Serotonergic mechanisms associated with experimental models of hypoxia: A systematic review.

PURPOSE: The aim of this systematic review was to explore and discuss the literature concerning the effects of hypoxia or anoxia during the perinatal period on the serotoninergic network in rodents, through mechanisms that lead to changes in serotonergic neurons, levels, segments of central nervous system affected, 5-HT transporter, and 5-HT receptor. METHODS: Literature searches were performed in Embase, Medline (PubMed), Web of Science, and SCOPUS, from April to July 2021, with a total of 1045 published studies found. Using a predefined protocol, as registered on the CAMARADES website, 10 articles were included in this review. The PRISMA statement was used for reporting this systematic review. The internal validity was assessed using the SYRCLE's risk of bias tool. RESULTS: Our main findings show that hypoxia in the first days of postnatal life led to a disturbance in the serotonergic system with reduced in 5-HT fibers, reduced brain levels of 5-HT and 5-HIAA, reduced SERT protein expression, and reduced receptor 5-HT7 . Putative mechanisms involving damage in the serotoninergic system include retrograde cell death resulting from primary damage mainly in forebrain areas, which impairs remote areas including serotonergic raphe nuclei. Other probable mechanisms associated with the serotoninergic network damage may be triggered by excitotoxic lesion and neuroinflammation. CONCLUSION: Hypoxia at the beginning of an animal's life leads to modification of the serotonergic components associated with putative mechanisms that include cell damage and neuroinflammation.

Influence of protein malnutrition on cutaneous wound healing in rats / Impacto da desnutrição proteica na cicatrização de feridas cutâneas em ratos

ABSTRACT Objective Investigate histological changes related to inflammatory response and collagen expression during wound healing in rats with protein malnutrition. Methods Twenty male Wistar rats underwent cutaneous surgery and were divided into two experimental groups: Malnourished (8% casein diet); Nourished (17% casein diet). Animals were euthanized after 5th and 10th days, descriptive and quantitative analyses were performed on sections stained with hematoxylin-eosin and sirius red, respectively. Statistical analysis of data using nonparametric Fisher's exact test with p<0.05 was carried out. Results At five days, increased fibroblast proliferation (p<0.01) and collagen expression (p<0.05) was observed in N5 group. After ten days, N10 and MN10 animals showed higher amount of granulation tissue and edema/inflammatory infiltrate independent of nutritional status (p>0.05), only N10 group showed fibroblast proliferation (p<0.01) and increased collagen expression (p<0.01). Conclusion Protein malnutrition seems not to influence inflammatory phase of healing, whereas it negatively effects fibroblast proliferation and collagen synthesis.

RESUMO Objetivo Investigar as alterações histológicas relacionadas à resposta inflamatória e à expressão de colágeno durante a cicatrização em ratos com desnutrição protéica. Métodos Vinte ratos Wistar machos foram submetidos à cirurgia cutânea e divididos em dois grupos experimentais: Desnutridos (dieta com caseína a 8%); Nutridos (17% de dieta com caseína). Animais foram eutanasiados após 5 e 10 dias, análises descritivas e quantitativas foram realizadas em cortes corados com hematoxilina-eosina e sirius vermelho, respectivamente. Análise estatística dos dados utilizando teste exato não paramétrico de Fisher com p<0,05 foi realizada. Resultados Aos cinco dias, observou-se aumento da proliferação fibroblástica (p<0,01) e expressão de colágeno (p<0,05) no grupo N5. Após 10 dias, animais N10 e MN10 apresentaram maior quantidade de tecido de granulação e edema/infiltrado inflamatório independente do estado nutricional (p>0,05), apenas grupo N10 apresentou proliferação fibroblástica (p<0,01) e aumento da expressão de colágeno (p<0,01). Conclusão A desnutrição protéica parece não influenciar na fase inflamatória da cicatrização, porém afeta negativamente a proliferação de fibroblastos e a síntese de colágeno.

L-tryptophan administration and increase in cerebral serotonin levels: Systematic review.

The amino acid tryptophan (2-Amino-3-(lH-indol-3-yl)-propanoic acid; Trp) is a precursor of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) that performs various brain functions. The administration of Trp is used in experimental studies to manipulate the serotonergic system, however the dose of Trp required to raise brain 5-HT levels is controversial. The aim of this study was to systemically review the effect of the administration of different doses of Trp on cerebral 5-HT levels. Two independent authors conducted a systematic review in the electronic databases. Twenty-five studies were included in the present review. Trp was administered orally, intraperitoneally or subcutaneous in adult animals. The brain 5-HT levels elevated after Trp administration in different intensities, dependent of the brain region evaluated and the time of administration. Further studies are needed to assess the dose-response of Trp administration to brain 5-HT levels.

Preoperative Nutritional Status and Clinical Complications in the Postoperative Period of Cardiac Surgeries.

Objective: This study aims to assess the preoperative nutritional status of patients and the role it plays in the occurrence of clinical complications in the postoperative period of major elective cardiac surgeries. Methods: Cross-sectional study comprising 72 patients aged 20 years or older, who underwent elective cardiac surgery. The preoperative nutritional assessment consisted of nutritional screening, anthropometry (including the measurement of the adductor pollicis muscle thickness) and biochemical tests. The patients were monitored for up to 10 days after the surgery in order to control the occurrence of postoperative complications. The R software, version 3.0.2, was used to statistically analyze the data. Results: Clinical complications were found in 62.5% (n=42) of the studied samples and complications of non-infectious nature were most often found. Serum albumin appeared to be associated with renal complications (P=0.026) in the nutritional status indicators analyzed herein. The adductor pollicis muscle thickness was associated with infectious complications and presented mean of 9.39±2.32 mm in the non-dominant hand (P=0.030). No significant correlation was found between the other indicators and the clinical complications. Conclusion: The adductor pollicis muscle thickness and the serum albumin seemed be associated with clinical complications in the postoperative period of cardiac surgeries.

Preoperative nutritional status and clinical complications in the postoperative period of cardiac surgeries

Abstract Objective: This study aims to assess the preoperative nutritional status of patients and the role it plays in the occurrence of clinical complications in the postoperative period of major elective cardiac surgeries. Methods: Cross-sectional study comprising 72 patients aged 20 years or older, who underwent elective cardiac surgery. The preoperative nutritional assessment consisted of nutritional screening, anthropometry (including the measurement of the adductor pollicis muscle thickness) and biochemical tests. The patients were monitored for up to 10 days after the surgery in order to control the occurrence of postoperative complications. The R software, version 3.0.2, was used to statistically analyze the data. Results: Clinical complications were found in 62.5% (n=42) of the studied samples and complications of non-infectious nature were most often found. Serum albumin appeared to be associated with renal complications (P=0.026) in the nutritional status indicators analyzed herein. The adductor pollicis muscle thickness was associated with infectious complications and presented mean of 9.39±2.32 mm in the non-dominant hand (P=0.030). No significant correlation was found between the other indicators and the clinical complications. Conclusion: The adductor pollicis muscle thickness and the serum albumin seemed be associated with clinical complications in the postoperative period of cardiac surgeries.

MATERNAL AND POST-WEANING EXPOSURE TO A HIGH FAT DIET PROMOTES VISCERAL OBESITY AND HEPATIC STEATOSIS IN ADULT RATS.

AIM: considering the frequent consumption of fat-rich diets by women of reproductive age, the aim of the present study was to investigate the effects of maternal consumption of a high-fat diet during the perinatal and/ or post-weaning period on the liver parameters and lipid metabolism of young rats. METHODS: Wistar female rats were fed a high-fat (H) or control (C) diet during pregnancy and lactation. The offspring were allocated to four groups: Control Control (CC, n = 11), offspring fed a control diet after weaning; Control High-fat (CH, n = 10), offspring fed a high-fat diet after weaning; High-fat High-fat (HH, n = 10), offspring of mothers H fed a high-fat diet after weaning; and High-fat Control (HC, n = 9), offspring of mothers H fed with control diet after weaning. RESULTS AND DISCUSSION: the food intake did not differ among the groups, however, the relative weight of the adipose tissue was higher in animals from the HC, HH and CH groups (p ≤ 0.005). Liver steatosis was found in the CH and HH animals, which also exhibited hypercholesterolemia (p ≤ 0.05). The levels of the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) were higher in the HH group, and the LDL level was higher in the CH group compared to the CC. The consumption of an obesogenic diet during critical periods of development may contribute to the occurrence of visceral obesity, liver steatosis and hypercholesterolemia in adult rats, even in the absence of changes in dietary intake.

Objetivo: teniendo en cuenta el consumo frecuente de dietas ricas en grasas por las mujeres en edad reproductiva, el objetivo del presente estudio fue investigar los efectos del consumo materno de una dieta alta en grasas durante el periodo perinatal y/o post-destete en el higado y el metabolismo de los lipidos en ratas jovenes. Métodos: ratas hembra Wistar fueron alimentadas durante el embarazo y la lactancia con un alto contenido de grasa (H) o de control (C). La descendencia se asigno a cuatro grupos: Control (CC, n = 11), descendencia alimentada con una dieta de control despues del destete; Control de dieta alta en grasa (CH, n = 10), crias alimentadas con una dieta alta en grasas despues del destete; Alta en grasas de alta en grasa (HH, n = 10), hijos de madres H alimentados con una dieta alta en grasas despues del destete; y Control de alta en grasa (HC, n = 9), hijos de madres H alimentados con dieta de control tras el destete. Resultados y discusión: la ingesta de alimentos no difirio entre los grupos; sin embargo, el peso relativo del tejido adiposo fue mayor en los animales de los grupos HC, HH y CH (p ≤ 0,005). La esteatosis hepatica se encontro en los CH y HH, que tambien presentaban hipercolesterolemia (p ≤ 0,05). Los niveles de las enzimas hepaticas alanina aminotransferasa (ALT) y gamma-glutamil transpeptidasa (GGT) fueron mayores en el grupo de HH, y el nivel de LDL fue mayor en el grupo CH en comparacion con el CC. El consumo de la dieta propicio la obesidad durante los periodos criticos del desarrollo y puede contribuir a la aparicion de obesidad visceral, esteatosis hepatica e hipercolesterolemia en ratas adultas, incluso en ausencia de cambios en la ingesta dietetica.

Maternal and post-weaning exposure to a high fat diet promotes visceral obesity and hepatic steatosis in adult rats / La exposición en el periodo perinatal y el postdestete a una dieta alta en grasas promueve la obesidad visceral y la esteatosis hepática en ratas adultas

Aim: considering the frequent consumption of fatrich diets by women of reproductive age, the aim of the present study was to investigate the effects of maternal consumption of a high-fat diet during the perinatal and/ or post-weaning period on the liver parameters and lipid metabolism of young rats. Methods: Wistar female rats were fed a high-fat (H) or control (C) diet during pregnancy and lactation. The offspring were allocated to four groups: Control Control (CC, n = 11), offspring fed a control diet after weaning; Control High-fat (CH, n = 10), offspring fed a high-fat diet after weaning; High-fat High-fat (HH, n = 10), offspring of mothers H fed a high-fat diet after weaning; and High-fat Control (HC, n = 9), offspring of mothers H fed with control diet after weaning. Results and discussion: the food intake did not differ among the groups, however, the relative weight of the adipose tissue was higher in animals from the HC, HH and CH groups (p ≤ 0.005). Liver steatosis was found in the CH and HH animals, which also exhibited hypercholesterolemia (p ≤ 0.05). The levels of the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) were higher in the HH group, and the LDL level was higher in the CH group compared to the CC. The consumption of an obesogenic diet during critical periods of development may contribute to the occurrence of visceral obesity, liver steatosis and hypercholesterolemia in adult rats, even in the absence of changes in dietary intake (AU)

Objetivo: teniendo en cuenta el consumo frecuente de dietas ricas en grasas por las mujeres en edad reproductiva, el objetivo del presente estudio fue investigar los efectos del consumo materno de una dieta alta en grasas durante el período perinatal y/o post-destete en el hígado y el metabolismo de los lípidos en ratas jóvenes. Métodos: ratas hembra Wistar fueron alimentadas durante el embarazo y la lactancia con un alto contenido de grasa (H) o de control (C). La descendencia se asignó a cuatro grupos: Control (CC, n = 11), descendencia alimentada con una dieta de control después del destete; Control de dieta alta en grasa (CH, n = 10), crías alimentadas con una dieta alta en grasas después del destete; Alta en grasas de alta en grasa (HH, n = 10), hijos de madres H alimentados con una dieta alta en grasas después del destete; y Control de alta en grasa (HC, n = 9), hijos de madres H alimentados con dieta de control tras el destete. Resultados y discusión: la ingesta de alimentos no difirió entre los grupos; sin embargo, el peso relativo del tejido adiposo fue mayor en los animales de los grupos HC, HH y CH (p ≤ 0,005). La esteatosis hepática se encontró en los CH y HH, que también presentaban hipercolesterolemia (p ≤ 0,05). Los niveles de las enzimas hepáticas alanina aminotransferasa (ALT) y gamma-glutamil transpeptidasa (GGT) fueron mayores en el grupo de HH, y el nivel de LDL fue mayor en el grupo CH en comparación con el CC. El consumo de la dieta propició la obesidad durante los períodos críticos del desarrollo y puede contribuir a la aparición de obesidad visceral, esteatosis hepática e hipercolesterolemia en ratas adultas, incluso en ausencia de cambios en la ingesta dietética (AU)

A perinatal palatable high-fat diet increases food intake and promotes hypercholesterolemia in adult rats.

The main goal of the present study was to evaluate the long-term effects of a perinatal palatable high-fat diet on the food intake and cholesterol profile of adult rats. Male Wistar rats (aged 22 days) were divided into two groups according to their mother's diet during gestation and lactation (C (p), n = 10; pups from control mothers; and HL(p) n = 10; pups from mothers fed a palatable high-fat diet). At the 76th day, pups were housed individually for 14 days, and daily food consumption was determined during a period of 6 days. Blood from 100-day-old rats was sampled by cardiac puncture. Fasting (12 h) serum glucose, total cholesterol, LDL-C, HDL-C, triglycerides (TG), and VLDL-C levels were determined. The measurement of food intake was higher in the animals submitted to a hyperlipidic diet during the perinatal period. Serum total cholesterol, LDL-C, HDL-C, TG, VLDL-C and glycemia were increased in the HL(p) group compared to the control group. Our findings show that an early life environment with a high-fat diet can contribute to metabolic disease in later life.

Efeito do tratamento com triptofano sobre parâmetros do comportamento alimentar em ratos adultos submetidos à desnutrição neonatal / Effects of tryptophan on the eating behavior of adult rats with neonatal malnutrition

OBJETIVO: Investigou-se os efeitos do tratamento com triptofano sobre o consumo alimentar em ratos adultos, submetidos ou não a desnutrição precoce. MÉTODOS: Sessenta e quatro ratos Wistar machos foram divididos em nutridos (n=32, caseína=17 por cento) e desnutridos (n=32, caseína=8 por cento), de acordo com a dieta materna empregada no período de lactação. Após o desmame, todos os ratos receberam dieta com 23 por cento de proteína. Pesos corporais foram avaliados no sétimo, vigésimo primeiro e septuagésimo dias de vida. Aos setenta dias de idade, cada grupo nutricional foi dividido em subgrupos: Nutrido-Salina (n=16) e Nutrido-Triptofano (n=16), Desnutrido-Salina (n=16) e Desnutrido-Triptofano (n=16). Os grupos receberam diariamente 1,0mL/100g de triptofano, na dose de 50mg/kgP ou salina (0,9 por centoNaCl), durante 14 dias. Neste período foram realizados os estudos dos parâmetros do comportamento alimentar. Posteriormente obteve-se a média do consumo alimentar relativo e a média do ganho de peso relativo. As análises estatísticas foram feitas utilizando os testes t Student e ANOVA seguido de Tukey, com p<0,05. RESULTADOS: As ninhadas de mães alimentadas com dieta hipoproteica mantiveram pesos inferiores comparados com as ninhadas nutridas (p<0,01) até os setenta dias de vida. Os ratos nutridos tratados com triptofano (M=6,88, DP=0,05) reduziram a ingestão alimentar comparados aos nutridos salina (M=7,27, DP=0,08) (p<0,01). Contudo, não houve efeito sobre o ganho de peso. Entre os desnutridos nenhuma diferença foi encontrada. CONCLUSÃO: Nesse estudo, a restrição proteica neonatal alterou a evolução ponderal em ratos. Além disso, a desnutrição precoce tornou os ratos adultos resistentes aos efeitos inibitórios do triptofano sobre a ingestão alimentar.

OBJECTIVE: This study investigated the effects of tryptophan on the eating behavior of adult rats submitted or not to early malnutrition. METHODS: Sixty-four male Wistar rats were divided into nourished (n=32, casein=17 percent) and malnourished (n=32, casein=8 percent) according to the diet given to the dam during lactation. After weaning, all rats were fed a diet with a protein content of 23 percent. The rats were weighed on day 7, day 21 and day 70 after birth. On day 70 after birth, each nutritional group was divided into 4 subgroups: nourished-saline (n=16), nourished-tryptophan (n=16), malnourished-saline (n=16) and malnourished-tryptophan (n=16). The tryptophan groups were given 1.0mL/100g of tryptophan for 14 days, at a dosage of 50mg/kgw of body weight and the saline groups were given 1.0mL/100g of 0.9 percent NaCl, also for 14 days. The eating behavior parameters were assessed during this period. The mean relative food intake and mean relative weight gain were then determined. The statistical analyses were done by the Student's t-test and ANOVA, followed by the Tukey test, with p<0.05. RESULTS: During the first 70 days of life, pups from protein-malnourished damns remained lighter than pups from well-nourished damns (p<0.01). Well-nourished rats treated with tryptophan (M=6.88, SD=0.05) ate less than those given saline (M=7.27, SD=0.08) (p<0.01) but weight was unaffected. No difference was found for the malnourished rats. CONCLUSION: In this study, neonatal protein restriction affected weight gain in rats. Furthermore, early malnutrition made adult rats resistant to the inhibitory effects of tryptophan on food intake.

Stress/aggressiveness-induced immune changes are altered in adult rats submitted to neonatal malnutrition.

BACKGROUND/AIMS: Neonatal malnutrition induces metabolic and endocrine changes that have beneficial effects on the neonatal in the short term but, in the longer term, these alterations lead to maladaptations. We investigated the effect of neonatal malnutrition on immune responses in adult rats submitted or not to an aggressiveness test. METHODS: Male Wistar rats were distributed to one of two groups according to their mothers' diet during lactation: the well-nourished group (group C, n = 42, receiving 23% of protein) and the malnourished group (group MN, n = 42, receiving 8% of protein). After weaning, all rats received normoproteic diet. Ninety days after birth, each group was subdivided into three subgroups: control rats (n = 14, respectively), aggressive rats (n = 14, respectively) and rats receiving foot shock (FS; n = 14, respectively). Plasma corticosterone concentration was measured after FS sessions. Leukocyte counts and humoral immunity were evaluated. RESULTS: In neonatal malnourished animals, FS-induced stress reduced plasma corticosterone concentration. Intraspecific aggressiveness induced alterations in leukocyte counts and antibody titers 7 and 15 days after immunization. Neonatal malnourished animals showed no changes in the immune parameters evaluated. CONCLUSIONS: Expression of intraspecific aggressiveness activates the immune system. Neonatal malnutrition seems to have a long-lasting effect on components of both neuroendocrine and immune functions.

Differential effects on somatic and reflex development by chronic clomipramine treatment.

The developmental effect of altered 5-HT and NE levels is a subject that requires more attention, especially when considering the increased demand for antidepressive dual reuptake inhibitors. Serotonin and norepinephrine are bioamines that differentially influence the nervous tissue growth. This study investigated the somatic maturation and the ontogeny of reflexes in neonate rats treated from the 1st to the 21st postnatal day (PND) with clomipramine (20 mg/kg sc, daily), a potent monoamine reuptake inhibitor. Indicators of both general body growth (body weight, axis of the head and body lengths) and physical maturation (ear unfolding, auditory conduit opening, eruption of the lower incisors and eye opening) were appraised. Ontogeny of motor and sensory reflexes (righting, free-fall righting--acceleration, negative geotaxis, cliff avoidance, auditory startle response and vibrissa placing) was also observed. The results demonstrated that chronic neonatal treatment with clomipramine alters the somatic growth. However, it did not interfere with the onset time of many physical features and reflexes. These results provide insights into the consequences of dual transmitter during early development.

Neonatal treatment with citalopram, a selective serotonin reuptake inhibitor, alters the growth of organs in rats

A serotonina (5-HT) desempenha várias funções, além de agir como fator trófico em tecidos nervoso e não nervosos durante o crescimento de órgãos. substâanacias utilizadas como antidepressivos, como citalopram, inibem seletivamente a recaptação da serotonina. O presente trabalho investiga o efeito do tratamento neonatal com citalopram sobre o crescimento de órgão em ratos. Ratos neonatos tratados, do 1§ao 21§ dia pós-natal (período de rápido crescimento do SN), com citalopram, na dose de 20mg/kg, foram sacrificados aos 120 dias de vida, sendo pesados i encéfalo, o fígado, o baço, o coração, os pulmões, o rim esquerdo e o testículo esquerdo. o tratamento neonatal com inibidor seletivo de recaptação da serotonina (ISRS) acarretou redução dos pesos absolutos de todos os órgãos. Houve aumento dos pesos relativos do encéfalo e do testículo, úmido e seco. Além disso, ocorreu aumento do peso relativo do rim seco e do pulmão úmido. Nestas condições experimentais, o inibidor seletivo de recaptura da serotonina alterou o crescimento dos órgãos estudados. Estes dados parecem corroborar o importante papel trófico da serotonina no desenvolvimento de tecidos. Contudo, é possível uma ação não específica do instrumento farmacológico utilizado

Depressäo: repercussões no sistema serotoninérgico / Depression: Repercussions in the serotoninergic system

Os autores indicam os problemas encontrados no estudo científico da depressão. Eles descrevem as principais alterações do sistema serotoninérgico na depressão humana e nos modelos experimentais de depressão, relatados na literatura. Concluem que o distúrbio do sistema de neurotransmissão serotoninérgico com certeza não é o único envolvido na depressão, mas é seguramente muito importante nessa patologia

Tratamento com inibidor de recaptura de serotonina, no período neonatal, reduz agressividade intraespecífica em ratos adultos / Neonatal treatment with selectiv serotonin reuptake inihibitor reduces intraespecific aggression in rats

A maioria dos estudos sugerem que serotonina (5_HT) inibe agressão em ratos. O tratamento com inibidor de recaptura de serotonina aumenta sua disponibilidade sináptica no cérebro. Entretanto as consequências deste tratamento durante o período pós-natal sobre as respostas agressivas na vida adulta não são claras. No presente trabalho, os autores investigaram o comportamento agressivo de ratos adultos tratados com citalopram, um potente inibidor de recaptura de serotonina, durante o aleitamento. Os resultados indicaram que a administração repetida de citolopram no início da vida diminuiu o ganho de peso no período pós-natal e reduz o comportamento agressivo de ratos adultos