RESUMO
Galactoglucomannan (GGM) is the predominant hemicellulose in coniferous trees, such as Norway spruce, and has been used as a multipurpose emulsifier in the food industry. In vitro digestion with a cellular antioxidant activity assay was performed to determine the bioaccessibility and antioxidant activity of phenolic compounds, and the behaviour of GGM on in vivo experimental assay against induced colon cancer. The results showed that digestion decreased the bioaccessibility and antioxidant capacity of phenolic compounds. Cellular analysis did not support these findings once an antioxidant effect was observed in human cell lines. GGM attenuated the initiation and progression of colon cancer, by reducing the foci of aberrant crypts in rats, and modified the intestinal bacterial microbiota (disrupting the balance between Firmicutes and Bacteroidetes phyla). Thus, GGM provided chemopreventive protection against the development of colon cancer and acted as an intracellular antioxidant agent.
Assuntos
Antioxidantes , Neoplasias do Colo , Microbioma Gastrointestinal , Mananas , Estresse Oxidativo , Humanos , Animais , Neoplasias do Colo/prevenção & controle , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Estresse Oxidativo/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Ratos , Antioxidantes/farmacologia , Mananas/farmacologia , Mananas/química , Masculino , Linhagem Celular TumoralRESUMO
This study explored the effects of fructose-induced obesity and metabolic disorders on peripheral inflammatory hyperalgesia, employing quantitative sensory testing with the von Frey test and measuring paw edema to assess inflammatory responses. Wistar rats were administered water or 10% fructose solution ad libitum over a period of 5 weeks. After intraplantar administration of inflammatory agents such as carrageenan (1 mg/paw), lipopolysaccharide (LPS; 100 µg/paw), or prostaglandin E2 (PGE2, 100 ng/paw), we conducted mechanical hyperalgesia tests and paw edema evaluations. The fructose diet resulted in dyslipidemia, elevated insulin and leptin plasma levels, insulin resistance, and increased epididymal and retroperitoneal adiposity compared to control animals. In response to inflammatory agents, the fructose group displayed significantly enhanced peripheral hyperalgesia and more pronounced paw edema. Our results demonstrate that fructose not only contributes to the development of obesity and metabolic disorder but also exacerbates peripheral inflammatory pain responses by enhancing prostaglandin sensitivity.
Assuntos
Frutose , Hiperalgesia , Ratos Wistar , Animais , Frutose/efeitos adversos , Frutose/administração & dosagem , Masculino , Hiperalgesia/metabolismo , Ratos , Inflamação/metabolismo , Inflamação/induzido quimicamente , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Carragenina , Dinoprostona/metabolismo , Dinoprostona/sangue , Edema/induzido quimicamente , Resistência à Insulina/fisiologia , Lipopolissacarídeos/toxicidade , Modelos Animais de DoençasRESUMO
Sickness behavior reflects a state of altered physiology and central nervous system function that occurs during systemic infection or inflammation, serving as an adaptive response to illness. This study aims to elucidate the role of hydrogen sulfide (H2S) in regulating sickness behavior and neuroinflammatory responses in a rat model of systemic inflammation. Adult male Wistar rats were treated with lipopolysaccharide (LPS) to induce sickness behavior. Intracerebroventricular (i.c.v.) pretreatments included aminooxyacetic acid (AOAA), an inhibitor of H2S synthesis, and sodium sulfide (NaHS), an H2S donor. Behavioral assays were conducted, along with the assessment of astrocyte activation, as indicated by GFAP expression in the hypothalamus. Pretreatment with NaHS mitigated LPS-induced behavioral changes, including hypophagia, social and exploratory deficits, without affecting peripheral cytokine levels, indicating a central modulatory effect. AOAA, conversely, accentuated certain behavioral responses, suggesting a complex role of endogenous H2S in sickness behavior. These findings were reinforced by a lack of effect on plasma interleukin levels but significant reduction in GFAP expression. Our findings support the central role of H2S in modulating neuroinflammation and sickness behavior, highlighting the therapeutic potential of targeting H2S signaling in neuroinflammatory conditions.
Assuntos
Sulfeto de Hidrogênio , Sulfetos , Ratos , Masculino , Animais , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Lipopolissacarídeos/toxicidade , Comportamento de Doença , Ratos Wistar , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Ácido Amino-Oxiacético/farmacologia , NeurotransmissoresRESUMO
Maternal immune activation (MIA) caused by exposure to pathogens or inflammation during critical periods of gestation increased susceptibility to neurodevelopmental disorders, including autism, in the offspring. In the present work, we aimed to provide characterization of the long-term consequences on anxiety-like behavior and cardiovascular stress response of MIA in the offspring. This study aimed to evaluate the effect of MIA by lipopolysaccharide (LPS) in adult male offspring. In our study, the animals were subjected to a range of behavioral and physiological tests, including the elevated plus maze, social interaction, cat odor response, open field behavior, contextual fear conditioning, and cardiovascular responses during restraint stress. In the offspring of MIA, our study unveiled distinct anxious behaviors. This was evident by fewer entries into the open arms of the maze, diminished anti-thigmotaxis in the open field, and a decrease in social interaction time. Moreover, these rats showed heightened sensitivity to cat odor, exhibited prolonged freezing during fear conditioning, and presented elevated 22 Hz ultrasonic vocalizations. Notably, during restraint stress, these animals manifested an augmented blood pressure response, and this was associated with an increase in c-fos expression in the locus coeruleus compared to the control group. These findings collectively underline the extensive behavioral and physiological alterations stemming from MIA. This study deepens our understanding of the significance of maternal health in predisposing offspring to neurobehavioral deficits and psychiatric disorders.
Assuntos
Transtorno Autístico , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Ratos , Masculino , Animais , Comportamento Animal/fisiologia , Capacidades de Enfrentamento , Modelos Animais de Doenças , Poli I-C/farmacologiaRESUMO
Dillenia indica (Linn.) has been reported by several biological activities, including anti-inflammatory, antioxidant, antidiabetic, anti-hyperglycemic, antiproliferative, antimutagenic, anticholinesterase, and antimicrobial. In Brazilian traditional medicine, the fruits of D.â indica have been used to treat general topical pain and inflammation, but with no scientific validation. Thus, aiming to study its chemical constitution and antinociceptive properties, the crude extract (CE) and fractions obtained from the fruits of D.â indica were submitted to an inâ vivo pharmacological evaluation and a dereplication study by LC-MS/MS analysis, assisted by the Global Natural Product Social Molecular Networking (GNPS). The oral antinociceptive activity of the fruits of D.â indica and the possible participation of the opioid and cannabinoid systems were demonstrated in the formalin-induced nociception model. The chemical dereplication study led us to identify several known chemical constituents, including flavonoids, such as caffeoylmalic acid, naringenin, quercetin, and kaempferol. According to literature data, our results are compatible with significant antinociceptive and anti-inflammatory activities. Therefore, the flavonoid constituents of the fruits of D.â indica are probably responsible for its antioxidant, anti-inflammatory, and antinociceptive effects mediated by both opioid and cannabinoid systems, confirming its folk use in the treatment and relief of pain.
Assuntos
Analgésicos , Dilleniaceae , Analgésicos/química , Analgésicos Opioides/efeitos adversos , Extratos Vegetais/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Anti-Inflamatórios/farmacologia , Dor/tratamento farmacológico , Flavonoides/uso terapêuticoRESUMO
AIMS: The present study was developed to investigate how litter reduction-induced obesity promotes early depressive-related behaviors in rodent offspring. MAIN METHODS: We employed a standardized litter size reduction protocol, dividing litters into groups: normal litters (NL), consisting of six males and six females pups and small litters (SL), comprising two males and two females pups. Maternal behavior was monitored during the initial week of lactation. Subsequently, we assessed the pups for weight gain, locomotor activity, social play behavior, and performance in forced swimming test. We further evaluated the weights of retroperitoneal and perigonadal fat tissues, along with the expression of glial fibrillary acidic pprotein (GFAP) in the hippocampus and prefrontal cortex of the offspring. KEY FINDINGS: Our results indicated that litter size reduction led to an increased the maternal behavior. In contrast, offspring from the SL group displayed greater weight gain and increased, retroperitoneal and perigonadal fat. Both male and female rodents in the SL group exhibited decreased social play behavior, and male offspring spent more time immobile during the forced swimming test, suggesting a depressive-like phenotype. Notably, we observed an increase in the GFAP expression in the prefrontal cortex of male rodents, with a trend toward increased expression in the hippocampus. SIGNIFICANCE: Obesity may facilitate the development of early depressive-like behaviors, potentially associated with elevated GFAP expression in the prefrontal cortex.
Assuntos
Tecido Adiposo , Obesidade , Animais , Feminino , Masculino , Gravidez , Tecido Adiposo/metabolismo , Tamanho da Ninhada de Vivíparos , Obesidade/metabolismo , Córtex Pré-Frontal , Aumento de PesoRESUMO
Ring-substituted phenethylamines are believed to induce psychedelic effects primarily by interacting with 5-hydroxytryptamine 2 (5-HT2A) receptors in the brain. We assessed the effect of the psychedelic substances 25H-NBOMe and 25H-NBOH on the depressive-like behavior of male adult rats. Naive Wistar rats were divided into groups to assess the effects of different doses (0.1 mg/kg, 1 mg/kg, and 3 mg/kg) of 25H-NBOMe and 25H-NBOH. The substances were administered intraperitoneally and the hallucinogenic properties were evaluated using the head twitch response test (HTR). Additionally, we assessed their locomotor activity in the open field test (OFT) and depressive-like behavior in the forced swimming test (FST). Our data demonstrated that all doses of synthetic psychedelic substances evaluated exhibited hallucinogenic effects. Interestingly, we observed that both 25H-NBOMe and 25H-NBOH produced a significantly greater motivation to escape in the FST, compared to the control group. Furthermore, we found no significant differences in locomotor activity during the OFT, except for the dose of 3 mg/kg, which induced a reduction in locomotion. This study provides new insights into a potential psychedelic substance, specifically by demonstrating the previously unknown antidepressant properties of a single dose of both 25H-NBOMe and 25H-NBOH. These findings contribute to the ongoing progress of experimental psychiatry toward developing safe and effective clinical practices in the field of psychedelics research.
Assuntos
Alucinógenos , Ratos , Masculino , Animais , Alucinógenos/farmacologia , Ratos Wistar , Antidepressivos/farmacologia , Fenetilaminas/farmacologia , NataçãoRESUMO
Blackcurrant press cake (BPC) is a source of anthocyanins, and this study evaluated the bioactivity and gut microbiota modulation of blackcurrant diets with or without 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis in rats. In colon cancer-induced rats (CRC), BPC at the highest dosages increased pro-inflammatory parameters and the expression of anti-apoptotic cytokines, accentuating colon cancer initiation by aberrant crypts and morphological changes. Fecal microbiome analysis showed that BPC altered the composition and function of the gut microbiome. This evidence suggests that high doses of BPC act as a pro-oxidant, accentuating the inflammatory environment and CRC progression.
Assuntos
Neoplasias do Colo , Microbiota , Animais , Ratos , Antocianinas/farmacologia , Estresse Oxidativo , Inflamação , Veículos FarmacêuticosRESUMO
Gestational hypothyroidism is a prevalent disorder in pregnant women and also impairs fetal development with relevant outcomes. One of the outcomes of greatest interest has been rodent fear- and anxiety-like behavior. However, the relationship between maternal hypothyroidism and onset of conditioned fear-related responses in offspring remains controversial. Here, we used a well-validated methimazole-induced gestational hypothyroidism to investigate the behavioral consequences in offspring. Dams were treated with methimazole at 0.02% in drinking water up to gestational Day 9. Maternal body weights and maternal behavior were evaluated, and the puppies ware analyzed for weight gain and physical/behavioral development and assigned for the open field and fear conditioning test. Methimazole-induced gestational hypothyroidism induced loss in maternal and litter weight, increases in maternal behavior, and impairs in offspring developmental landmarks in both male and female rodents. Only male offspring enhanced responsiveness to conditioned fear-like behavior in adulthood.
Assuntos
Hipotireoidismo , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Animais , Gravidez , Masculino , Cães , Metimazol/toxicidade , Roedores , Hipotireoidismo/induzido quimicamente , Ansiedade/induzido quimicamente , Medo , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamenteRESUMO
Glyphosate is the organophosphate pesticide most widely used in the world. Recent studies correlate exposure to glyphosate and the emergence of neurodevelopmental disorders. Therefore, it was objective to propose a rat model of perinatal exposure to glyphosate-based herbicides (GBH) to study associated neurodevelopmental disorders. Behavioral aspects and brain pathways were assessed in the prepubertal phase. For this, maternal treatment occurred throughout the entire gestation period (from GD0) until weaning on postnatal day 22 (PND 22). Control group received oral gavage with 5 mL/kg of saline per day and GBH group received oral gavage with 50 mg/kg of GBH per day (n = 10 per group). Maternal behavior was evaluated in PND 2-6. Offspring were evaluated for quantification of ultrasonic vocalizations (PND 5); homing behavior test (PND 13); and hole board, social play behavior, open field, and object recognition tests (PND 28-32). Prefrontal cortex and hippocampus of the offspring were processed to evaluate oxidative stress. Maternal exposure to GBH impaired early social communication, olfactory discrimination, social play behavior, and the exploration of objects, in addition to increasing repetitive and stereotyped movements. GBH also increased oxidative stress. Therefore, perinatal GBH exposure induced behavioral and oxidative stress impairments in rats associated with neurodevelopmental disorders. The manifestations found in the offspring are in accordance with symptoms of autism spectrum disorder.
Assuntos
Transtorno do Espectro Autista , Herbicidas , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Glicina/análogos & derivados , Herbicidas/toxicidade , Hipocampo , Humanos , Organofosfatos , Estresse Oxidativo , Córtex Pré-Frontal , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Wistar , GlifosatoRESUMO
Lipopolysaccharide (LPS) is a potent inducer of inflammation, triggering behavioral changes and fever. The present study aimed to evaluate whether pretreatment with curcumin prevents the behavioral changes and fever induced by LPS through the modulation of nuclear factor-erythroid 2 related factor 2 (Nrf2). Male Wistar rats received either vehicle or LPS and after 2 h, the behavioral responses were assessed through open field test (OFT), social interaction test, forced swim test (FST), and food intake assessment. The febrile response was assessed by telemetry after vehicle or LPS injection to evaluate the effect of curcumin on the thermoregulatory response during the immunological challenge. The pretreatment with curcumin at doses of 50 and 100 mg/kg prevented the reduction of distance traveled on OFT, increased the immobility time of FST, impaired social withdrawal, decreased food intake, and induced fever. In addition, at these doses, it was possible to observe a significant decrease in the plasma levels of cytokines and an increase in Nrf2 translocation to the cell nucleus during the immunological challenge. Our data provide further evidence of curcumin's ability to prevent LPS-induced sickness behavior and fever possibly by a mechanism related to the modulation of Nrf2 translocation.
Assuntos
Curcumina , Comportamento de Doença , Fator 2 Relacionado a NF-E2 , Animais , Curcumina/farmacologia , Febre/induzido quimicamente , Febre/tratamento farmacológico , Febre/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos WistarRESUMO
AIMS: During illnesses caused by infectious diseases, a suite of brain-mediated responses called sickness syndrome occurs, triggering behavioral and physiological changes. This study investigated whether ghrelin modulates sickness syndrome induced by systemic administration of lipopolysaccharide (LPS). MAIN METHODS: Male Wistar rats were pretreated with vehicle or [D-lys3]-GHRP-6, a ghrelin receptor GHS-R1 antagonist (20 nmol, i.c.v), 30 min before injection of LPS (200 µg/kg, i.p.) or sterile saline. We investigated the behavioral effects in male rats after LPS administration by screening for depressive-like behavior, locomotor activity alterations, and corticosterone release. Changes in body temperature were measured using a biotelemetry probe preimplanted in the peritoneal cavity to evaluate the effect of ghrelin on the thermoregulatory response during immunological challenge. KEY FINDINGS: Pretreatment with [D-lys3]-GHRP-6 blunted most of the assessed parameters related to sickness syndrome, including social withdrawal, anhedonia, depressive-like behavior, and anorexia, reduced the activation of the HPA axis, but did not alter LPS-induced fever. SIGNIFICANCE: Our findings suggest that ghrelin centrally mediates the sickness behavior and activation of HPA, as a ghrelin receptor antagonist attenuates social withdrawal, anhedonia, depressive-like behavior, anorexia, and HPA activation in response to LPS.
Assuntos
Sistema Hipotálamo-Hipofisário/fisiologia , Comportamento de Doença/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Transtornos Mentais/prevenção & controle , Oligopeptídeos/farmacologia , Receptores de Grelina/antagonistas & inibidores , Animais , Temperatura Corporal , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Comportamento de Doença/fisiologia , Locomoção , Masculino , Transtornos Mentais/induzido quimicamente , Transtornos Mentais/metabolismo , Transtornos Mentais/patologia , Ratos , Ratos WistarRESUMO
Individuals with post-traumatic stress disorder (PTSD) show increased rates of several serious metabolic diseases. However, little is known about pre-existing metabolic diseases and the development of PTSD. Therefore, we aimed to evaluate the course of post-traumatic stress disorder (PTSD) development in rats with preexisting diabetes. In addition, we quantified glial fibrillary acidic protein (GFAP) in the hippocampus of the experimental animals. For this, we used male Wistar rats and divided them into two groups: saline and alloxan (150 mg/Kg, i.p.). The animals were weighed, and plasma glucose was measured after 48 h of diabetes induction by alloxan. The animals were either exposed to inescapable footshocks or not, followed by social isolation. After 14 days, the animals were re-exposed to the box, and the freezing time was evaluated for 10 min. Over the following days, the animals were tested on the open field, social interaction and forced swimming tests. In another group of animals, elevated plus maze and object recognition tests were performed. Our results demonstrated that animals with diabetes had more pronounced PTSD-like symptoms as a reduction in social interaction, an increase in immobility time in forced swimming, a reduction in permanence in the open arms of the elevated plus maze, and a deficit in the object recognition index more accentuated. However, this did not reflect astrocyte activation in the hippocampus. In conclusion, diabetes accentuates post-traumatic stress disorder-like symptoms but not astrocyte activation in the hippocampus.
Assuntos
Astrócitos/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hipocampo/metabolismo , Transtornos de Estresse Pós-Traumáticos/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Ratos , Ratos Wistar , Transtornos de Estresse Pós-Traumáticos/complicaçõesRESUMO
Maternal infection during pregnancy is an environmental risk factor for neurodevelopmental dysfunction, such as autism spectrum disorder (ASD). This study investigated the effect of maternal immune activation (MIA) on the behavior profile of prepubertal offspring and whether MIA alters the neuronal activation pattern of brain areas related to social play behavior. Pregnant Wistar rats received 500 µg/kg of lipopolysaccharide or saline solution on gestational day 16. Their offspring were tested using behavioral tasks to capture some of the core and associated ASD-like symptoms. Neuronal activation, indexed via c-fos expression after social play behavior, was evaluated in several brain areas. MIA had a number of adverse effects on dams and reduced the number of successful births and litter size. MIA induced sex-specific autistic-like features by a reduction in ultrasonic vocalizations in response to separation from the mother and nest, reduction in discrimination between neutral odors and their nest odor, moderate effect in stereotypies in the hole-board test, impaired risk assessment phenotype, and reduction in social play behavior without changes in locomotor activity only in prepubertal male offspring. A decrease in social play behavior may be associated with a decrease in the number of c-fos-positive cells in the prefrontal cortex and striatum, but hyperactivation of the basolateral and basomedial amygdala. Prenatal immune challenge results in ASD-like symptoms such as impaired risk assessment behavior, communication, and social interactions in male prepubertal offspring. Impaired social play behavior is correlated with neuronal hyperactivation in the amygdala.
Assuntos
Tonsila do Cerebelo , Transtorno do Espectro Autista/fisiopatologia , Comportamento Animal/fisiologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Caracteres Sexuais , Comportamento Social , Fatores Etários , Tonsila do Cerebelo/imunologia , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos WistarRESUMO
Exposure to stress might influence pain sensitivity; however, little is known about whether post-traumatic stress disorder (PTSD)-like symptoms alter pain sensitivity and how it can happen. Male rats were exposed to the inescapable footshock paired with either social isolation or a control condition (not exposed to footshock but subjected to social isolation). After 7, 14, or 21 days, memory retention was evaluated. In the following three days, animals underwent the following tests: open-field, social interaction and formalin tests. Another group of animals were subjected to the object recognition test and to von Frey filaments. In other cohorts of animals, saline, fluoxetine, or desipramine were injected intrathecally and immunohistochemistry was performed to investigate whether PTSD-like symptoms alter the expression of c-Fos in serotonergic and noradrenergic neurons. Inescapable footshock induced the development of PTSD-like symptoms. Animals with PTSD-like symptoms showed an increase in the number of flinches in the formalin test and a reduction in mechanical threshold in the von Frey test at both retention intervals. The social interaction was negatively correlated with the nociceptive response in the formalin test. Fluoxetine or desipramine prevented the nociceptive response to chemical stimulus in the formalin test. In addition, in animals with PTSD-like symptoms, there was a reduction in c-Fos expression in serotonergic and noradrenergic neurons. Our results are important for the association of increased sensitivity to pain as one of the clinical manifestations that are present in the development of PTSD, and a possible treatment for increased pain sensitivity in male individuals with PTSD.
Assuntos
Dor/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Neurônios Adrenérgicos/metabolismo , Neurônios Adrenérgicos/fisiologia , Animais , Comportamento Animal , Fluoxetina/farmacologia , Masculino , Norepinefrina/metabolismo , Dor/metabolismo , Manejo da Dor/psicologia , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Wistar , Neurônios Serotoninérgicos/metabolismo , Neurônios Serotoninérgicos/fisiologia , Comportamento Social , Transtornos de Estresse Pós-Traumáticos/metabolismoRESUMO
AIMS: We assessed the influence of maternal overweight on the behavioral neurodevelopment of male and female offspring in prepubertal age by reducing the litter size. MAIN METHODS: To reduce litter size in Wistar rats, the offspring of generation 0 (G0) were culled for 12 pups (6 males and 6 females: normal litter, NL-G1) or 4 pups (2 males and 2 females: small litter, SL-G1). In G1 dams, overweight was characterized, maternal behavior and locomotor activity were assessed. At G2, we quantified the ultrasonic vocalizations in post-natal day 5 (PND5); we evaluated olfactory discrimination in the homing behavior test on PND13; and in PND28-32 (prepubertal age), we performed the following tests: social play behavior, hole board, object recognition, and open field. At the end of the experiments, hippocampus and prefrontal cortex were dissected to quantify the synaptophysin by western blotting. KEY FINDINGS: Our data demonstrated that a reduction in litter size was able to induce maternal overweight without altering the parameters related to overweight in the offspring. The SL-G2 offspring showed deficits in early social communication, olfactory discrimination, social play behavior, and the exploration of objects, in addition to increasing repetitive and stereotyped movements. There were also changes in the synaptophysin levels in the hippocampus and prefrontal cortex of the offspring from reduced litter dams. In conclusion, maternal overweight caused by litter reduction impairs behavioral neurodevelopment, inducing autism-like symptoms in the offspring. SIGNIFICANCE: This study alerts the public about the negative consequences of maternal overweight in the descendants.
Assuntos
Comportamento Materno/fisiologia , Transtornos do Neurodesenvolvimento/etiologia , Sobrepeso/fisiopatologia , Animais , Animais Recém-Nascidos , Peso Corporal , Encéfalo/metabolismo , Feminino , Hipocampo/metabolismo , Tamanho da Ninhada de Vivíparos/fisiologia , Masculino , Transtornos do Neurodesenvolvimento/fisiopatologia , Fenômenos Fisiológicos da Nutrição/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos WistarRESUMO
Campomanesia xanthocarpa popularly known as gabiroba is used as a medicinal plant for the treatment of inflammatory diseases, ulcers, among other uses, requiring studies to assist in proving these activities. In this study, the extract of leaves from C. xanthocarpa (CxHE) was submitted to assays of formalin-induced paw-licking, peritonitis induced by lipopolysaccharide and carrageenan-induced mechanical hyperalgesia tests. In chemical analysis, a preliminary phytochemical screening and the determination of phenol and flavonoid content were carried out, in addition to analysis by ESI-MS/MS system and HPLC-DAD system. The CxHE presented compounds such as tannins, triterpenoids, steroids and saponins and content of phenols (35.9 ± 1.3 GAE/g extract) and flavonoids (23.3 ± 2.1 mg EQ/g extract). Protocatechuic acid, gallic acid, ethyl gallate, quercetin, and 3-methyl epigallocatechin gallate, alpha and beta-amyrins were identified. CxHE at doses of 10-1000 mg/kg p.o. demonstrated anti-inflammatory and antinociceptive effects in all in vivo assays employed in this study. [Figure: see text].
Assuntos
Extratos Vegetais , Espectrometria de Massas em Tandem , Analgésicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de PlantaRESUMO
Exposure to stressful environmental events during the perinatal period can increase vulnerability to psychopathologies that cause neuroendocrine changes associated with deficits in emotional behavior that can appear early in life. Post-traumatic stress disorder (PTSD) is a frequent, chronic, and disabling disorder that negatively impacts the emotional, social, and cognitive behaviors of affected individuals. Thus, we induced PTSD in pregnant rats by applying inescapable footshocks and then investigated the behavioral parameters similar to anxiety in offspring at prepubertal age, in addition to the plasma levels of maternal and offspring corticosterone and expression of glucocorticoid receptors (GR) in the offspring's hippocampus. With the dams, maternal behavior, open field, and object recognition tests were performed. With the male and female offspring, we performed the following: quantification of ultrasonic vocalizations, elevated plus-maze test, evaluation of exploratory activity in the open field, and hole board test, as well as plasma corticosterone measurements and Western blotting for GR. Our results showed that gestational PTSD affected maternal behavior, led to anxiety-like symptoms, increased corticosterone levels, and increased GR expression in the offspring's hippocampus. Therefore, our data can contribute to the understanding of the onset of early (childhood and juvenile/pre-pubertal phases) anxiety owing to exposure to a traumatic event during the gestation period.
Assuntos
Ansiedade , Comportamento Animal/fisiologia , Corticosterona/metabolismo , Comportamento Materno/fisiologia , Efeitos Tardios da Exposição Pré-Natal , Receptores de Glucocorticoides/metabolismo , Transtornos de Estresse Pós-Traumáticos/complicações , Animais , Ansiedade/etiologia , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Feminino , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos WistarRESUMO
Overfeeding and rapid weight gain during early life are risk factors for the development of obesity in adulthood. This metabolic malprogramming may be mediated by endocrine disturbances during critical periods of development. Cholecystokinin (CCK) acts on the central nervous system by elevating thermogenesis and the activity of anorectic neurons, modulating overall energy balance. Therefore, we tested the hypothesis that postnatal overfeeding impaired CCK effects. Pups were raised in either a litter of three (neonatal overnutrition/small litter group) or 12 (controls/normal litter group) pups per dam to study the effects of postnatal overfeeding on the central and peripheral CCK systems in adulthood. Rats raised in small litters became overweight during lactation and remained overweight as adults, with increased adiposity and plasma levels of lipids, glucose, insulin, and leptin. Neonatally over-nourished rats showed attenuation of gastric emptying and anorexigenic response to CCK, suggesting that offspring from the SL group may present CCK resistance as adult male rats. Consistent with this idea, overweight rats displayed impaired central response in c-Fos immunoreactivity on the nucleus tractus solitarius, area postrema, paraventricular nucleus, central amygdala, arcuate nucleus, and dorsomedial hypothalamus in response to peripheral CCK at adulthood. The small litter group of adult male rats also exhibited reduced norepinephrine- and CCK-stimulated thermogenesis. Unresponsiveness to the effects of CCK may contribute to overweight and metabolic dysfunctions observed in postnatally over-nourished adult rats. Thus, the involvement of an impaired CCK system, among other neurohormonal failures, may contribute to the development of obesity.
Assuntos
Adiposidade , Sistema Nervoso Central/fisiopatologia , Colecistocinina/metabolismo , Sistema Endócrino/fisiopatologia , Hipernutrição/fisiopatologia , Tecido Adiposo/metabolismo , Animais , Animais Recém-Nascidos , Mapeamento Encefálico , Metabolismo Energético , Feminino , Esvaziamento Gástrico , Glucose/metabolismo , Homeostase , Hipotálamo , Leptina/sangue , Lipídeos/química , Masculino , Obesidade/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Termogênese , Aumento de PesoRESUMO
Prenatal ethanol exposure affects brain development and causes neural impairment, leading to both cognitive and behavioral consequences in the offspring. Therefore, the aim of this study was to investigate the impact of prenatal exposure to small amounts of alcohol on social play behavior in adolescent male offspring. Swiss mice were prenatally exposed to ethanol by feeding pregnant dams with a liquid diet containing 25% alcohol-derived calories during gestation (alcohol group). They were then compared to both pair-fed dams that received an isocaloric liquid diet containing 0% alcohol-derived calories (pair-fed group) and dams with ad libitum access to a liquid control diet (control group). Additionally, maternal behavior was evaluated in terms of neural activation indexed via c-fos expression in the prefrontal cortex. Although dams exposed to alcohol during pregnancy did not alter their maternal behavior, the offspring presented a decrease in their social play behavior compared with both control and pair-fed offspring. The decrease in social play behavior may be associated with a decrease in number of c-fos-positive cells in the prefrontal cortex. The exposure to small amounts of alcohol during intrauterine development causes both a deficit in social play behavior and a reduction in the neuronal activity seen in the prefrontal cortex.