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Roux-en-Y gastric bypass surgery (RYGB) remains an effective weight-loss method used to treat obesity. While it is successful in combating obesity, there are many lingering questions related to the changes in the brain following RYGB surgery, one of them being its effects on neuroinflammation. While it is known that chronic high-fat diet (HFD) contributes to obesity and neuroinflammation, it remains to be understood whether bariatric surgery can ameliorate diet-induced inflammatory responses. To examine this, rats were assigned to either a normal diet (ND) or a HFD for 8 weeks. Rats fed a HFD were split into the following groups: sham surgery with ad libitum access to HFD (sham-HF); sham surgery with calorie-restricted HFD (sham-FR); RYGB surgery with ad libitum access to HFD (RYGB). Following sham or RYGB surgeries, rats were maintained on their diets for 9 weeks before being euthanized. [3 H] PK11195 autoradiography was then performed on fresh-frozen brain tissue in order to measure activated microglia. Sham-FR rats showed increased [3 H] PK11195 binding in the amygdala (63%), perirhinal (60%), and ectorhinal cortex (53%) compared with the ND rats. Obese rats who had the RYGB surgery did not show this increased inflammatory effect. Since the sham-FR and RYGB rats were fed the same amount of HFD, the surgery itself seems responsible for this attenuation in [3 H] PK11195 binding. We speculate that calorie restriction following obese conditions may be seen as a stressor and contribute to inflammation in the brain. Further research is needed to verify this mechanism.
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Derivación Gástrica , Ratas , Animales , Derivación Gástrica/métodos , Restricción Calórica , Enfermedades Neuroinflamatorias , Obesidad/cirugíaRESUMEN
Alterations in dopamine neurotransmission are associated with obesity and food preferences. Otsuka Long-Evans Tokushima Fatty (OLETF) rats that lack functional cholecystokinin receptor type-1 (CCK-1R), due to a natural mutation, exhibit impaired satiation, are hyperphagic, and become obese. In addition, compared to lean control Long-Evans Tokushima (LETO) rats, OLETF rats have pronounced avidity for over-consuming palatable sweet solutions, have greater dopamine release to psychostimulants, reduced dopamine 2 receptor (D2R) binding, and exhibit increased sensitivity to sucrose reward. This supports altered dopamine function in this strain and its general preference for palatable solutions such as sucrose. In this study, we examined the relationship between OLETF's hyperphagic behavior and striatal dopamine signaling by investigating basal and amphetamine stimulated motor activity in prediabetic OLETF rats before and after access to sucrose solution (0.3 M) compared to non-mutant control LETO rats, as well as availability of dopamine transporter (DAT) using autoradiography. In the sucrose tests, one group of OLETF rats received ad libitum access to sucrose while the other group received an amount of sucrose equal to that consumed by the LETO. OLETFs with ad libitum access consumed significantly more sucrose than LETOs. Sucrose exerted a biphasic effect on basal activity in both strains, i.e., reduced activity for 1 week followed by increased activity in weeks 2 and 3. Basal locomotor activity was reduced (-17%) in OLETFs prior to sucrose, compared to LETOs. Withdrawal of sucrose resulted in increased locomotor activity in both strains. The magnitude of this effect was greater in OLETFs and the activity was increased in restricted compared to ad-libitum-access OLETFs. Sucrose access augmented AMPH-responses in both strains with a greater sensitization to AMPH during week 1, an effect that was a function of the amount of sucrose consumed. One week of sucrose withdrawal sensitized AMPH-induced ambulatory activity in both strains. In OLETF with restricted access to sucrose, withdrawal resulted in no further sensitization to AMPH. DAT availability in the nucleus accumbens shell was significantly reduced in OLETF compared with aged-matched LETO. Together, these findings show that OLETF rats have reduced basal DA transmission and a heightened response to natural and pharmacological stimulation.
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Dopamina , Receptores de Colecistoquinina , Animales , Ratas , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Obesidad/metabolismo , Ratas Endogámicas OLETF , Ratas Long-Evans , Receptores de Colecistoquinina/metabolismo , Sacarosa/farmacologíaRESUMEN
Diet-induced obesity is known to develop whether exposed to a high-energy diet (HED) or a high-fat diet (HFD). However, it is still not clear whether the elevated energy content or the macronutrient imbalance is the key factor in early disease progression. Therefore, this study compared the short-term effects of 2 widely used rodent obesogenic diets, an HFD with 60 kcal% fat content and a carbohydrate-based HED, on the body weight, body fat content, glucose tolerance, and neuronal taste responses in rats. We found that only HFD induced an early significant body weight increase compared with the control normal diet (ND) group, starting on week 4, and resulting in a significantly elevated body adiposity compared with both the ND and HED groups. Oral glucose tolerance test revealed no difference across groups. Subsequently, we also found that HFD resulted in a significant body weight gain even under energy-restricted (isocaloric to ND) conditions. In vivo electrophysiological recordings revealed that only the ad libitum HFD and not the isocaloric-HFD altered the brain stem gustatory neural responses to oral taste stimulation. In conclusion, this study showed that increased fat intake might result in significant body weight gain even under isocaloric and metabolically healthy conditions and demonstrated changes in central taste processing in an early stage of dietary obesity. A better understanding of these initial physiological changes may offer new drug targets for preventing obesity.
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Adiposidad , Dieta Alta en Grasa , Adiposidad/fisiología , Animales , Peso Corporal , Tronco Encefálico , Dieta Alta en Grasa/efectos adversos , Grasas de la Dieta/farmacología , Ingestión de Energía/fisiología , Obesidad/etiología , Ratas , GustoRESUMEN
Drug addiction is a chronic brain disease characterized by the uncontrolled use of a substance. Due to its relapsing nature, addiction is difficult to treat, as individuals can relapse following even long periods of abstinence and, it is during this time, that they are most vulnerable to overdose. In America, opioid overdose has been increasing for decades, making finding new treatments to help patients remain abstinent and prevent overdose deaths imperative. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have shown promise in reducing motivated behaviours for drugs of abuse. In this study, we test the effectiveness of the GLP-1 analogue, liraglutide (LIR), in reducing heroin addiction-like behaviour, and the potential side effects associated with the treatment. We show that daily treatment with LIR (0.1 mg/kg sc) increases the latency to take heroin, reduces heroin self-administration, prevents escalation of heroin self-administration and reduces drug-induced reinstatement of heroin-seeking behaviour in rats. A 1-h pretreatment time, however, was too short to reduce cue-induced seeking in our study. Moreover, we showed that, while LIR (0.1, 0.3, 0.6 and 1.0 mg/kg sc) supported conditioned taste avoidance of a LIR-paired saccharin cue, it did not elicit intake of the antiemetic kaolin in heroin-naïve or heroin-experienced rats. Further, 0.1 mg/kg LIR did not produce great disruptions in food intake or body weight. Overall, the data show that LIR is effective in reducing heroin taking and heroin seeking at doses that do not cause malaise and have a modest effect on food intake and body weight gain.
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Receptor del Péptido 1 Similar al Glucagón , Dependencia de Heroína , Liraglutida , Animales , Señales (Psicología) , Receptor del Péptido 1 Similar al Glucagón/agonistas , Heroína/farmacología , Dependencia de Heroína/tratamiento farmacológico , Liraglutida/farmacología , Ratas , AutoadministraciónRESUMEN
Parkinson's disease (PD), the second most common neurodegenerative disorder worldwide, is characterized by dopaminergic neuron degeneration and α-synuclein aggregation in the substantia nigra pars compacta of the midbrain. Emerging evidence has shown that dietary intake affects the microbial composition in the gut, which in turn contributes to, or protects against, the degeneration of dopaminergic neurons in affected regions of the brain. More specifically, the Mediterranean diet and Western diet, composed of varying amounts of proteins, carbohydrates, and fats, exert contrasting effects on PD pathophysiology via alterations in the gut microbiota and dopamine levels. Interestingly, the negative changes in the gut microbiota of patients with PD parallel changes that are seen in individuals that consume a Western diet, and are opposite to those that adhere to a Mediterranean diet. In this review, we first examine the role of prominent food groups on dopamine bioavailability, how they modulate the composition and function of the gut microbiota and the subsequent effects on PD and obesity pathophysiology. We then highlight evidence on how microbiota transplant and weight loss surgery can be used as therapeutic tools to restore dopaminergic deficits through optimizing gut microbial composition. In the process, we revisit dietary metabolites and their role in therapeutic approaches involving dopaminergic pathways. Overall, understanding the role of nutrition on dopamine bioavailability and gut microbiota in dopamine-related pathologies such as PD will help develop more precise therapeutic targets to rescue dopaminergic deficits in neurologic and metabolic disorders.
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Cirugía Bariátrica , Microbioma Gastrointestinal , Enfermedad de Parkinson , Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Microbioma Gastrointestinal/fisiología , Humanos , Obesidad/metabolismo , Enfermedad de Parkinson/metabolismoRESUMEN
AIMS: Currently, the only effective treatment for morbid obesity and its comorbidities is weight loss surgery (WLS). Growing evidence suggests that different types of WLS, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), have differential effects on alcohol consumption in humans and rats. Thus, we aimed to directly compare the effects of these two surgical procedures, for the first time in female rats, and to determine whether presence or absence of the ghrelin-producing stomach tissue has critical influence on postoperative alcohol intake. METHODS: We performed two experiments using an identical behavioral protocol, a continuous-access two-bottle choice protocol for various concentrations of ethanol (EtOH). In Experiment 1, 23 high fat diet (HFD) obese, female rats were randomized to three groups: RYGB, SG or sham-operated food-restricted (Sham) controls. In Experiment 2, HFD obese female rats received either sham (n = 11) or a modified RYGB surgery where the remnant stomach was removed (RYGB-X; n = 12). RESULTS: SG rats drank significantly less than RYGB for 4, 6 and 8% and significantly less than Sham for 6, 8 and 8% reinstatement. RYGB-X consumed significantly less EtOH than Sham across all concentrations, reaching significance for 6 and 8% reinstatement. CONCLUSION: These findings confirm reduced EtOH consumption by female SG rats as opposed to increased intake following RYGB, and provide the first experimental evidence that the remnant stomach in the RYGB procedure is contributory. Future studies in rats and humans are warranted to confirm that ghrelin plays a critical role in susceptibility to AUD development following WLS.
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Etanol/administración & dosificación , Derivación Gástrica/métodos , Animales , Femenino , Ghrelina/fisiología , Periodo Posoperatorio , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
AIMS: We aimed to investigate if differences in gut microbiota diversity and composition are associated with post-operative alcohol intake following bariatric surgery in a rat model. METHODS: Twenty-four female rats were randomized to three treatment groups: sham surgery, vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB). Stool was collected pre- and post-operatively and 16S rRNA gene amplification and sequencing was performed. Analysis focused on correlating microbial diversity, type of surgery and alcohol (EtOH) intake. RESULTS: Pre-operative stools samples on regular diet showed similar taxonomic composition and Shannon diversity among the three treatment groups. There was a significant decrease in Shannon diversity and a change in taxonomic composition of the gut microbiota after rats was fed high fat diet. Post-operatively, the RYGB group showed significantly lower taxonomic diversity than the VSG and sham groups, while the VSG and sham groups diversity were not significantly different. Taxonomic composition and function prediction based on PICRUSt analysis showed the RYGB group to be distinct from the VSG and sham groups. Shannon diversity was found to be negatively associated with EtOH intake. CONCLUSIONS: Changes in the taxonomic profile of the gut microbiota following bariatric surgery, particularly RYGB, are associated with increased EtOH intake and may contribute to increased alcohol use disorder risk through the gut-brain-microbiome axis.
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Cirugía Bariátrica , Etanol/administración & dosificación , Microbioma Gastrointestinal/fisiología , Animales , Femenino , Microbioma Gastrointestinal/genética , Modelos Animales , Datos de Secuencia Molecular , Distribución Aleatoria , RatasRESUMEN
No abstract avalilable.
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Trastorno Bipolar/psicología , Comprensión , Familia/psicología , Lenguaje , Imagen por Resonancia Magnética , Humanos , Proyectos PilotoRESUMEN
Roux-en-Y gastric bypass surgery (RYGB) is one of the most effective treatments for morbid obesity. However, increased substance abuse following RYGB has been observed clinically. This study examined the effects of RYGB on the dopamine system to elucidate these observed changes in reward-related behavior. Rats were assigned to four groups: normal diet with sham surgery, ad libitum high fat (HF) diet with sham surgery, restricted HF diet with sham surgery, and HF diet with RYGB surgery. Following surgeries, rats were kept on their respective diets for 9 weeks before they were sacrificed. [3 H]SCH 23390, [3 H]Spiperone, and [3 H]WIN35 428 autoradiography was performed to quantify the effects of diet and RYGB surgery on dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and dopamine transporter (DAT) binding. Rats on a chronic HF diet became obese with reduced D1R-like binding within the ventrolateral striatum and the nucleus accumbens core, reduced D2R-like binding in all areas of the striatum and nucleus accumbens core and shell, and reduced DAT binding in the dorsomedial striatum. Restricted HF diet rats showed similar reductions in D1R-like and D2-R-like binding as the obese rats, and reduced DAT binding within all areas of the striatum. Both RYGB and restricted HF diet rats showed similar weight reductions, with RYGB rats showing no difference in binding compared to controls. The observed changes in binding between non-treated obese rats and RYGB rats demonstrates that HF dietary effects on the dopamine system were reversed by RYGB.
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Obesity represents a major medical and public health problem worldwide. Efforts have been made to develop novel treatments, and among them bariatric surgery is used as an effective treatment to achieve significant, long-term weight loss and alleviate medical problems related to obesity. Alcohol use disorder (AUD) is also a leading cause of morbidity and mortality worldwide. Recent clinical studies have revealed a concern for bariatric surgery patients developing an increased risk for alcohol consumption, and for AUD. A better understanding of the relationship between bariatric surgery and potential later development of AUD is important, given the critical need of identifying patients at high risk for AUD. This paper reviews current clinical and basic science research and discusses potential underlying mechanisms. Special emphasis in this review is given to recent work suggesting that, alterations in alcohol metabolism/pharmacokinetics resulting from bariatric surgery are unlikely to be the primary or at least the only explanation for increased alcohol use and development of AUD, as changes in brain reward processing are also likely to play an important role. Additional studies are needed to clarify the potential role and mechanisms of how bariatric surgery may increase alcohol use and lead to AUD development.
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Consumo de Bebidas Alcohólicas/psicología , Alcoholismo/psicología , Cirugía Bariátrica/psicología , Encéfalo/fisiopatología , Obesidad/psicología , Complicaciones Posoperatorias/psicología , Consumo de Bebidas Alcohólicas/fisiopatología , Alcoholismo/complicaciones , Alcoholismo/fisiopatología , Humanos , Obesidad/complicaciones , Obesidad/cirugía , Complicaciones Posoperatorias/fisiopatologíaRESUMEN
BACKGROUND: Gastric bypass restricts food intake, with a limited component of malabsorption. Gut and brain hormone changes also facilitate improvements in weight and comorbidities. Patients' perception of taste and smell also change, along with reduced appetite for savory meals. Data on how changes in gastrointestinal physiology affect brain centers of perception and reward are sparse. METHODS: With IRB approval, we recruited 13 patients to undergo pre- and postoperative taste testing and functional MRI (fMRI) in response to sweet and salty solutions. A delivery system to the tongue was used, and patients rated intensity and pleasantness. They then underwent fMRI scanning. Sensory and reward areas of the brain were evaluated for activation. Subjects were then compared to non-obese non-surgical controls with the same taste paradigm and scanning twice, at 1 month apart. RESULTS: All subjects experienced significant weight loss at 1 month and at 1 year after surgery. As expected, after surgery brain activation in the reward center of the brain was significantly decreased in response to sweet solutions, but this effect was also seen in non-surgical controls, making this result inconclusive. In contrast, surgical patients had significantly increased activation in the reward center to salty taste compared both to their preoperative scans and to healthy controls. CONCLUSIONS: After GBS, brain activation in the reward system of obese patients responding to palatable tastes may be significantly changed, and such changes can be detected using fMRI. They do not always correlate with subjective reports of intensity and pleasantness. To verify that such taste-related activation changes are caused specifically by the GBS, taste function of a control group of obese patients should be studied during the same period of time without GBS intervention but with similar weight loss.
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Encéfalo/patología , Derivación Gástrica/efectos adversos , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/epidemiología , Trastornos del Gusto/epidemiología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Proyectos Piloto , Complicaciones Posoperatorias/etiología , Trastornos del Gusto/etiología , Trastornos del Gusto/patologíaRESUMEN
INTRODUCTION: Mentalization is the ability to attribute mental states (intentions, desires, thoughts, emotions) to others, and hence to predict their behaviour. This ability fundamentally determines our participation in social relationships and adaptation to society. A significant proportion of the disorders of the central nervous system (CNS) affects those brain structures and neurotransmitter systems that play a role in the mentalizing processes. Accordingly, a number of CNS disorders may be associated with mentalizing deficits, which may affect the outcome of these diseases. Here, we review recent research on mentalizing abilities in neurological diseases. METHODS: An internet database search was performed to identify publications on the subject. RESULTS: Sixty-two publications in English corresponded to the search criteria. These publications reported impaired mentalization in several neurological disorders (e.g. epilepsy, Parkinson's disease, multiple sclerosis, dementias, traumatic brain injury). DISCUSSION: The results indicate that a number of neurological disorders associate with mentalizing deficit. This deficit is often present in the early stages of the diseases and has a prognostic value, which in turn emphasizes the importance of the early detection and adequate rehabilitation.
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Trastornos del Conocimiento/diagnóstico , Cognición , Emociones , Relaciones Interpersonales , Enfermedades del Sistema Nervioso/psicología , Conducta Social , Teoría de la Mente , Adaptación Psicológica , Lesiones Encefálicas/psicología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Demencia/psicología , Diagnóstico Precoz , Epilepsia/psicología , Humanos , Esclerosis Múltiple/psicología , Enfermedades del Sistema Nervioso/rehabilitación , Pruebas Neuropsicológicas , Enfermedad de Parkinson/psicología , Valor Predictivo de las Pruebas , Pronóstico , Psicología del EsquizofrénicoRESUMEN
In this study we have examined a group of schizophrenia patients during the understanding of irony tasks, who had normal IQ. 14 patients and 14 healthy control subjects were included, 15 irony and 15 control tasks were invertigated during an fMRI investigation. During the contextual phase patients had shown a higher activitation in different brain regions. The healthy controls had shown deactivitation during this phase, while this couldn't be seen in the patiens group. During the irony phase healthy subjects activated brain regions known as mentalisation areas, while patients didn't. Our results can support the view, that behind schizophrenia patients mentalisation deficit the contextual phase can play the central role.
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Encéfalo/fisiopatología , Cognición , Comprensión , Imagen por Resonancia Magnética , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Ingenio y Humor como Asunto , Adulto , Encéfalo/patología , Estudios de Casos y Controles , Femenino , Actividad Nerviosa Superior , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Esquizofrenia/patologíaRESUMEN
The impairment of social functioning and difficulties in social integration are frequently found in patients with schizophrenia, and may affect the quality of life, thus revealing the underlying mechanisms of these differences appear to be of high importance. The impairment of social functioning has been reported in first-degree relatives of schizophrenia patients and individuals at ultra-high risk for psychosis. Two meta-analyses and 15 studies were reviewed, in which various ToM tests were performed involving first-degree relatives of patients with schizophrenia,with diverse findings, both positive and negative results have been found, and in addition other cognitive deficits were reported in some cases. In the background of different findings methodological differences can be presumed. Overall the social cognitive functions of first-degree relatives were found affected, which suggests the role of social cognition as endophenotypic marker of schizophrenia.
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Cognición , Endofenotipos , Familia/psicología , Esquizofrenia , Psicología del Esquizofrénico , Conducta Social , Percepción Social , Trastornos del Conocimiento/psicología , Humanos , Teoría de la MenteRESUMEN
Minor physical anomalies are mild, clinically and cosmetically insignificant errors of morphogenesis which have a prenatal origin and may bear major informational value for diagnostic, prognostic and epidemiological purposes. Since both the central nervous system and the skin are derived from the same ectodermal tissue in utero, minor physical anomalies can be external markers of abnormal brain development and they appear more commonly in neurodevelopmental disorders. Recently studies were published on the prevalence of minor physical anomalies in the relatives of patients with schizophrenia. In a systematic review of literature 11 studies were identified with mixed results. We suppose that the differentiation of minor malformations and phenogenetic variants can help to clarify the minor anomaly profile as a potential endophenotype in schizophrenia.
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Anomalías Múltiples/diagnóstico , Esquizofrenia , Anomalías Múltiples/genética , Familia , Humanos , Prevalencia , Esquizofrenia/diagnóstico , Esquizofrenia/genéticaRESUMEN
Obesity remains a significant global health challenge, with bariatric surgery remaining as one of the most effective treatments for severe obesity and its related comorbidities. This review highlights the multifaceted impact of bariatric surgery beyond mere physical restriction or nutrient malabsorption, underscoring the importance of the gut microbiome and neurohormonal signals in mediating the profound effects on weight loss and behavior modification. The various bariatric surgery procedures, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), act through distinct mechanisms to alter the gut microbiome, subsequently impacting metabolic health, energy balance, and food reward behaviors. Emerging evidence has shown that bariatric surgery induces profound changes in the composition of the gut microbiome, notably altering the Firmicutes/Bacteroidetes ratio and enhancing populations of beneficial bacteria such as Akkermansia. These microbiota shifts have far-reaching effects beyond gut health, influencing dopamine-mediated reward pathways in the brain and modulating the secretion and action of key gut hormones including ghrelin, leptin, GLP-1, PYY, and CCK. The resultant changes in dopamine signaling and hormone levels contribute to reduced hedonic eating, enhanced satiety, and improved metabolic outcomes. Further, post-bariatric surgical effects on satiation targets are in part mediated by metabolic byproducts of gut microbiota like short-chain fatty acids (SCFAs) and bile acids, which play a pivotal role in modulating metabolism and energy expenditure and reducing obesity-associated inflammation, as well as influencing food reward pathways, potentially contributing to the regulation of body weight and reduction in hedonic eating behaviors. Overall, a better understanding of these mechanisms opens the door to developing non-surgical interventions that replicate the beneficial effects of bariatric surgery on the gut microbiome, dopamine signaling, and gut hormone regulation, offering new avenues for obesity treatment.
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Cirugía Bariátrica , Hormonas Gastrointestinales , Microbioma Gastrointestinal , Obesidad Mórbida , Humanos , Dopamina , Encéfalo , Obesidad/cirugíaRESUMEN
Suicide is the most severe complication of major depressive disorder (MDD). Novel research assumes the role of immunological dysregulation in the background - several studies have reported alterations in the number of inflammatory cells related to both MDD and suicidality. There are currently no objective, routinely measured parameters to indicate suicidal vulnerability. However, altered inflammatory cell numbers and ratios have been proposed as potential biomarkers of suicide risk (SR). The present research aims to examine changes of these values related to increased SR in MDD as an assumed inflammatory state. We investigated laboratory parameters of psychiatric in-patients diagnosed with MDD (n = 101) retrospectively. Individuals with recent suicide attempt (SA) (n = 22) and with past SA (n = 19) represented the high SR group. MDD patients with no history of SA (n = 60) composed the intermediate SR group. We compared the number of neutrophil granulocytes, monocytes, lymphocytes, platelets, white blood cell count (WBC), neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red blood cell distribution width (RDW) and erythrocyte sedimentation rate (ESR). Furthermore, we evaluated alterations of these parameters related to antidepressant (AD) and antipsychotic (AP) treatment, which have been proved to have anti-inflammatory effects. We found a significant increase in neutrophil granulocyte count, NLR, monocyte count, MLR, WBC and ESR in patients with recent SA compared to patients with no history of SA. Moreover, there was a significant elevation in monocyte count, MLR, ESR and RDW in patients with high SR compared to patients with intermediate SR. AD treatment resulted in a significant decrease in neutrophil granulocyte count and NLR, however, it did not affect monocyte count and MLR. Assuming immunological mechanisms in the background of MDD and suicidality, our findings support the role of NLR as a biomarker of acute SR, though its alterations may be masked by possible anti-inflammatory effects of AD treatment in the long term. However, MLR, a marker exhibiting changes which are not attenuated by pharmacotherapy, may be a possible indicator of both acute and long-term suicidal vulnerability.
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INTRODUCTION: Theory of mind (ToM) is a crucial skill in navigating and functioning in the social world. Significant ToM impairment was consistently found in bipolar disorder; it can be both a state and trait marker of the disorder. However, most of the ToM tests are not sensitive enough to detect subtle individual differences, which would be necessary for an individualized treatment plan. The Short Story Task (SST) is a new way to sensitively assess individual differences in ToM performance. The aim of the study was to test the feasibility of SST in patients with bipolar disorder. METHOD: 31 persons (11 male, 20 female) with bipolar I disorder and 31 healthy individuals (15 males and 16 females) as a control group were recruited. SST was used to evaluate ToM performance. The SST uses a Hemingway novel, in which the patient is presented with a realistic social situation, where the motivations of the characters and the underlying relationships of events are not explicitly described. RESULTS: In the explicit mental state reasoning questions the CG (M = 8.06) had significantly higher (p < 0.001) scores than the persons with bipolar I disorder (M = 5.03). There was no ceiling effect for explicit ToM scores in either group. Participants in CG (M = 8.03) also significantly outperformed (p = 0.006) the BG participants (M = 6.55) in the comprehension questions. The spontaneous mental state inference question was performed equally (M = 0.23) in both groups. Group assignment (t = -3.503, p < 0.001), comprehension score (t = 2.864, p = 0.006), and spontaneous mentalization (t = 2.846, p = 0.006) significantly predicted the explicit ToM performance. CONCLUSIONS: Overall, we found that the Short Story Task is a promising tool for measuring ToM in patients with bipolar disorder without ceiling effect. Primarily explicit ToM was found to be deficient, which corresponds well with the ToM literature in bipolar disorder. Contrary to our hypothesis we could not detect impairment in spontaneous ToM and found that patients living with bipolar disorder also showed deficits in comprehension. The lack of assessment of neurocognitive skills is a significant limitation of the current study.
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Trastorno Bipolar , Teoría de la Mente , Humanos , Masculino , Femenino , Trastorno Bipolar/diagnóstico , Comprensión , Pruebas de Inteligencia , Motivación , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Clinical and preclinical research indicates that gastric weight loss surgeries, such as Roux-en-Y gastric bypass surgery, can induce alcohol use disorder (AUD). While numerous mechanisms have been proposed for these effects, one relatively unexplored potential mechanism is physical damage to the gastric branch of the vagus nerve, which can occur during bypass surgery. Therefore, we hypothesized that direct damage to the gastric branch of the vagus nerve, without altering other aspects of gastric anatomy, could result in increased alcohol intake. METHODS: To test this hypothesis, we compared alcohol intake and preference in multiple models in male Sprague-Dawley rats that received selective gastric branch vagotomy (VX) with rats who underwent sham surgery. Because the vagus nerve regulates hypothalamic-pituitary-adrenal (HPA) axis function, and alterations to HPA function are critical to the escalation of non-dependent alcohol intake, we also tested the hypothesis that gastric VX increases HPA function. RESULTS: We found that VX increases alcohol intake and preference in the every-other-day, two-bottle choice test and increases preference for 1 g/kg alcohol in the conditioned place preference test. The effects were selective for alcohol, as sucrose intake and preference were not altered by VX. We also found that VX increases corticotropin releasing factor (CRF) mRNA in the paraventricular nucleus of the hypothalamus (PVN), increases putative PVN CRF neuronal action potential firing, and increases corticosterone levels. CONCLUSIONS: Overall, these findings suggest that the vagus nerve may play a critical role in regulating HPA axis function via modulation of PVN CRF mRNA expression and putative PVN CRF neuronal activity. Furthermore, disruptions to vagal regulation of HPA axis function may increase alcohol intake and preference.
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Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal neuronal health in the brain by reversing some effects of chronic high-fat diet as well as ageing. Vagovagal neurocircuits appear to remain open to modulation and adaptation throughout life, and understanding of these mechanisms may help in development of novel interventions to alleviate environmental (e.g. dietary) ailments and also alter neuronal ageing.