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1.
Behav Genet ; 40(4): 467-79, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20238238

RESUMO

Cortisol is an indicator of hypothalamic-pituitary-adrenal axis responsivity to stress, but few twin studies have examined the heritability of cortisol concentrations in adults across the diurnal cycle and in different contexts. Saliva samples were provided by 783 middle-aged male twins on one laboratory and two home days as part of the Vietnam Era Twin Study of Aging. Significant cortisol heritability estimates were found for laboratory measures only: awakening (.56); 30 min after awakening (.48); 1000 h (.42); mean output across the day (.43); and mean cortisol awakening response (.64). Twin correlations at home were low. In the laboratory, they were unchanged for fraternal twins, but increased for identical twins. Greater measurement error at home did not appear to account for home-laboratory differences. The results suggest that genetic factors influence cortisol responses to specific environmental stressors. Thus, cortisol levels are correlated in identical twins only when they undergo similar experiences.


Assuntos
Ritmo Circadiano/genética , Hidrocortisona/genética , Hidrocortisona/metabolismo , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Nível de Alerta , Ritmo Circadiano/fisiologia , Meio Ambiente , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiologia , Saliva/química , Fatores de Tempo
2.
Neurochem Res ; 35(11): 1743-6, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20680457

RESUMO

The median eminence of the hypothalamus is part of the avenue by which neurosecreted hormones from the hypothalamic nuclei reach the pars nervosa (neural lobe) of the pituitary and eventually the bloodstream. Lithium treatment and osmotic stress increases the transport of neurosecretory hormones to the pituitary in the adult rat. Specialized astrocytes termed pituicytes in the pars nervosa of the pituitary participate in the secretory process and also develop considerable mitotic activity. The present work reveals similar mitotic figures in cells within the median eminence following 3 days of lithium treatment. The location and appearance of these mitoses add to the evidence that pituicytes are present in the median eminence. Moreover, mitoses occur within the ependymal (tanycyte) layer of the median eminence. Thus, the present results suggest that the tanycyte layer may contain pituicytes, indicating that the hypothalamus possesses specialized cells for modulating neurosecretion in response to osmotic challenges.


Assuntos
Cloreto de Lítio/farmacologia , Eminência Mediana/ultraestrutura , Mitose , Animais , Feminino , Lítio/sangue , Masculino , Eminência Mediana/efeitos dos fármacos , Ratos , Ratos Endogâmicos Lew
3.
Exp Mol Pathol ; 86(1): 18-22, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19041304

RESUMO

Down's syndrome (DS) in humans is caused by trisomy of chromosome 21 (HSA 21). DS patients have a variety of pathologies, including mental retardation and an unusually high incidence of leukemia or lymphoma such as megakaryocytic leukemia. Individuals with DS develop the characteristic neuropathological hallmarks of Alzheimer's disease (AD) in early adulthood, generally by the fourth decade of life. There are several mouse models of DS that have a segmental trisomy of mouse chromosome 16 (MMU 16) with triplicated genes orthologous to HSA 21. These mice display neurodegeneration similar to DS. Although brain pathology in DS models is known, little information is available about other organs. We studied the extraneural pathology in aged DS mice (Ts65Dn, Ts2 and Ts1Cje aged 8 to 24 months) as well as other mouse models of neurodegeneration, including presenilin (PS), amyloid-beta precursor protein (APP), and tau (hTau and JNPL) transgenic mice. An increased incidence of peripheral amyloidosis, positive for amyloid A (AA) but not amyloid-beta peptide (A beta), was found in APP over-expressing and tauopathic mice as compared to non-transgenic (ntg) littermates or to DS mouse models. A higher incidence of lymphoma was found in the DS models, including Ts1Cje that is trisomic for a small segment of MMU 16 not including the App gene, but not in the APP over-expressing mice, suggesting that high APP expression is not the cause of lymphoma in DS. The occurrence of lymphomas in mouse DS models is of interest in relation to the increased incidence of malignant conditions in human DS.


Assuntos
Envelhecimento/patologia , Doença de Alzheimer/patologia , Modelos Animais de Doenças , Síndrome de Down/patologia , Envelhecimento/fisiologia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos Transgênicos , Miocárdio/citologia , Miocárdio/metabolismo , Miocárdio/patologia , Baço/citologia , Baço/metabolismo , Baço/patologia
4.
Dev Psychopathol ; 21(2): 579-91, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19338699

RESUMO

This study examines the relation between adolescents' antisocial behaviors and adrenocortical activity during a laboratory visit in a sample of economically disadvantaged families (N = 116, ages 12-14, 51% female). Pretask cortisol levels indexed adolescents' prechallenge response to the lab visit, whereas adolescents' response to a conflict discussion with their caregivers was indexed with residualized change in pre- to postconflict cortisol levels. A trait measure of antisocial behavior (derived from parent, teacher, and self-reports) was associated with lower pretask cortisol levels but greater cortisol response to the conflict discussion. Gender moderated antisocial adolescents' cortisol response to the conflict discussion with girls who reported more covert risky problem behaviors showing an increased cortisol response. The findings suggest that, although antisocial adolescents had lower pretask cortisol levels, conflict discussions with caregivers present a unique challenge to antisocial girls compared with antisocial boys.


Assuntos
Comportamento do Adolescente/psicologia , Transtorno da Personalidade Antissocial/metabolismo , Transtorno da Personalidade Antissocial/psicologia , Conflito Psicológico , Hidrocortisona/metabolismo , Desempenho Psicomotor , Adolescente , Fatores Etários , Cuidadores , Criança , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Fatores de Risco , Saliva/metabolismo , Fatores Sexuais , Análise e Desempenho de Tarefas
5.
Dev Psychobiol ; 51(1): 14-23, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18720365

RESUMO

Maltreated foster children are subjected to a range of early adverse experiences, including neglect, abuse, and multiple caregiver disruptions. Research suggests that such disturbances alter the development and subsequent functioning of the hypothalamic-pituitary-adrenocortical system. The current study was designed to investigate morning cortisol levels in 117 foster children and 60 low-income, nonmaltreated children. Maltreatment and foster care placement experiences were coded from official records. Analyses revealed that the foster children were significantly more likely than the nonmaltreated children to have low morning cortisol levels. Additionally, specific maltreatment experiences were significantly associated with the foster children's morning cortisol levels. Foster children with low morning cortisol levels experienced more severe physical neglect than the other foster children. In contrast, foster children with high morning cortisol levels experienced more severe emotional maltreatment. These results suggest that specific early adverse experiences have differential effects on the functioning of the hypothalamic-pituitary-adrenocortical system.


Assuntos
Maus-Tratos Infantis/diagnóstico , Maus-Tratos Infantis/estatística & dados numéricos , Ritmo Circadiano , Cuidados no Lar de Adoção/estatística & dados numéricos , Hidrocortisona/metabolismo , Criança , Pré-Escolar , Ritmo Circadiano/fisiologia , Diagnóstico Diferencial , Feminino , Humanos , Hidrocortisona/análise , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Saliva/química , Meio Social
6.
J Psychiatry Neurosci ; 33(3): 227-34, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18592041

RESUMO

OBJECTIVE: Autism is characterized by impairment in communication and social interaction, by repetitive behaviours and by difficulty in adapting to novel experiences. The objective of the current investigation was to replicate and extend our previous findings showing variable circadian rhythm and significant elevations in cortisol following exposure to a novel stimulus (mock magnetic resonance imaging [MRI]). METHODS: Circadian rhythms of cortisol were estimated in 22 children with and 22 children without autism via analysis of salivary samples collected in the morning, afternoon and evening over 6 separate days. We assessed hypothalamic-pituitary-adrenal (HPA) responsiveness by examining changes in salivary cortisol in response to a mock MRI. One-half of the children were re-exposed to the MRI environment. RESULTS: Children with autism showed a decrease in cortisol in the morning over 6 days while maintaining higher evening values. Children with autism also showed more within-and between-subject variability in circadian rhythms. Although the cortisol values tended to be higher in some of the children with autism, a statistically significant elevation in cortisol in response to the initial mock MRI was not observed. Rather, both groups showed heightened cortisol at the arrival to the second visit to the imaging centre, suggesting an anticipatory response to the re-exposure to the mock MRI. CONCLUSION: Children with autism showed dysregulation of the circadian rhythm evidenced by variability between groups, between children and within individual child comparisons. Both groups demonstrated increased salivary cortisol in anticipation of re-exposure to the perceived stressor.


Assuntos
Transtorno Autístico/metabolismo , Transtorno Autístico/psicologia , Ritmo Circadiano , Hidrocortisona/metabolismo , Estresse Psicológico/psicologia , Criança , Feminino , Humanos , Hidrocortisona/análise , Sistema Hipotálamo-Hipofisário/anatomia & histologia , Sistema Hipotálamo-Hipofisário/metabolismo , Imageamento por Ressonância Magnética , Masculino , Sistema Hipófise-Suprarrenal/anatomia & histologia , Sistema Hipófise-Suprarrenal/metabolismo , Saliva/química , Fatores de Tempo
7.
Prog Neuropsychopharmacol Biol Psychiatry ; 32(1): 29-33, 2008 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-18029073

RESUMO

Lithium treatment of patients and laboratory animals causes increased body weight but no single organ or system has been found responsible. In the present work, we showed that lithium increased the weight of the female rat's gastrointestinal (GI) tract including its contents. The weight gain of the female rat GI tract was the same order of magnitude as the weight gain of the whole body of the females. All three parts of the GI tract (stomach, small intestine, colon) participated in the weight gain. Lithium treatment of male rats also increased GI tract weight, but lithium did not increase their overall body weight because of loss of weight at other sites.


Assuntos
Antimaníacos/farmacologia , Peso Corporal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Cloreto de Lítio/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Caracteres Sexuais , Animais , Feminino , Trato Gastrointestinal/fisiologia , Masculino , Ratos
8.
Exp Mol Pathol ; 85(2): 117-21, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18675267

RESUMO

The four choroid plexuses in the brain ventricles are not identical, but differences among them have rarely been studied. The present work concerns the inflammatory and hemorrhagic choroid plexitis produced in Lewis rats by a single gavage of cholecalciferol (vitamin D(3)) or related steroids with vitamin D activity. Plexitis was very severe in the fourth ventricular plexus, somewhat less severe in the lateral ventricular plexuses, and almost absent in the third ventricular plexus. These findings were compared to the scanty data from the literature on differences among the plexuses.


Assuntos
Ventrículos Cerebrais/patologia , Colecalciferol/efeitos adversos , Plexo Corióideo/metabolismo , Inflamação/patologia , Vitaminas/efeitos adversos , Animais , Feminino , Masculino , Ratos , Ratos Endogâmicos Lew , Índice de Gravidade de Doença
9.
Dev Psychopathol ; 20(3): 845-59, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18606034

RESUMO

Studies with nonhuman primates and rodents, as well as with human children, have suggested that early separations from caregivers are often associated with changes in the functioning of the hypothalamus-pituitary-adrenal (HPA) axis. On the basis of these findings, we designed a relational intervention that was intended to normalize HPA functioning among children in foster care. This paper presents findings from a randomized clinical trial that assessed the effectiveness of a relational intervention (Attachment and Biobehavioral Catch-up [ABC]) with regard to HPA functioning. The ABC intervention was intended to enhance children's ability to regulate physiology and behavior. The control intervention (Developmental Education for Families) was intended to enhance children's cognitive skills. A comparison group of children who had never been in foster care was also included. Children's cortisol production was assessed upon arrival at the lab, and 15 and 30 min following the Strange Situation. Random effects analyses of variance were performed to assess differences in initial values and change between children in the two intervention groups. Children in the ABC intervention and comparison group children showed lower initial values of cortisol than children in the treatment control group, considering arrival at lab as initial values (p < .05). Groups did not differ significantly in change over time. These results suggest that the ABC intervention is effective in helping children regulate biology in ways more characteristic of children who have not experienced early adversity.


Assuntos
Terapia Comportamental/métodos , Intervenção Educacional Precoce , Cuidados no Lar de Adoção/psicologia , Hidrocortisona/sangue , Apego ao Objeto , Nível de Alerta/fisiologia , Pré-Escolar , Educação/métodos , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Lactente , Controle Interno-Externo , Masculino , Sistema Hipófise-Suprarrenal/fisiopatologia , Meio Social , Resultado do Tratamento
10.
J Neurosci ; 26(25): 6737-48, 2006 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-16793881

RESUMO

Rat pups must learn maternal odor to support attachment behaviors, including nursing and orientation toward the mother. Neonates have a sensitive period for rapid, robust odor learning characterized by increased ability to learn odor preferences and decreased ability to learn odor aversions. Specifically, odor-0.5 mA shock association paradoxically causes an odor preference and coincident failure of amygdala activation in pups until postnatal day 10 (P10). Because sensitive-period termination coincides with a declining "stress hyporesponsive period" when corticosterone release is attenuated, we explored the role of corticosterone in sensitive-period termination. Odor was paired with 0.5 mA shock in either sensitive-period (P8) or postsensitive-period (P12) pups while manipulating corticosterone. We then assessed preference/aversion learning and the olfactory neural circuitry underlying its acquisition. Although sensitive-period control paired odor-shock pups learned an odor preference without amygdala participation, systemic (3 mg/kg, i.p.; 24 h and 30 min before training) or intra-amygdala corticosterone (50 or 100 ng; during training) permitted precocious odor-aversion learning and evoked amygdala neural activity similar to that expressed by older pups. In postsensitive-period (P12) pups, control paired odor-shock pups showed an odor aversion and amygdala activation, whereas corticosterone-depleted (adrenalectomized) paired odor-shock pups showed odor-preference learning and activation of an odor learning circuit characteristic of the sensitive period. Intra-amygdala corticosterone receptor antagonist (0.3 ng; during training) infused into postsensitive-period (P12) paired odor-shock pups also showed odor-preference learning. These results suggest corticosterone is important in sensitive-period termination and developmental emergence of olfactory fear conditioning, acting via the amygdala as a switch between fear and attraction. Because maternal stimulation of pups modulates the pups' endogenous corticosterone, this suggests maternal care quality may alter sensitive-period duration.


Assuntos
Tonsila do Cerebelo/fisiologia , Condicionamento Clássico/fisiologia , Corticosterona/metabolismo , Rede Nervosa/fisiologia , Odorantes , Choque , Adrenalectomia/métodos , Fatores Etários , Tonsila do Cerebelo/efeitos dos fármacos , Análise de Variância , Animais , Animais Recém-Nascidos , Comportamento Animal , Condicionamento Clássico/efeitos dos fármacos , Corticosterona/farmacologia , Desoxiglucose/farmacocinética , Emoções , Feminino , Antagonistas de Hormônios/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Mifepristona/farmacologia , Rede Nervosa/efeitos dos fármacos , Radioimunoensaio/métodos , Ratos , Ratos Long-Evans
11.
Brain Res ; 1138: 1-9, 2007 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-17276416

RESUMO

Development of the hypothalamo-pituitary-adrenocortical (HPA) axis is marked by a diminution in stress responsiveness early in the postnatal period (days 4-14 in the rat). This 'stress hyporesponsive period' (SHRP) is thought to be at least in part centrally mediated. To investigate central mechanisms underlying the SHRP, this study assessed expression of glutamic acid decarboxylase (GAD) 67 in key stress-regulatory regions in the forebrain following acute stress with or without prior maternal deprivation. This isoform of GAD is known to be induced by stress in the adult and is believed to be a major contributor to production of the inhibitory neurotransmitter GABA under stimulated conditions. Expression of GAD67 mRNA was increased in the hippocampus, central amygdala and dorsomedial hypothalamus in pups tested early in the SHRP (day 6) or after its conclusion (day 18). In contrast, restraint caused a down-regulation of GAD67 mRNA in these structures when tested later in the SHRP (day 12). GAD67 mRNA expression was not affected by prior maternal deprivation in these regions. Reduced GABA production in the hippocampus (interneurons) is consistent with enhanced HPA axis inhibition, whereas reduced amygdalar expression predicts impaired stress excitation. Expression of GAD67 mRNA in the bed nucleus of the stria terminalis (BST) was minimally affected by acute restraint or maternal deprivation during the SHRP. However, older animals showed down-regulation of basal expression following maternal deprivation and substantial GAD67 mRNA up-regulation in both deprived and non-deprived groups following acute restraint. In contrast, non-responsiveness of the BST during the SHRP suggests either that BST GABA circuits are not actively engaged by stressors during this period or that circuits regulating BST GAD67 production are not yet in place. Overall, the data implicate forebrain GABA circuits in inhibition of HPA axis activity during the SHRP.


Assuntos
Glutamato Descarboxilase/genética , Hipotálamo/fisiopatologia , Isoenzimas/genética , Sistema Límbico/fisiopatologia , Prosencéfalo/fisiopatologia , RNA Mensageiro/metabolismo , Estresse Fisiológico/fisiopatologia , Ácido gama-Aminobutírico/metabolismo , Envelhecimento/metabolismo , Animais , Feminino , Hipotálamo/enzimologia , Sistema Límbico/enzimologia , Masculino , Privação Materna , Inibição Neural , Vias Neurais/fisiopatologia , Prosencéfalo/enzimologia , Prosencéfalo/metabolismo , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Restrição Física , Núcleos Septais/fisiopatologia , Estresse Fisiológico/etiologia , Estresse Fisiológico/metabolismo , Distribuição Tecidual , Regulação para Cima
12.
J Pharmacol Toxicol Methods ; 55(2): 224-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-16839786

RESUMO

Tyloxapol (Triton WR 1339) is a non-ionic detergent that inhibits lipoprotein lipase and thereby raises levels of serum lipids. It is used frequently for acute studies on lipids in rats but not for subacute or chronic studies. In the present work, we found that tyloxapol must be injected intravenously three times each week in order to have high and sustained levels of serum cholesterol and triglycerides for 1, 2, or 3 weeks. These results make it possible to extend the use of tyloxapol into chronic studies of hyperlipemia and vascular disease.


Assuntos
Modelos Animais de Doenças , Inibidores Enzimáticos/toxicidade , Hiperlipidemias/induzido quimicamente , Lipase Lipoproteica/antagonistas & inibidores , Polietilenoglicóis/toxicidade , Tensoativos/toxicidade , Animais , Colesterol/sangue , Injeções Intravenosas , Ratos , Ratos Endogâmicos Lew , Triglicerídeos/sangue
13.
Psychoneuroendocrinology ; 31(1): 59-68, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16005570

RESUMO

BACKGROUND: Autism is a severe neurodevelopmental disorder characterized by impairment in communication, social interaction, repetitive behaviors and difficulty adapting to novel experiences. The Hypothalamic-Pituitary-Adrenocortical (HPA) system responds consistently to perceived novel or unfamiliar situations and can serve as an important biomarker of the response to a variety of different stimuli. Previous research has suggested that children with autism may exhibit dysfunction of the HPA system, but it is not clear whether altered neuroendrocrine regulation or altered responsiveness underlies the differences between children with and without autism. In order to provide preliminary data concerning HPA regulation and responsiveness, we compared circadian rhythms and response to a non-social, environmental stressor in children with and without autism. METHODS: Circadian rhythms of cortisol were estimated in children with (N=12) and without (N=10) autism via analysis of salivary samples collected in the morning, afternoon and evening on 2 consecutive days. HPA responsiveness was assessed by examining the time course of changes in salivary cortisol in response to a mock MRI. RESULTS: Both groups showed expected circadian variation with higher cortisol concentration in morning than in the evening samples. The children with autism, but not typical children, showed a more variable circadian rhythm as well as statistically significant elevations in cortisol following exposure to a novel, nonsocial stimulus. CONCLUSIONS: The results suggest that children with autism process and respond idiosyncratically to novel and threatening events resulting in an exaggerated cortisol response.


Assuntos
Transtorno Autístico/metabolismo , Ritmo Circadiano/fisiologia , Hidrocortisona/metabolismo , Estresse Psicológico/metabolismo , Transtorno Autístico/psicologia , Criança , Meio Ambiente , Retroalimentação Psicológica , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Saliva/metabolismo , Sensação/fisiologia , Manejo de Espécimes , Estresse Psicológico/psicologia , Inquéritos e Questionários
14.
Brain Res ; 1121(1): 83-94, 2006 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-17055465

RESUMO

Early in life, there is a delicate and critical balance aimed to maintain low hormone responses derived from the stress responsive hypothalamic-pituitary-adrenal axis (HPA). However, in the infant rat hypothalamic corticotrophin-releasing hormone (CRH) stress responses to environmental events are clearly seen even though other elements of the HPA axis may have limited responses. In view of the role of CRH in mediating behavior associated with stress and anxiety, we considered the ontogeny and the effects of prolonged maternal deprivation (DEP) in brain areas that express CRH-related molecules outside the hypothalamus. We hypothesized that DEP would alter the ontogeny of CRH, CRH binding protein and CRH receptor 1 in prefrontal cortex, amygdala, septum and hippocampus, areas that are part of the CRH extra hypothalamic system, and that a differential modulation would be observed in response to restraint. We compared non-deprived animals to animals subjected to 24 h of DEP at 6, 12 and 18 days of life. We found (1) developmental patterns, which were idiosyncratic to the anatomical area examined, and (2) a temporal response of mRNA levels which was also site specific. The genomic changes are not always related to maternal deprivation status, in fact DEP enhanced, suppressed or had no consequence on the underlying ontogenic progression and restraint response of these CRH-related molecules. We conclude that the extra hypothalamic CRH system is a dynamic system responding to developmental and environmental demands challenging the basic assumption of stress hypo responsiveness in the infant rat. This modulation may have important repercussions on morphological organization and events leading to neuroprotection.


Assuntos
Encéfalo/fisiologia , Hormônio Liberador da Corticotropina/genética , Privação Materna , Receptores de Hormônio Liberador da Corticotropina/genética , Envelhecimento , Tonsila do Cerebelo/crescimento & desenvolvimento , Tonsila do Cerebelo/fisiologia , Animais , Encéfalo/crescimento & desenvolvimento , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiologia , Hibridização In Situ , Masculino , Modelos Animais , RNA Mensageiro , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Estresse Psicológico
15.
Artigo em Inglês | MEDLINE | ID: mdl-16239056

RESUMO

Lithium treatment of patients and laboratory animals causes increased body weight. Lithium also elevates the plasma corticosterone levels of rats. Our purpose was to correlate the gain of body weight with the effects of lithium on the thymus gland, the organ most susceptible to stress and to elevated corticosterone levels. Toward this end, it was also necessary to establish a reliable and reproducible model by use of an inbred strain of rats. Female rats of the inbred Lewis strain were injected subcutaneously with lithium chloride or saline for an 18-day period. Necropsies were performed one day after the last treatment or at intervals during the treatment period. Lithium increased body weight gain compared to controls in all the experiments on Lewis rats. Contrary to the body as a whole, lithium caused loss of weight of the thymus gland. The spleen lost less weight than the thymus. Both lithium and nonspecific stress elevate plasma corticosterone and cause thymolysis. Mild nonspecific stress is known to cause increased weight gain in rats as well as in humans. Our data suggest that lithium acts like nonspecific stress to increase weight gain as a consequence of elevated glucocorticoids, manifested in our experiments by thymolysis. This mechanism has not been proposed previously.


Assuntos
Antimaníacos/farmacologia , Peso Corporal/efeitos dos fármacos , Cloreto de Lítio/farmacologia , Timo/efeitos dos fármacos , Animais , Corticosterona/sangue , Feminino , Ratos , Ratos Endogâmicos Lew
16.
Child Maltreat ; 11(2): 189-97, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16595852

RESUMO

Young children in foster care have often experienced inadequate early care and separations from caregivers. Preclinical studies suggest that early inadequate care and separations are associated with long-term changes in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the daytime pattern of cortisol production was examined among 55 young children who had been placed into foster care and 104 children who had not. Saliva samples were taken at wake-up, in the afternoon, and bedtime for 2 days. Average salivary cortisol values for each time of day were computed. A group (foster vs. comparison) time (morning, afternoon, night) interaction emerged, reflecting less decline in levels across the day for foster than comparison children. Daytime patterns were categorized as typical, low, or high. Children who had been in foster care had higher incidences of atypical patterns of cortisol production than children who had not. These differences suggest that conditions associated with foster care interfere with children's ability to regulate neuroendocrine functioning.


Assuntos
Ritmo Circadiano/fisiologia , Cuidados no Lar de Adoção/psicologia , Hidrocortisona/metabolismo , Cuidadores , Desenvolvimento Infantil , Pré-Escolar , Feminino , Humanos , Hidrocortisona/análise , Sistema Hipotálamo-Hipofisário , Lactente , Masculino , Sistema Hipófise-Suprarrenal , Saliva/química
17.
Psychoneuroendocrinology ; 30(10): 939-46, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15958281

RESUMO

The purpose of this paper is two fold. First, to revisit the issue of the definition of stress and to highlight the difficulties with the contemporary definitions and, second, to review the literature on the influence of early experiences on the endocrine stress responses and behavior in rodents, sub-human primates and humans. Early experiences, usually involving some manipulation that results in disruption of the mother-infant relationship, have been shown to have long-term influences on the behavioral and endocrine responses to stress. In the rodent, brief periods of separation result in an attenuated adrenal response to stress (reduced secretion of corticosterone). In contrast, longer periods of separation result in an exaggerated response and several behavioral anomalies i.e. increased alcohol consumption, increased startle response etc. However, the effects of disruptions of the mother-infant relationships in primates reveal a pattern of behavioral disturbance but little influence on the endocrine response. Brief maternal separations result in a blunted cortisol response in juvenile squirrel monkeys. The long-term effects of early experiences in humans are very difficult to interpret. It is not possible to determine the length and severity of the experiences, and when in development the experiences were imposed on the child. Despite these limitations, there is a general consensus that adverse early experiences contribute to adult psychopathology.


Assuntos
Envelhecimento/psicologia , Estresse Psicológico/fisiopatologia , Adulto , Animais , Criança , Abuso Sexual na Infância , Feminino , Humanos , Individualidade , Masculino , Privação Materna , Primatas
18.
Brain Res Dev Brain Res ; 158(1-2): 92-6, 2005 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-16026857

RESUMO

Maternal care in the rabbit is restricted to a single 3- to 5-min period of nursing each day. One to three hours prior to the arrival of the mother, pups exhibit anticipatory behavioral arousal and elevation of core body temperature. In rodents, the hypothalamic-pituitary-adrenal axis is quiescent and levels of the adrenal hormone, corticosterone (CORT), are stable and extremely low during the first days of life, which are known collectively as the stress-hyporesponsive period (SHRP). It has been proposed that the rabbit also has an SHRP. However, we decided to examine CORT changes associated with the daily nursing bout, since behavioral arousal, core body temperature, and CORT are elevated prior to the onset of feeding in many other species. We scheduled the nursing bout at 1000 h and analyzed CORT concentration using RIA in pups sampled at various intervals after suckling. CORT levels showed a circadian variation that peaked at the time of the daily nursing bout. After nursing, values steadily decreased to a nadir at 2200 h and then rose again in advance of the next scheduled nursing. The three-fold difference between the highest (1000 h) and the lowest (2200 h) CORT values suggests that either the SHRP does not exist in rabbit pups or else it has properties that differ from those described for rodents. Unlike rodents, rabbit pups show a circadian secretion of CORT synchronized to the scheduled nursing bout.


Assuntos
Animais Recém-Nascidos/fisiologia , Ritmo Circadiano/fisiologia , Corticosterona/metabolismo , Fatores Etários , Análise de Variância , Animais , Nível de Alerta/fisiologia , Comportamento Animal , Temperatura Corporal/fisiologia , Comportamento Alimentar , Feminino , Masculino , Privação Materna , Gravidez , Coelhos , Radioimunoensaio/métodos , Distribuição Aleatória , Fatores de Tempo
19.
Neurosci Biobehav Rev ; 27(1-2): 83-9, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12732225

RESUMO

Long-term effects of early experiences have been well documented in rodents, non-human primates and humans. The influence of early experiences on the regulation of the hypothalamic-pituitary-adrenal has demonstrated that this biological system is highly plastic and is permanently modified by early experiences. The effects of brief periods of maternal separation in rodents tend to result in a reduction of the stress response, whereas longer periods of maternal separation produce an animal that is hyperresponsive. The effect of disruptions of mother-infant interactions on the HPA axis in non-human primates has not been clearly established. However, the primate research has primarily focused on more permanent separation paradigms and thus it is difficult to compare the rodent studies with those conducted in primates. The present study attempted to use a separation procedure in monkeys that more closely resembled the rodent model. Intermittent separation during infancy followed by reunion with the mother were shown to lead to a significant reduction in both the cortisol response and the response of the noradrenergic system following social isolation in juvenile squirrel monkeys at 2 and 3 years of age. The behavioral response (vocalizations) was also reduced.


Assuntos
Dependência Psicológica , Privação Materna , Vocalização Animal/fisiologia , Animais , Animais Recém-Nascidos , Comportamento Animal , Análise Química do Sangue/métodos , Feminino , Ácido Homovanílico/líquido cefalorraquidiano , Hidrocortisona/sangue , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Macaca mulatta , Masculino , Metoxi-Hidroxifenilglicol/líquido cefalorraquidiano
20.
Endocrinology ; 143(5): 1717-25, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11956153

RESUMO

Rats exhibit a stress hyporesponsive period from postnatal day (PND) 4-14 in which the neonate displays a minimal corticosterone response to stress. We used the maternal deprivation model to test whether this adrenocortical hyporesponsiveness to stress results from a decrease in adrenal sensitivity to ACTH. Neonates (PND 6, 9, and 12) were injected ip with dexamethasone to block endogenous ACTH release, and 4 h later injected with graded doses of ACTH and killed. In another experiment, neonates were injected with isotonic saline and adrenal glands were collected at 30, 60, and 120 min post injection to examine c-fos and tyrosine hydroxylase mRNA levels using in situ hybridization. Maternally deprived pups demonstrated elevated corticosterone levels at the two highest ACTH doses and showed a greater magnitude in glucocorticoid secretion compared with the nondeprived pups. Maternally deprived pups given a saline injection exhibited elevated basal and stress-induced levels of corticosterone, in contrast to the nondeprived pups that showed a minimal response. Strikingly, maternally deprived pups exhibited elevated levels of adrenocortical c-fos mRNA, whereas the nondeprived pups did not. In contrast, the pattern of c-fos gene expression in the adrenal medulla in both groups did not display any correlation with glucocorticoid secretion. Tyrosine hydroxylase gene expression in the adrenal medulla was observed in both nondeprived and maternally deprived pups, with the latter exhibiting an earlier response of greater magnitude. These results demonstrate that the suppression of steroidogenesis occurs directly in the adrenal cortex and provide further evidence for an adrenal hyporesponsive period in the rat.


Assuntos
Glândulas Suprarrenais/crescimento & desenvolvimento , Glândulas Suprarrenais/metabolismo , Animais Recém-Nascidos/fisiologia , Genes fos/genética , RNA Mensageiro/biossíntese , Tirosina 3-Mono-Oxigenase/biossíntese , Hormônio Adrenocorticotrópico/farmacologia , Animais , Corticosterona/sangue , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/farmacologia , Processamento de Imagem Assistida por Computador , Hibridização In Situ , Masculino , Privação Materna , Sondas RNA , RNA Mensageiro/genética , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/genética
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