Behavioral and inflammatory changes in rats induced by a three-hit stress model: Implications for psychiatric disorders.

Many aspects of the impact of childhood trauma remain unknown, such as the age at which individuals are most vulnerable to trauma, whether traumatic experiences have more severe and lasting effects when experienced early in life, and whether early life trauma causes psychiatric conditions such as anxiety and major depressive disorder (MDD) that persist over time or evolve into other disorders. Thus, this study aimed to investigate the impact of traumatic experiences in childhood on susceptibility to mood disorders in adulthood, particularly MDD. Animal models were used to address these questions, and different stressor protocols at various stages of the offspring's life were used. Three-hit starting with injections of Poly: IC was performed on the 9th day of gestation and then considered the first stressor. After birth, the animals were exposed to the maternal deprivation (MD) protocol, which separated the pups from the mother 3 h a day during the first ten days of life. From the 60th day of life, the animals were divided to receive the chronic mild stress (CMS) protocol over 21 days. The stressors can induce anxiety-like behaviors, such as increased locomotor activity through a maternal immune activation protocol using Poly: IC and demonstrating depressive-like behaviors through the MD and CMS protocols. It also showed changes in brain structures for pro-inflammatory parameters, IL-1ß and TNF-α, and alterations in anti-inflammatory parameters, IL-4 and IL-10, at different ages of life. The study also found that regulating pro- and anti-inflammatory cytokines is necessary for appropriate neuronal behavior, and stress responses can be both friendly and enemy, with costs and benefits balanced to provide the best-fit result. In conclusion, phenotypic characteristics of animals' life history are shaped by signals transmitted directly or indirectly to developing animals, known as "predictive adaptive responses."

Ômega 3 na gestação e os impactos na depressão pós-parto: uma revisão narrativa / Omega 3 during pregnancy and impacts on postpartum depression: a narrative review / Omega 3 durante el embarazo e impactos en la depresión postparto: una revisión narrativa

Objetivo: Evidenciar através de uma revisão integrativa os resultados clínicos atuais do impacto do consumo de ômega 3 frente a depressão pós-parto. Método: Revisão integrativa da literatura realizada no período de Fevereiro a Julho de 2023 nas bases de dados Pubmed, LILACS, Medline e Scielo. Resultados:Foi realizada uma busca pelos descritores em saúde determinados e foram selecionadas 5 produções científicas que atenderam os critérios de inclusão. De modo geral, os trabalhos mostraram relações com a saúde do bebê e da mãe. No bebê, observou-se aumento do crescimento intrauterino, maior resposta do sistema nervoso central, melhor desenvolvimento neural, de retina, imunológico, cognitivo e físico. Já na saúde materna, observou-se aumento no processo antiinflamatório, melhor resposta imune, melhora no efeito neurotrófico do cérebro, aumento do metabolismo, melhora hormonal, menor risco cardiovascular, menores distúrbios neurológicos (incluindo a depressão) e distúrbios visuais. Conclusão:Mais estudos são necessários para elucidar os benefícios da suplementação de ômega-3 em gestantes no pós-parto

Objective: To show, through an integrative review, the current clinical results of the impact of omega 3 consumption on postpartum depression. Method:Integrative literature review carried out from February to July 2023 in the Pubmed, LILACS, Medline and Scielo databases. Results:A search was performed for specific health descriptors and 5 scientific productions that met the inclusion criteria were selected. In general, the studies showed relationships with the health of the baby and the mother. In the baby, there was an increase in intrauterine growth, greater response of the central nervous system, better neural, retinal, immunological, cognitive and physical development. In maternal health, there was an increase in the anti-inflammatory process, better immune response, improvement in the neurotrophic effect of the brain, increased metabolism, hormonal improvement, lower cardiovascular risk, lesser neurological disorders (including depression) and visual disturbances. Conclusion:More studies are needed to elucidate the benefits of omega-3 supplementation in postpartum pregnant women.

Objetivo: Mostrar, a través de una revisión integradora, los resultados clínicos actuales del impacto del consumo de omega 3 en la depresión posparto. Método:Revisión integrativa de la literatura realizada de febrero a julio de 2023 en las bases de datos Pubmed, LILACS, Medline y Scielo. Resultados:Se realizó una búsqueda de determinados descriptores de salud y se seleccionaron 5producciones científicas que cumplían con los criterios de inclusión. En general, los estudios mostraron relaciones con la salud del bebé y de la madre. En el bebé hubo un aumento del crecimiento intrauterino, mayor respuesta del sistema nervioso central,mejor desarrollo neural, retiniano, inmunológico, cognitivo y físico. En salud materna, hubo aumento del proceso antiinflamatorio, mejor respuesta inmunológica, mejora del efecto neurotrófico del cerebro, aumento del metabolismo, mejora hormonal, menor riesgo cardiovascular, menos trastornos neurológicos (incluyendo depresión) y alteraciones visuales. Conclusión:Se necesitan más estudios para dilucidar los beneficios de la suplementación con omega-3 en mujeres embarazadas posparto

Avaliação de constipação intestinal em estudantes de nível superior em uma universidade do extremo sul catarinense / Evaluation of intestinal constipation in higher level students at a university in the extreme south of catarina / Evaluación del estreñimiento intestinal en estudiantes de nivel superior de una universidad del extremo sur de catarina

Objetivo: Avaliar a presença de CI em estudantes das fases iniciais e finais dos cursos de Medicina, Nutrição e Engenharia Civil de uma Universidade no Extremo Sul Catarinense -Criciúma, através da ingestão alimentar e hídrica, dos tipos de fezes, se fazem uso, ou não, de alternativas de evacuação, comparando os hábitos alimentares com influência na constipação nos estudantes das três diferentes áreas. Método:Tal estudo foi realizado através de um questionário adaptado com questões sobre os hábitos de vida do indivíduo, juntamente com os critérios de Roma III, Roma IV e Escala de Bristol. Resultados:Caracterizou-se por 158 estudantes, sendo 71,5% (n=113) representam o sexo feminino e apenas 28,5% (n=45), o sexo masculino. A ingestão de líquidos demonstrou-se ser baixa, sendo 33,5% (n=53) ingerem mais que 1600ml/dia. Através da Escala de Bristol, 15,8% (n=25) revelaram evacuar o Tipo 1 e 2, caracterizando CI. Sobre os laxantes, apenas 3,2% (n=5) confirmaram a utilização. Foi verificada CI em 18,6% (n=21) das mulheres e 8,9% (n=4) dos homens. Conclusão:a alimentação destacou ser pobre em fibras. É notório que os estudantes sofrem com sintomas de CI. Através do auxílio de um profissional de nutrição, é necessário que equilibrem sua alimentação com fibras, consumem mais água diariamente e, consequentemente, auxiliem no bom funcionamento intestinal e na melhora da qualidade de vida.

Objective: To evaluate the presence of IC in students in the initial and final stages of Medicine, Nutrition and Civil Engineering courses at a University in the extreme south of Santa Catarina -Criciúma, through food and water intake, types of feces, whether they use, or no, of evacuation alternatives, comparing eating habits with influence on constipation in students from three different areas. Method: This study was carried out through a questionnaire answered with questions about the individual's life habits, together with the criteria of Rome III, Rome IV and Bristol Scale. Results: Characterized by 158 students, 71.5% (n=113) female and only 28.5% (n=45) male. Liquid intake was low, with 33.5% (n=53) ingesting more than 1600ml/day. Through the Bristol Scale, 15.8% (n=25) revealed to evacuate Type 1 and 2, characterizing CI. Regarding laxatives, only 3.2% (n=5) confirmed their use. CI was found in 18.6% (n=21) of women and 8.9% (n=4) of men. Conclusion:the highlighted diet is low in fiber. It is notorious that students suffer from HF symptoms. Through the help of a nutrition professional, it is necessary that they balance their diet with fiber, consume more water daily and, consequently, help in the good intestinal functioning and in the improvement of the qualityof life.

Objetivo:Evaluar la presencia de CI en estudiantes de las etapas inicial y final de las carreras de Medicina, Nutrición e Ingeniería Civil de una Universidad del extremo sur de Santa Catarina -Criciúma, a través de la ingesta de alimentos y agua, tipos de heces, si utilizan , o no, de alternativas de evacuación, comparando los hábitos alimentarios con influencia sobre el estreñimiento en estudiantes de las tres diferentes áreas. Método:Este estudio se realizó mediante un cuestionario adaptado con preguntas sobre el estilo de vida del individuo, junto con los criterios de Roma III, Roma IV y la Escala de Bristol. Resultados:Se caracterizó por 158 estudiantes, 71,5% (n=113) mujeres y sólo 28,5% (n=45) hombres. La ingesta de líquidos resultó ser baja, con un 33,5% (n=53) ingiriendo más de 1.600 ml/día. A través de la Escala de Bristol, el 15,8% (n=25) reveló evacuar Tipo 1 y 2, caracterizando CI. Respecto a los laxantes, sólo el 3,2% (n=5)confirmó su uso. La CI se verificó en el 18,6% (n=21) de las mujeres y en el 8,9% (n=4) de los hombres. Conclusión:la dieta era baja en fibra. Es notorio que los estudiantes padecen síntomas de CI. Con la ayuda de un profesional de la nutrición, es necesario que equilibren su dieta con fibra, consuman más agua diariamente y, en consecuencia, ayuden en el buen funcionamiento intestinal y en la mejora de la calidad de vida.

Ansiedade e comportamento alimentar de estudantes de diferentes áreas de uma Universidade do sul catarinense / Anxiety and eating behavior of students from different areas of a University of southern catarinense / Ansiedad y comportamiento alimentario de estudiantes de diferentes áreas de un Universidad catarinense del sur

Objetivo: analisar a relação entre a ansiedade e a alimentação em estudantes de diversas áreas da graduação de uma Universidade do Sul Catarinense. Método: A pesquisa aconteceu durante o primeiro semestre de 2023. Para a obtenção de dados foi elaborado um questionário pelas pesquisadoras responsáveis via Google Forms ®. Foram realizadas perguntas sobre as condições socioeconômicas dos estudantes, estado de ansiedade, hábitos alimentares, dados como peso e altura e informações sobre o comportamento alimentar. Resultados: Observou-se uma amostra de 85 universitários das três áreas da graduação pesquisadas. Foi aplicado um questionário para verificar o estado nutricional dos estudantes, questões relacionadas com ansiedade, bem como alimentação, comportamento alimentar e comer compulsivamente. Identificou-se que 58,82% (n=50) do IMC dos universitários foi adequado/eutrófico, 78,82% (n=67) se sentiam ansiosos no dia a dia e 82,35% (n=70) relatam que a ansiedade tem relação com o comer compulsivo. Conclusão: Conclui-se que a ansiedade e o comer compulsivo são prejudiciais tanto para a saúde do estudante quanto para seu desempenho em seus estudos, bem como sua saúde física e mental.

Objective: to analyze the relationship between anxiety and eating in students from different areas of graduation at a University in Southern Santa Catarina. Method: The research took place during the first semester of 2023. To obtain data, a questionnaire was prepared by the responsible researchers via Google Forms ®. Questions were asked about the students' socioeconomic conditions, state of anxiety, eating habits, data such as weight and height, and information about eating behavior. Results: A sample of 85 university students from the three undergraduate areas surveyed was observed. A questionnaire was applied to verify the nutritional status of students, issues related to anxiety, as well as food, eating behavior and compulsive eating. It was identified that 58.82% (n=50) of the BMI of university students was adequate/eutrophic, 78.82% (n=67) felt anxious in their daily lives and 82.35% (n=70) reported that anxiety is related to compulsive eating. Conclusion: It is concluded that anxiety and compulsive eating are harmful both for the student's health and for their performance in their studies, as well as their physical and mental health.

Objetivo: analizar la relación entre la ansiedad y la alimentación en estudiantes de diferentes áreas de graduación de una Universidad del Sur de Santa Catarina. Método: La investigación se desarrolló durante el primer semestre de 2023. Para la obtención de datos se elaboró un cuestionario por parte de los investigadores responsables a través de Google Forms®. Se realizaron preguntas sobre las condiciones socioeconómicas de los estudiantes, estado de ansiedad, hábitos alimentarios, datos como peso y talla e información sobre la conducta alimentaria. Resultados: Se observó una muestra de 85 estudiantes universitarios de las tres carreras encuestadas. Se aplicó un cuestionario para verificar el estado nutricional de los estudiantes, temas relacionados con la ansiedad, así como la alimentación, conducta alimentaria y alimentación compulsiva. Se identificó que el 58,82% (n=50) del IMC de universitarios fue adecuado/eutrófico, el 78,82% (n=67) se sintió ansioso en su cotidiano y el 82,35% (n=70) refirió que la ansiedad está relacionada con la alimentación compulsiva. Conclusión: Se concluye que la ansiedad y la alimentación compulsiva son perjudiciales tanto para la salud del estudiante como para su desempeño en sus estudios, así como su salud física y mental

Folic Acid Supplementation in the Gestational Phase of Female Rats Improves Age-Related Memory Impairment and Neuroinflammation in Their Adult and Aged Offspring.

Folic acid (FA) supplementation is important during pregnancy to avoid malformations in the offspring. However, it is unknown if it can affect the offspring throughout their lives. To evaluate the offspring, female mother rats (dams) were separated into 5 groups: Four groups received the AIN-93 diet, divided into control and FA (5, 10, and 50 mg/kg), and an additional group received a FA-deficient diet, and the diet was performed during pregnancy and lactation. We evaluated the female offspring of these dams (at 2 and 18 months old). The aged offspring fed with FA-deficient diet presented habituation, spatial and aversive memory impairment and the FA maternal supplementation prevented this. The natural aging caused an increase in the TNF-α and IL-1ß levels in the hippocampus from 18-month-old offspring. FA maternal supplementation was able to prevent the increase of these cytokines. IL-4 levels decreased in the prefrontal cortex from aged control rats and FA prevented it. FA deficiency decreased the levels of IL-4 in the hippocampus of the young offspring. In addition, natural aging and FA deficiency decreased brain-derived neurotrophic factor levels in the hippocampus and nerve growth factor levels in the prefrontal cortex and FA supplementation prevented it. Thus, the present study shows for the first time the effect of FA maternal supplementation on memory, cytokines, and neurotrophins in the aged offspring.

Antioxidant Therapy Alters Brain MAPK-JNK and BDNF Signaling Path-ways in Experimental Diabetes Mellitus.

This study was designed to investigate the effects of treatment with the antioxidants N-acetylcysteine (NAC) and deferoxamine (DFX) in intracellular pathways in the brain of diabetic rats. To conduct this study we induced diabetes in Wistar rats with a single injection of alloxan, and afterwards rats were treated with NAC or DFX for 14 days. Following treatment completion, the immunocontent of c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase-38 (MAPK38), brain-derived neurotrophic factor (BDNF), and protein kinases A and C (PKA and PKC) were determined in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens (NAc). DFX treatment increased JNK content in the PFC and NAc of diabetic rats. In the amygdala, JNK was increased in diabetics treated with saline or NAC. MAPK38 was decreased in the PFC of control and in diabetic rats treated with NAC or DFX; and in the NAc in all groups. PKA was decreased in the PFC with DFX treatment. In the amygdala, PKA content was increased in diabetic rats treated with either saline or NAC, compared to controls; and it was decreased in either NAC or DFX-treated groups, compared to saline-treated diabetic animals. In the NAc, PKA was increased in NAC-treated diabetic rats. PKC was increased in the amygdala of NAC-treated diabetic rats. In the PFC, the BDNF levels were decreased following treatment with DFX in diabetic rats. In the hippocampus of diabetic rats the BDNF levels were decreased. However, treatment with DFX reversed this effect. In the amygdala the BDNF increased with DFX in non-diabetic rats. In the NAc DFX treatment increased the BDNF levels in diabetic rats. In conclusion, both diabetes and treatment with antioxidants were able to alter intracellular pathways involved in the regulation of cell survival in a brain area and treatment-dependent fashion.

The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease.

Aging is a normal physiological process accompanied by cognitive decline. This aging process has been the primary risk factor for development of aging-related diseases such as Alzheimer's disease (AD). Cognitive deficit is related to alterations of neurotrophic factors level such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF). These strong relationship between aging and AD is important to investigate the time which they overlap, as well as, the pathophysiological mechanism in each event. Considering that aging and AD are related to cognitive impairment, here we discuss the involving these neurotrophic factors in the aging process and AD.

Baseline acetylcholinesterase activity and serotonin plasma levels are not associated with delirium in critically ill patients.

OBJECTIVE: The aim of this study was to investigate whether plasma serotonin levels or acetylcholinesterase activities determined upon intensive care unit admission could predict the occurrence of acute brain dysfunction in intensive care unit patients. METHODS: A prospective cohort study was conducted with a sample of 77 non-consecutive patients observed between May 2009 and September 2010. Delirium was determined using the Confusion Assessment Method for the Intensive Care Unit tool, and the acetylcholinesterase and serotonin measurements were determined from blood samples collected up to a maximum of 24 h after the admission of the patient to the intensive care unit. RESULTS: In the present study, 38 (49.6%) patients developed delirium during their intensive care unit stays. Neither serum acetylcholinesterase activity nor serotonin level was independently associated with delirium. No significant correlations of acetylcholinesterase activity or serotonin level with delirium/coma-free days were observed, but in the patients who developed delirium, there was a strong negative correlation between the acetylcholinesterase level and the number of delirium/coma-free days, indicating that higher acetylcholinesterase levels are associated with fewer days alive without delirium or coma. No associations were found between the biomarkers and mortality. CONCLUSIONS: Neither serum acetylcholinesterase activity nor serotonin level was associated with delirium or acute brain dysfunction in critically ill patients. Sepsis did not modify these relationships.

Atividade basal de acetilcolinesterase e níveis plasmáticos de serotonina não se associam ao delirium em pacientes gravemente enfermos / Baseline acetylcholinesterase activity and serotonin plasma levels are not associated with delirium in critically ill patients

RESUMO Objetivo: Investigar se os níveis plasmáticos de serotonina e atividade de acetilcolinesterase determinados por ocasião da admissão à unidade de terapia intensiva preveem a ocorrência de disfunção cerebral aguda em pacientes internados em unidade de terapia intensiva. Métodos: Foi conduzido no período entre maio de 2009 e setembro de 2010 um estudo prospectivo de coorte em uma amostra com 77 pacientes não consecutivos. A ocorrência de delirium foi determinada utilizando a ferramenta Confusion Assessment Method for the Intensive Care Unit, tendo sido determinadas as avaliações de acetilcolinesterase e serotonina em amostras de sangue coletadas até um máximo de 24 horas após admissão do paciente à unidade de terapia intensiva. Resultados: No presente estudo, 38 pacientes (49,6%) desenvolveram delirium durante sua permanência na unidade de terapia intensiva. Nem os níveis de atividade de acetilcolinesterase nem os de serotonina tiveram associação independente com delirium. Não se observaram correlações significantes entre atividade de acetilcolinesterase e níveis de serotonina com o número de dias livres de delirium/coma, porém, em pacientes que desenvolveram delirium, ocorreu uma forte correlação negativa entre níveis de acetilcolinesterase e número de dias livres de delirium/coma, demonstrando que níveis mais elevados de acetilcolinesterase se associaram com menos dias de vida sem delirium e coma. Nenhuma associação foi identificada entre os biomarcadores e mortalidade. Conclusão: Nem a atividade de acetilcolinesterase nem os níveis séricos de serotonina se associaram com delirium ou disfunção cerebral aguda em pacientes gravemente enfermos. A ocorrência de sepse não modificou esse relacionamento. .

ABSTRACT Objective: The aim of this study was to investigate whether plasma serotonin levels or acetylcholinesterase activities determined upon intensive care unit admission could predict the occurrence of acute brain dysfunction in intensive care unit patients. Methods: A prospective cohort study was conducted with a sample of 77 non-consecutive patients observed between May 2009 and September 2010. Delirium was determined using the Confusion Assessment Method for the Intensive Care Unit tool, and the acetylcholinesterase and serotonin measurements were determined from blood samples collected up to a maximum of 24 h after the admission of the patient to the intensive care unit. Results: In the present study, 38 (49.6%) patients developed delirium during their intensive care unit stays. Neither serum acetylcholinesterase activity nor serotonin level was independently associated with delirium. No significant correlations of acetylcholinesterase activity or serotonin level with delirium/coma-free days were observed, but in the patients who developed delirium, there was a strong negative correlation between the acetylcholinesterase level and the number of delirium/coma-free days, indicating that higher acetylcholinesterase levels are associated with fewer days alive without delirium or coma. No associations were found between the biomarkers and mortality. Conclusions: Neither serum acetylcholinesterase activity nor serotonin level was associated with delirium or acute brain dysfunction in critically ill patients. Sepsis did not modify these relationships. .

Maternal deprivation disrupts mitochondrial energy homeostasis in the brain of rats subjected to ketamine-induced schizophrenia.

Maternal deprivation (MD) appears to be one of the environmental factors involved in the pathophysiology of schizophrenia. A widely used animal model of the schizophrenia involves the administration of ketamine, a dissociative anesthetic, NMDA receptors noncompetitive antagonist, that induce symptoms such as schizophrenia. To clarify the molecular mechanism of schizophrenia induced by MD, we investigated alterations in energetic metabolism, oxidative stress and neurotrophic factor levels in the brain of rats following MD and/or a single administration of ketamine during adulthood. Male Wistar rats were subjected to MD for 10 days. Additionally, these animals received acute ketamine (5, 15 or 25 mg/kg by intraperitoneal route, i.p.) during adulthood, and 30 min later, they were killed and the prefrontal cortex (PFC), the hippocampus and the striatum were removed for molecular analyses. Ketamine 25 mg/kg and/or MD and Ketamine 15 and 5 mg/kg with MD decreased the creatine kinase (CK) activity in the hippocampus. The enzyme activity of succinate dehydrogenase (SDH) in the Krebs cycle had increased in the striatum following the administration of ketamine 25 mg/kg, MD per se or MD plus ketamine 5 and 15 mg/kg. MD per se or MD combined with ketamine in different doses increased the activity of mitochondrial complexes. The PFC of animals subjected to MD and administered with ketamine 5 mg/kg exhibited increased protein carbonyl content. In the hippocampus, ketamine 15 mg/kg, ketamine 25 mg/kg and MD each increased the carbonyl content. In the striatum, the TBARS levels were increased by the administration of ketamine 25 mg/kg. Finally, in the hippocampus, MD alone or in combination with ketamine reduced the Nerve Growth Factor (NGF) levels; however, the Brain-derived Neurotrophic Factor (BDNF) levels were unaltered. In the present study, we suggest that MD increased the risk of psychotic symptoms in adulthood, altering different parameters of energy and oxidative stress. Our results suggest that adverse experiences occurring early in life may sensitize specific neurocircuits to subsequent stressors, inducing vulnerability, and may help us understand the pathophysiological mechanisms involved in this disorder.

Effects of acute administration of mazindol on brain energy metabolism in adult mice.

OBJECTIVES: Mazindol is a sympathomimetic amine, widely used as an anorectic agent in the treatment of obesity. This drug causes psychostimulant effects because of its pharmacological profile similar to amphetamine, acting like a monoamine reuptake inhibitor. However, the mechanisms underlying the action of mazindol are still not clearly understood. METHODS: Swiss mice received a single acute administration of mazindol (0.25, 1.25 and 2.5 mg/kg, ip) or saline. After 2 h, the animals were killed by decapitation; the brain was removed and used for the evaluation of activities of mitochondrial respiratory chain complexes, Krebs cycle enzymes and creatine kinase. RESULTS: Acute administration of mazindol decreased complex I activity only in the hippocampus. Complex IV activity was increased in the cerebellum (2.5 mg/kg) and cerebral cortex (0.25 mg/kg). Citrate synthase activity was increased in the cerebellum (1.25 mg/kg) and cerebral cortex (1.25 mg/kg), and creatine kinase activity was increased in the cerebellum (1.25 mg/kg). CONCLUSION: We suggest that the inhibition of complex I in the hippocampus only and activation of complex IV, citrate synthase and creatine kinase occurs because of a stimulus effect of mazindol in the central nervous system, which causes a direct impairment on energy metabolism.

Recent evidence and potential mechanisms underlying weight gain and insulin resistance due to atypical antipsychotics.

OBJECTIVE: Atypical antipsychotics (AAPs) promote obesity and insulin resistance. In this regard, the main objective of this study was to present potential mechanisms and evidence concerning side effects of atypical antipsychotics in humans and rodents. METHOD: A systematic review of the literature was performed using the MEDLINE database. We checked the references of selected articles, review articles, and books on the subject. RESULTS: This review provides consistent results concerning the side effects of olanzapine (OL) and clozapine (CLZ), whereas we found conflicting results related to other AAPs. Most studies involving humans describe the effects on body weight, adiposity, lipid profile, and blood glucose levels. However, it seems difficult to identify an animal model replicating the wide range of changes observed in humans. Animal lineage, route of administration, dose, and duration of treatment should be carefully chosen for the replication of the findings in humans. CONCLUSIONS: Patients undergoing treatment with AAPs are at higher risk of developing adverse metabolic changes. This increased risk must be taken into account when making decisions about treatment. The influence of AAPs on multiple systems is certainly the cause of such effects. Specifically, muscarinic and histaminergic pathways seem to play important roles.

Recent evidence and potential mechanisms underlying weight gain and insulin resistance due to atypical antipsychotics

Objective: Atypical antipsychotics (AAPs) promote obesity and insulin resistance. In this regard, the main objective of this study was to present potential mechanisms and evidence concerning side effects of atypical antipsychotics in humans and rodents. Method: A systematic review of the literature was performed using the MEDLINE database. We checked the references of selected articles, review articles, and books on the subject. Results: This review provides consistent results concerning the side effects of olanzapine (OL) and clozapine (CLZ), whereas we found conflicting results related to other AAPs. Most studies involving humans describe the effects on body weight, adiposity, lipid profile, and blood glucose levels. However, it seems difficult to identify an animal model replicating the wide range of changes observed in humans. Animal lineage, route of administration, dose, and duration of treatment should be carefully chosen for the replication of the findings in humans. Conclusions: Patients undergoing treatment with AAPs are at higher risk of developing adverse metabolic changes. This increased risk must be taken into account when making decisions about treatment. The influence of AAPs on multiple systems is certainly the cause of such effects. Specifically, muscarinic and histaminergic pathways seem to play important roles. .

Association between Na⁺,K⁺-ATPase activity and the vulnerability/resilience to mood disorders induced by early life experience.

There is increasing evidence that early life events can influence neurodevelopment and later susceptibility to disease. Chronic variable stress (CVS) has been used as a model of depression. The objective of this study was to evaluate the interaction between early experience and vulnerability to chronic variable stress in adulthood, analyzing emotional, metabolic and neurochemical aspects related to depression. Pups were (1) handled (10 min/day) or (2) left undisturbed from day 1 to 10 after birth. When the animals reached adulthood, the groups were subdivided and the rats were submitted or not to CVS, which consisted of daily exposure to different stressors for 40 days, followed by a period of behavioral tasks, biochemical (plasma corticosterone and insulin sensitivity) and neurochemical (Na⁺,K⁺-ATPase activity in hippocampus, amygdala and parietal cortex) measurements. Neonatally-handled rats demonstrated shorter immobility times in the forced swimming test, independently of the stress condition. There was no difference concerning basal corticosterone or insulin sensitivity between the groups. Na⁺,K⁺-ATPase activity was decreased in hippocampus and increased in the amygdala of neonatally-handled rats. CVS decreased the enzyme activity in the three structures, mainly in the non-handled group. These findings suggest that early handling increases the ability to cope with chronic variable stress in adulthood, with animals showing less susceptibility to neurochemical features associated with depression, confirming the relevance of the precocious environment to vulnerability to psychiatric conditions in adulthood.