation with 24S-hydroxycholesterol was higher than with 27-hydroxycholesterol. In addition, some tendencies were observed: serum high-density lipoprotein cholesterol tended to be inversely correlated with visceral adipose tissue cholesterol; high-sensitivity C-reactive protein tended to be correlated directly with subcutaneous adipose 24S-hydroxycholesterol and inversely with visceral 27-hydroxycholesterol. CONCLUSIONS: Adipose tissue oxysterols are associated with blood insulin and insulin resistance. Tissue cholesterol correlated more with 27-hydroxycholesterol in subcutaneous adipose tissue and with 24S-hydroxycholesterol in visceral adipose tissue. Levels of adipose 24S-hydroxycholesterol seem to be correlated with some metabolic syndrome symptoms and inflammation while adipose 27-hydroxycholesterol could represent some protection against them.

Effect of the Consumption of Alcohol-Free Beers with Different Carbohydrate Composition on Postprandial Metabolic Response.

BACKGROUND: We investigated the postprandial effects of an alcohol-free beer with modified carbohydrate (CH) composition compared to regular alcohol-free beer. METHODS: Two randomized crossover studies were conducted. In the first study, 10 healthy volunteers received 25 g of CH in four different periods, coming from regular alcohol-free beer (RB), alcohol-free beer enriched with isomaltulose and a resistant maltodextrin (IMB), alcohol-free beer enriched with resistant maltodextrin (MB), and a glucose-based beverage. In the second study, 20 healthy volunteers were provided with 50 g of CH from white bread (WB) plus water, or with 14.3 g of CH coming from RB, IMB, MB, and extra WB. Blood was sampled after ingestion every 15 min for 2 h. Glucose, insulin, incretin hormones, TG, and NEFAs were determined in all samples. RESULTS: The increase in glucose, insulin, and incretin hormones after the consumption of IMB and MB was significantly lower than after RB. The consumption of WB with IMB and MB showed significantly less increase in glucose levels than WB with water or WB with RB. CONCLUSIONS: The consumption of an alcohol-free beer with modified CH composition led to a better postprandial response compared to a conventional alcohol-free beer.

SR-B1, a Key Receptor Involved in the Progression of Cardiovascular Disease: A Perspective from Mice and Human Genetic Studies.

High plasma level of low-density lipoprotein (LDL) is the main driver of the initiation and progression of cardiovascular disease (CVD). Nevertheless, high-density lipoprotein (HDL) is considered an anti-atherogenic lipoprotein due to its role in reverse cholesterol transport and its ability to receive cholesterol that effluxes from macrophages in the artery wall. The scavenger receptor B class type 1 (SR-B1) was identified as the high-affinity HDL receptor, which facilitates the selective uptake of cholesterol ester (CE) into the liver via HDL and is also implicated in the plasma clearance of LDL, very low-density lipoprotein (VLDL) and lipoprotein(a) (Lp(a)). Thus, SR-B1 is a multifunctional receptor that plays a main role in the metabolism of different lipoproteins. The aim of this review is to highlight the association between SR-B1 and CVD risk through mice and human genetic studies.

Dysbetalipoproteinemia and other lipid abnormalities related to apo E. / Disbetalipoproteinemia y otras alteraciones relacionadas con la apolipoproteína E.

Dysbetalipoproteinaemia (or type III hyperlipoproteinaemia) is a severe mixed hyperlipidaemia resulting from the accumulation of remnant chylomicron and VLDL particles in plasma, also called ß-VLDL. It is caused by a defect in the recognition by hepatic LDL and lipoprotein receptor-related protein (LRP) of ß-VLDL. Mutations in the APOE gene, especially in subjects homozygous for the ɛ2/ɛ2 allele, are responsible for this lack of receptor recognition. Dysbetalipoproteinaemia represents 2-5% of the mixed dyslipidaemias seen in Lipid Units, is highly atherogenic and predisposes to diffuse atheromatosis, either coronary, peripheral vascular, or carotid, so early diagnosis and treatment is necessary. The presence of hypertriglyceridaemia, with non-HDL cholesterol/apolipoprotein B ratios>1.43 (in mg/dL) followed by APOE genotyping is the method of choice in the diagnosis of dysbetalipoproteinaemia. It is a dyslipidaemia that responds well to hygienic-dietary treatment, although the combination of statin and fenofibrate is often necessary to achieve optimal control.

Maternal separation increases alcohol-drinking behaviour and reduces endocannabinoid levels in the mouse striatum and prefrontal cortex.

Childhood adversity is associated with an increased risk of mood, anxiety and substance use disorders. Maternal separation is a reliable rodent model of early life adversity that leads to depression-like symptoms, which may increase the vulnerability to alcohol consumption during adolescence. However, the specific alterations in the pattern of alcohol consumption induced by maternal separation and the underlying molecular mechanisms are still unclear. The purpose of this study is to evaluate the long-term effects of maternal separation with early weaning (MSEW) on emotional and social behaviour, alcohol rewarding properties, and alcohol consumption, abstinence and relapse in adolescent male C57BL/6 mice. In addition, endocannabinoid and monoamine levels were analysed in discrete brain areas. Results showed that MSEW mice presented emotional alterations related to depressive-like behaviour and modified endocannabinoid levels in the striatum and the prefrontal cortex. MSEW mice also showed impairments in alcohol-induced conditioned place preference and higher alcohol intake in a model of binge drinking. Moreover, MSEW animals displayed a higher propensity to relapse in the two-bottle choice paradigm following a period of alcohol abstinence associated with reduced monoamine levels in the striatum. Such results indicate that exposure to early life stress increased the vulnerability to alcohol binge-drinking during adolescence, which may be partially explained by decreased sensitivity to alcohol rewarding properties and the ability to potentiate alcohol intake following a period of abstinence.

Cognitive impairments associated with alterations in synaptic proteins induced by the genetic loss of adenosine A2A receptors in mice.

The study of psychiatric disorders usually focuses on emotional symptoms assessment. However, cognitive deficiencies frequently constitute the core symptoms, are often poorly controlled and handicap individual's quality of life. Adenosine receptors, through the control of both dopamine and glutamate systems, have been implicated in the pathophysiology of several psychiatric disorders such as schizophrenia and attention deficit/hyperactivity disorder. Indeed, clinical data indicate that poorly responsive schizophrenia patients treated with adenosine adjuvants show improved treatment outcomes. The A2A adenosine receptor subtype (A2AR) is highly expressed in brain areas controlling cognition and motivational responses including the striatum, hippocampus and cerebral cortex. Accordingly, we study the role of A2AR in the regulation of cognitive processes based on a complete cognitive behavioural analysis coupled with the assessment of neurogenesis and sub-synaptic protein expression in adult and middle-aged A2AR constitutional knockout mice and wild-type littermates. Our results show overall cognitive impairments in A2AR knockout mice associated with a decrease in new-born hippocampal neuron proliferation and concomitant changes in synaptic protein expression, in both the prefrontal cortex and the hippocampus. These results suggest a deficient adenosine signalling in cognitive processes, thus providing new opportunities for the therapeutic management of cognitive deficits associated with psychiatric disorders.

Maternal alcohol binge drinking induces persistent neuroinflammation associated with myelin damage and behavioural dysfunctions in offspring mice.

Alcohol binge drinking is on the increase in the young adult population, and consumption during pregnancy can be deleterious for foetal development. Maternal alcohol consumption leads to a wide range of long-lasting morphological and behavioural deficiencies known as foetal alcohol spectrum disorders (FASD), associated with neurodevelopmental disabilities. We sought to test the effects of alcohol on neuroimmune system activation and its potential relation to alcohol-induced neurodevelopmental and persistent neurobehavioural effects in offspring after maternal alcohol binge drinking during the prenatal period or in combination with lactation. Pregnant C57BL/6 female mice underwent a procedure for alcohol binge drinking either during gestation or both the gestation and lactation periods. Adult male offspring were assessed for cognitive functions and motor coordination. Early alcohol exposure induced motor coordination impairments in the rotarod test. Object recognition memory was not affected by maternal alcohol binge drinking, but Y-maze performance was impaired in pre- and early postnatal alcohol-exposed mice. Behavioural effects were associated with an upregulation of pro-inflammatory signalling (Toll-like receptor 4, nuclear factor-kappa B p65, NOD-like receptor protein 3, caspase-1, and interleukin-1ß), gliosis, neuronal cell death and a reduction in several structural myelin proteins (myelin-associated glycoprotein, myelin basic protein, myelin proteolipid protein and myelin regulatory factor) in both the prefrontal cortex and hippocampus of adult mice exposed to alcohol. Altogether, our results reveal that maternal binge-like alcohol consumption induces neuroinflammation and myelin damage in the brains of offspring and that such effects may underlie the persistent cognitive and behavioural impairments observed in FASD.

Binge ethanol drinking during adolescence modifies cocaine responses in mice.

Binge ethanol drinking is an emerging pattern of excessive consumption among adolescents and young adults. Repeated ethanol intoxication has negative consequences during critical periods of brain development. Therefore, binge ethanol intake represents a vulnerability factor that promotes subsequent manifestations of neuropsychiatric disorders. In this study, we investigated the effects of oral binge ethanol intake during adolescence on the subsequent effects of cocaine in C57BL/6 mice. Firstly, we evaluated the oral ethanol intake of two binge ethanol procedures with different ethanol concentrations (20% v/v versus 30%, v/v). The highest ethanol intake was found in mice exposed to the lower ethanol concentration (20% v/v). In a second experiment, mice exposed to binge ethanol procedure were evaluated to study the effects of cocaine on locomotor activity, behavioural sensitization, and the reinforcing effects of cocaine in the self-administration paradigm. Mice exposed to ethanol binging showed discrete detrimental effects in responses to cocaine in the different experiments evaluated. Our findings revealed that the pattern of binge ethanol consumption in adolescent mice here evaluated produced a weak facilitation of cocaine responses. The present study highlights the importance of interventions to limit the deleterious effects of binge ethanol drinking during adolescence.

Study of nucleation status in the second cell cycle of human embryo and its impact on implantation rate.

OBJECTIVE: To study nucleation status in two- and four-cell embryos and its effect on reproductive outcomes. DESIGN: Retrospective cohort study. SETTING: University-affiliated private center. PATIENT(S): A total of 1,679 embryos from 940 oocyte donation cycles from May 2012 to May 2014. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation, morphokinetics, and nucleation status restoration. RESULT(S): Multinucleation was present in 42.53% of embryos with known implantation data at the two-cell stage; it was present in approximately 14% of them at the four-cell stage. In all, 73.4% of the embryos were multinucleated at two cells and restored their nucleation status when they cleaved into four cells. Embryos with blastomeres multinucleated (more than two nuclei) at the four-cell stage showed a lower implantation rate. The average length of S-phase in the first embryo cell cycle in the positive known implantation data (KID+) embryos was longer than in KID- (15.50 hours vs. 14.38 hours) and slightly shorter in the second embryo cell cycle (8.35 hours in KID+ vs. 8.60 hours in KID-). CONCLUSION(S): Multinucleation in two-cell-stage embryos is a frequent event, which is reversible in a high proportion of embryos, without impact on the implantation rate; and embryos with multinucleated blastomeres have a reduced outcome compared with those with binucleated blastomeres when multinucleation is present in four-cell-stage embryos.

Morphokinetic behavior of euploid and aneuploid embryos analyzed by time-lapse in embryoscope.

BACKGROUND: Embryonic aneuploidy may result in miscarriage, implantation failure, or birth defects. Thus, it is clinically necessary to avoid the selection of aneuploid embryos during in vitro fertilization treatment. AIM: The aim of this study was to identify the morphokinetic differences by analyzing the development of euploid and aneuploid embryos using a time-lapse technology. We also checked the accuracy of a previously described model for selection of euploid embryos based on morphokinetics in our study population. MATERIALS AND METHODS: It is a retrospective study of 29 cycles undergoing preimplantation genetic screening from October 2013 to April 2015 at our center. Of 253 embryos, 167 suitable for biopsy embryos were analyzed for their chromosomal status using array-comparative genome hybridization (CGH). The morphokinetic behavior of these embryos was further analyzed in embryoscope using time-lapse technology. RESULTS: Among the analyzed embryos, 41 had normal and 126 had abnormal chromosome content. No significant difference in morphokinetics was found between euploid and aneuploid embryos. The percentage of embryos with blastulation was similar in the euploid (65.85%, 27/41) and aneuploid (60.31%, 76/126) embryos (P = 0.76). Although hard to define, majority of the chromosomal defects might be due to meiotic errors. On applying embryo selection model from Basile et al., embryos falling within optimal ranges for time to division to 5 cells (t5), time period of the third cell cycle (CC3), and time from 2 cell division to 5 cell division (t5-t2) exhibited greater proportion of normal embryos than those falling outside the optimal ranges (28.6%, 25.9%, and 26.7% vs. 17.5%, 20.8%, and 14.3%). CONCLUSION: Keeping a track of time interval between two stages can help us recognize aneuploid embryos at an earlier stage and prevent their selection of transfer. However, it cannot be used as a substitute for array CGH to select euploid embryos for transfer.

Genetic blockade of adenosine A2A receptors induces cognitive impairments and anatomical changes related to psychotic symptoms in mice.

Schizophrenia is a chronic severe mental disorder with a presumed neurodevelopmental origin, and no effective treatment. Schizophrenia is a multifactorial disease with genetic, environmental and neurochemical etiology. The main theories on the pathophysiology of this disorder include alterations in dopaminergic and glutamatergic neurotransmission in limbic and cortical areas of the brain. Early hypotheses also suggested that nucleoside adenosine is a putative affected neurotransmitter system, and clinical evidence suggests that adenosine adjuvants improve treatment outcomes, especially in poorly responsive patients. Hence, it is important to elucidate the role of the neuromodulator adenosine in the pathophysiology of schizophrenia. A2A adenosine receptor (A2AR) subtypes are expressed in brain areas controlling motivational responses and cognition, including striatum, and in lower levels in hippocampus and cerebral cortex. The aim of this study was to characterize A2AR knockout (KO) mice with complete and specific inactivation of A2AR, as an animal model for schizophrenia. We performed behavioral, anatomical and neurochemical studies to assess psychotic-like symptoms in adult male and female KO and wild-type (WT) littermates. Our results show impairments in inhibitory responses and sensory gating in A2AR KO animals. Hyperlocomotion induced by d-amphetamine and MK-801 was reduced in KO animals when compared to WT littermates. Moreover, A2AR KO animals show motor disturbances, social and cognitive alterations. Finally, behavioral impairments were associated with enlargement of brain lateral ventricles and decreased BDNF levels in the hippocampus. These data highlight the role of adenosine in the pathophysiology of schizophrenia and provide new possibilities for the therapeutic management of schizophrenia.

Repeated Exposure to D-Amphetamine Decreases Global Protein Synthesis and Regulates the Translation of a Subset of mRNAs in the Striatum.

Repeated psychostimulant exposure induces persistent gene expression modifications that contribute to enduring changes in striatal GABAergic spiny projecting neurons (SPNs). However, it remains unclear whether changes in the control of mRNA translation are required for the establishment of these durable modifications. Here we report that repeated exposure to D-amphetamine decreases global striatal mRNA translation. This effect is paralleled by an enhanced phosphorylation of the translation factors, eIF2α and eEF2, and by the concomitant increased translation of a subset of mRNAs, among which the mRNA encoding for the activity regulated cytoskeleton-associated protein, also known as activity regulated gene 3.1 (Arc/Arg3.1). The enrichment of Arc/Arg3.1 mRNA in the polysomal fraction is accompanied by a robust increase of Arc/Arg3.1 protein levels within the striatum. Immunofluorescence analysis revealed that this increase occurred preferentially in D1R-expressing SPNs localized in striosome compartments. Our results suggest that the decreased global protein synthesis following repeated exposure to D-amphetamine favors the translation of a specific subset of mRNAs in the striatum.

Maternal separation induces neuroinflammation and long-lasting emotional alterations in mice.

Early life experiences play a key role in brain function and behaviour. Adverse events during childhood are therefore a risk factor for psychiatric disease during adulthood, such as mood disorders. Maternal separation is a validated mouse model for maternal neglect, producing negative early life experiences that result in subsequent emotional alteration. Mood disorders have been found to be associated with neurochemical changes and neurotransmitter deficits such as reduced availability of monoamines in discrete brain areas. Emotional alterations like depression result in reduced serotonin availability and enhanced kynurenine metabolism through the action of indoleamine 2, 3-dioxygenase in response to neuroinflammatory factors. This mechanism involves regulation of the neurotransmitter system by neuroinflammatory agents, linking mood regulation to neuroinmunological reactions. In this context, the aim of this study was to investigate the effects of maternal separation with early weaning on emotional behaviour in mice. We investigated neuroinflammatory responses and the state of the tryptophan-kynurenine metabolic pathway in discrete brain areas following maternal separation. We show that adverse events during early life increase risk of long-lasting emotional alterations during adolescence and adulthood. These emotional alterations are particularly severe in females. Behavioural impairments were associated with microglia activation and disturbed tryptophan-kynurenine metabolism in brain areas related to emotional control. This finding supports the preeminent role of neuroinflammation in emotional disorders.

Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice.

Adverse early-life conditions induce persistent disturbances that give rise to negative emotional states. Therefore, early life stress confers increased vulnerability to substance use disorders, mainly during adolescence as the brain is still developing. In this study, we investigated the consequences of maternal separation, a model of maternal neglect, on the psychotropic effects of cocaine and the neuroplasticity of the dopaminergic system. Our results show that mice exposed to maternal separation displayed attenuated behavioural sensitization, while no changes were found in the rewarding effects of cocaine in the conditioned place preference paradigm and in the reinforcing effects of cocaine in the self-administration paradigm. The evaluation of neuroplasticity in the striatal dopaminergic pathways revealed that mice exposed to maternal separation exhibited decreased protein expression levels of D2 receptors and increased levels of the transcriptional factor Nurr1. Furthermore, animals exposed to maternal separation and treated with cocaine exhibited increased DA turnover and protein expression levels of DAT and D2R, while decreased Nurr1 and Pitx3 protein expression levels were observed when compared with saline-treated mice. Taken together, our data demonstrate that maternal separation caused an impairment of cocaine-induced behavioural sensitization possibly due to a dysfunction of the dopaminergic system, a dysfunction that has been proposed as a factor of vulnerability for developing substance use disorders.