Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biol Psychiatry ; 86(7): 545-556, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31443932

RESUMO

BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31302732

RESUMO

Preclinical studies indicate a link between the kynurenine pathway and monocyte chemoattractant protein-1 (MCP-1), but there is a lack of clinical studies examining this further. We here perform a secondary analysis of kynurenine metabolites and MCP-1 in cerebrospinal fluid of 23 twins affected from schizophrenia, bipolar disorder or unaffected. We show an association between MCP-1 and kynurenic acid (KYNA), driven by unique environmental influences and a less pronounced association between MCP-1 and tryptophan. No association was detected between MCP-1 and quinolinic acid. Further studies on the mechanism behind the putative relationship between KYNA and MCP-1 are needed.

3.
Psychiatry Res ; 278: 180-187, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31207455

RESUMO

Twin- and family studies have shown variations in the heritability estimates of bipolar disorder (BPD). The current study uses an updated statistical methodology for heritability estimation in BPD by taking available time of follow-up into account while controlling for co-variates. We identified monozygotic and dizygotic same and different sex twins with BPD (n = 804) or unaffected from BPD (n = 91,604) from the Swedish Twin Register and the National Patient Register. We applied structural equational modeling with inversed probability weighting to estimate the heritability, taking into account censoring and truncation of data. Sex-limitation models were constructed to analyze qualitative or quantitative sex-differences in BPD. Heritability for BPD was 60.4% (95% Confidence Interval: 50.3-70.5) after age, sex, left-hand truncation and censoring of the data was taken into account. A larger proportion of females were affected from BPD (females 62.2%; males 37.8%, p < 0.001), but no sex-difference in BPD heritability was found, nor any sex-specific genetic effects. We demonstrated a robust 60% heritability for BPD with no evidence of sex-specific genetic effects on disease liability.

4.
Schizophr Res ; 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30121189

RESUMO

The schizophrenia and bipolar twin study in Sweden (STAR) is a large nation-wide cohort of monozygotic (MZ) and dizygotic (DZ) same-sex twins with schizophrenia or bipolar disorder and healthy control pairs, extensively characterized with brain imaging, neuropsychological tests, biomarkers, genetic testing, psychiatric symptoms and personality traits. The purpose is to investigate genetic and environmental mechanisms that give rise to schizophrenia and bipolar disorder as well as the intermediate phenotypes. This article describes the design, recruitment, data collection, measures, collected twins' characteristics, diagnostic procedures as well as ongoing and planned analyses. Identification of biomarkers, genetic and epigenetic variation and the development of specific and common endophenotypes for schizophrenia and bipolar disorder are potential gains from this cohort.

5.
J Atten Disord ; : 1087054718787034, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30024318

RESUMO

OBJECTIVE: The Quantified Behavioral Test (QbTest) is a computerized diagnostic test for ADHD, used in clinical psychiatric care, but its validity may be questioned. We analyzed the QbTest's diagnostic validity and its relation to cognitive ability and psychosocial factors in an adolescent population with a high occurrence of neurodevelopmental disorders. METHOD: In total, 340 participants aged 15 years, completed the QbTest, along with questionnaires, clinical and intelligence quotient (IQ) assessments. RESULTS: The clinical assessment resulted in 89 (26%) participants with ADHD. Area under curve (AUC) scores indicated a random to poor validity of the QbTest (AUC range = 0.48-0.64). QbTest scores of inattention and impulsivity correlated with IQ. CONCLUSION: The QbTest was insufficient as a diagnostic test for ADHD, and was not able to differentiate ADHD from other neurodevelopmental conditions. Clinicians should be aware of the dubious discriminating power of the QbTest.

6.
Psychiatry Res ; 258: 9-14, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28968513

RESUMO

Previous studies on the relationship between autoimmune diseases, schizophrenia, and bipolar disorder are mainly based on hospital discharge registers with insufficient coverage of outpatient data. Furthermore, data is scant on the prevalence of autoimmune diseases in bipolar subgroups. Here we estimate the self-reported prevalences of autoimmune diseases in schizophrenia, bipolar disorder type I and II, and controls. Lifetime prevalence of autoimmune diseases was assessed through a structured interview in a sample of 9076 patients (schizophrenia N = 5278, bipolar disorder type I N = 1952, type II N = 1846) and 6485 controls. Comparative analyses were performed using logistic regressions. The prevalence of diabetes type 1 did not differ between groups. Hyperthyroidism, hypothyroidism regardless of lithium effects, rheumatoid arthritis, and polymyalgia rheumatica were most common in bipolar disorder. Systemic lupus erythematosus was less common in bipolar disorder than in the other groups. The rate of autoimmune diseases did not differ significantly between bipolar subgroups. We conclude that prevalences of autoimmune diseases show clear differences between schizophrenia and bipolar disorder, but not between the bipolar subgroups.


Assuntos
Doenças Autoimunes/epidemiologia , Transtorno Bipolar/epidemiologia , Esquizofrenia/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
7.
Eur Arch Psychiatry Clin Neurosci ; 267(5): 391-402, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28039552

RESUMO

Schizophrenia and bipolar disorder are debilitating psychiatric disorders with partially shared symptomatology including psychotic symptoms and cognitive impairment. Aberrant levels of microglia and neurodegenerative cerebrospinal fluid (CSF) markers have previously been found in schizophrenia and bipolar disorder. We aimed to analyze familial and environmental influences on these CSF markers and their relation to psychiatric symptoms and cognitive ability. CSF was collected from 17 complete twin pairs, nine monozygotic and eight dizygotic, and from one twin sibling. Two pairs were concordant for schizophrenia, and 11 pairs discordant for schizophrenia, schizoaffective disorder or bipolar disorder, and four pairs were not affected by psychotic disorders. Markers of microglia activation [monocyte chemoattractant protein-1 (MCP-1), chitinase 3-like protein 1 (YKL-40), and soluble cluster of differentiation 14 (sCD14)], markers of ß-amyloid metabolism (AßX-38, AßX-40, AßX-42 and Aß1-42), soluble amyloid precursor proteins (sAPP-α and sAPP-ß), total tau (T-tau), phosphorylated tau (P-tau), and CSF/serum albumin ratio were measured in CSF using immunoassays. Heritability of the CSF markers was estimated, and associations to psychiatric and cognitive measurements were analyzed. Heritability estimates of the microglia markers were moderate, whereas several neurodegenerative markers showed high heritability. In contrast, AßX-42, Aß1-42, P-tau and CSF/serum albumin ratio were influenced by dominant genetic variation. Higher sCD14 levels were found in twins with schizophrenia or bipolar disorder compared to their not affected co-twins, and higher sCD14-levels were associated with psychotic symptoms. The study provides support for a significant role of sCD14 in psychotic disorders and a possible role of microglia activation in psychosis.


Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Doenças em Gêmeos , Receptores de Lipopolissacarídeos/metabolismo , Transtornos Psicóticos/líquido cefalorraquidiano , Adulto , Peptídeos beta-Amiloides/sangue , Biomarcadores/sangue , Quimiocina CCL2/sangue , Quimiocina CCL2/líquido cefalorraquidiano , Proteína 1 Semelhante à Quitinase-3/sangue , Proteína 1 Semelhante à Quitinase-3/líquido cefalorraquidiano , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Transtornos Psicóticos/sangue , Transtornos Psicóticos/genética , Transtornos Psicóticos/psicologia , Estatística como Assunto , Gêmeos Dizigóticos , Gêmeos Monozigóticos
8.
Psychiatry Res ; 247: 105-112, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27886578

RESUMO

Increased cytokines and kynurenic acid (KYNA) levels in cerebrospinal fluid (CSF) have been reported in patients with schizophrenia and bipolar disorder. The aim of the present study was to investigate cytokines and kynurenines in the CSF of twin pairs discordant for schizophrenia or bipolar disorder and to study these CSF markers in relation to psychotic symptoms and personality traits. CSF levels of tryptophan (TRP), KYNA, quinolinic acid (QUIN), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-α) were analyzed in 23 twins with schizophrenia or bipolar disorder, and in their not affected co-twins. Ratings of psychotic symptoms and personality traits were made using the Scales for Assessment of Negative and Positive symptoms, the Structured Clinical Interview for DSM-IV - Axis II Disorders, and the Schizotypal Personality Questionnaire - Brief. A total score for psychotic symptoms and personality traits was constructed for analysis. CSF KYNA was associated with the score for psychotic symptom and personality traits. TNF-α and IL-8 were associated, and the intra-pair differences scores of TNF-α and IL-8 were highly correlated. Intraclass correlations indicated genetic influences on CSF KYNA, TRP, IL-8 and TNF-α. The association between KYNA and psychotic symptoms further supports a role of KYNA in psychotic disorders.


Assuntos
Transtorno Bipolar/líquido cefalorraquidiano , Ácido Cinurênico/líquido cefalorraquidiano , Personalidade , Esquizofrenia/líquido cefalorraquidiano , Psicologia do Esquizofrênico , Gêmeos/psicologia , Transtorno Bipolar/psicologia , Feminino , Humanos , Interleucina-6/líquido cefalorraquidiano , Interleucina-8/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/complicações , Ácido Quinolínico/líquido cefalorraquidiano , Triptofano/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano
9.
Fertil Steril ; 105(6): 1594-1602.e3, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26920258

RESUMO

OBJECTIVE: To investigate associations between depression, anxiety, and antidepressants before in vitro fertilization (IVF) and IVF cycle outcomes, including pregnancy, live birth, and miscarriage. DESIGN: Nationwide register-based cohort study. SETTING: Not applicable. PATIENT(S): Nulliparous women undergoing their first IVF cycle recorded in the Swedish Quality Register of Assisted Reproduction, January 2007 to December 2012 (n = 23,557). INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Associations between diagnoses of depression/anxiety, antidepressants, and IVF cycle outcome evaluated using logistic regression to produce adjusted odds ratios (AOR) and 95% confidence intervals (CI). RESULT(S): In total, 4.4% of women had been diagnosed with depression/anxiety and/or dispensed antidepressants before their IVF first cycle. The odds for pregnancy and live birth were decreased (n = 1,044; AOR = 0.86; 95% CI, 0.75-0.98; and AOR = 0.83; 95% CI, 0.72-0.96, respectively). For women with a prescription for a selective serotonin reuptake inhibitor (SSRI) only (n = 829), no statistically significant associations were found. Women with non-SSRI antidepressants (n = 52) were at reduced odds of pregnancy (AOR = 0.41; 95% CI, 0.21-0.80) and live birth (AOR = 0.27; 95% CI, 0.11-0.68). Women with a depression/anxiety diagnosis with no antidepressant (n = 164) also had reduced odds of pregnancy (AOR = 0.58; 95% CI, 0.41-0.82) and live birth (AOR = 0.60; 95% CI, 0.41-0.89). Among the women who became pregnant (39.7%), there were no statistically significant associations between exposure and miscarriage except for the women taking non-SSRI antidepressants (AOR = 3.56; 95% CI, 1.06-11.9). CONCLUSION(S): A diagnosis of depression/anxiety and/or treatment with antidepressants before IVF was associated with slightly reduced odds of pregnancy and live birth. Women with the presence of depression/anxiety without antidepressants had a more pronounced reduction in odds, implying that the underlying disorder is important for the observed association.


Assuntos
Antidepressivos/uso terapêutico , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Fertilização In Vitro/métodos , Taxa de Gravidez , Adolescente , Adulto , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Estudos de Coortes , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Fertilização In Vitro/tendências , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Gravidez , Taxa de Gravidez/tendências , Sistema de Registros , Suécia/epidemiologia , Resultado do Tratamento , Adulto Jovem
10.
Mult Scler ; 20(14): 1881-91, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25013151

RESUMO

BACKGROUND: Psychiatric disorders are known to be prevalent in multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to study comorbidity between MS and bipolar disorder, schizophrenia and depression in a nationwide cohort and to determine whether shared genetic liability underlies the putative association. METHODS: We identified ICD-diagnosed patients with MS (n = 16,467), bipolar disorder (n = 30,761), schizophrenia (n = 22,781) and depression (n = 172,479) in the Swedish National Patient Register and identified their siblings in the Multi-Generation Register. The risk of MS was compared in psychiatric patients and in matched unexposed individuals. Shared familial risk between MS and psychiatric disorders was estimated by sibling comparison. RESULTS: The risk of MS was increased in patients with bipolar disorder (hazard ratio (HR) 1.8, 95% confidence interval (CI) 1.6-2.2, p < 0.0001) and depression (HR 1.9, 95% CI 1.7-2.0, p < 0.0001). MS risk in schizophrenia was decreased (HR 0.6, 95% CI 0.4-0.9, p = 0.005). The association between having a sibling with a psychiatric disorder and developing MS was not significant. CONCLUSION: We found a strong positive association between MS and bipolar disorder and depression that could not be explained by genetic liability. The unexpected negative association between MS and schizophrenia might be spurious or indicate possible protective mechanisms that warrant further exploration.


Assuntos
Transtorno Bipolar/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Esclerose Múltipla/epidemiologia , Esquizofrenia/epidemiologia , Irmãos , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Comorbidade , Transtorno Depressivo/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Suécia/epidemiologia
11.
Schizophr Res ; 143(1): 192-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23182441

RESUMO

Schizophrenia is a diagnosis with a set of symptoms of aberrant psychological phenomena. Here, we discuss that there may be an imbalance of proteostasis of neurons in the brain leading to increase in membrane shedding and buildup of microparticles (MPs) appearing in the cerebrospinal fluid. The number of MPs can be determined and their phenotypes verified by size and membrane expression with flow cytometry. This is the first report of specified MPs in cerebrospinal fluid (CSF) in schizophrenia. Two 56-year-old Swedish-born female monozygotic twins of Caucasian ethnicity with onset of schizophrenia more than 30years ago were studied. Three fractions of fresh CSF were examined for microparticles by flow cytometry analysis, which measure the specific binding of antibodies to CD42a (platelet-MP; 33 GPIX), CD144 (endothelial-MP; Ve-cadherin), CD45 (leukocyte-MP; pan-leukocyte antigen) and of phosphatidylserine to lactadherin. The patients with schizophrenia displayed more phosphatidylserine-positive MPs in CSF compared with healthy control subjects. The scanning electron microscopic (SEM) structures in CSF studied over a 3-year period in twins with schizophrenia were of similar appearance at both time points. The increased number of MPs in fresh CSF may be a sign of enhanced membrane shedding in the central nervous system. Such MPs can be investigated for both human and non-human DNA, RNA and microRNA that may activate different immune signaling systems in patients with schizophrenia.


Assuntos
Micropartículas Derivadas de Células/fisiologia , Esquizofrenia/líquido cefalorraquidiano , Antígenos CD/líquido cefalorraquidiano , Plaquetas/metabolismo , Plaquetas/ultraestrutura , Micropartículas Derivadas de Células/ultraestrutura , Feminino , Citometria de Fluxo , Humanos , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Fagócitos/patologia , Fagócitos/ultraestrutura , Esquizofrenia/sangue , Gêmeos Monozigóticos
12.
PLoS One ; 7(9): e45994, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23049916

RESUMO

BACKGROUND: Using scanning electron microscopy, microscopic structures have been identified in fresh cerebrospinal fluid (CSF) in patients with schizophrenia and bipolar disorder, but only rarely in control subjects. However, it has not been determined whether these microscopic particles represent state or trait markers, i.e. if their presence is related to clinical manifestations of the disease or if they also can be found in as yet asymptomatic individuals with a genetic liability. This question can be addressed by studying twins discordant or concordant for schizophrenia or bipolar disorder. METHODOLOGY/PRINCIPAL FINDINGS: We investigated microscopic structures in CSF in 102 individuals: 21 monozygotic and 16 dizygotic twins affected or not affected with schizophrenia, schizoaffective disorder or bipolar disorder and in 65 healthy singleton controls. A first and a second fraction of CSF was freshly applied on filters and examined by scanning electron microscopy technique. Spherical particles with lipid appearance averaging between 0.1 to 8.0 µm in diameter were detected in the center of the filter as well as located in the margins of larger aggregates binding in a viscous state. Structures were found in 12 of 17 probands, 5 of 12 healthy co-twins and 3 of 73 healthy controls. Thus, a positive microscopic finding significantly increased the likelihood of belonging to the proband group (OR=48, 95% CL: 8.2-550, p<0.0001) and the co-twin-group (OR=16, 95% CL: 2.0-218, p=0.006). Age, sex, history of alcohol abuse or anxiety syndrome, somatic disorder and markers of acute inflammatory activity did not account for group differences; nor did exposure to psychotropic medication. CONCLUSION: Presence of microscopic particles in CSF may possibly reflect trait dependent genetic or environmental vulnerability in patients with schizophrenia, schizoaffective disorder or bipolar disorder.


Assuntos
Transtorno Bipolar/líquido cefalorraquidiano , Esquizofrenia/líquido cefalorraquidiano , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Doenças em Gêmeos , Feminino , Humanos , Masculino , Microscopia Eletrônica de Varredura/métodos , Pessoa de Meia-Idade , Modelos Neurológicos , Razão de Chances , Cimento de Policarboxilato/química , Análise de Regressão , Suécia , Gêmeos Dizigóticos , Gêmeos Monozigóticos
13.
J Exp Biol ; 214(Pt 6): 907-14, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21346117

RESUMO

Corticotropin-releasing factor (CRF) is central in the stress response but also modulates several behaviors including anxiety-related behaviors and aggression. In this study, juvenile rainbow trout (Oncorhynchus mykiss) were tested for competitive ability, determined during dyadic fights for dominance, after intracerebroventricular (i.c.v.) administration of CRF, urotensin I (UI), the non-specific CRF antagonist α-helical RF(9-41) (ahCRF) or the CRF receptor subtype 1-specific antagonist antalarmin, when paired with a mass-matched con-specific injected with saline. In addition, isolated fish received the same substances. Plasma cortisol and brain monoamines were monitored in all fish. Most fish receiving CRF showed a conspicuous behavior consisting of flaring the opercula, opening the mouth and violent shaking of the head from side to side. When this occurred, the fish immediately forfeited the fight. Similar behavior was observed in most fish receiving UI but no effect on outcome of dyadic fights was noted. This behavior seems similar to non-ambulatory motor activity seen in rats and could be anxiety related. Furthermore, fish receiving CRF at a dose of 1000 ng became subordinate, whereas all other treatments had no effects on the outcome of dyadic fights. In addition, isolated fish receiving ahCRF had lower brain stem concentrations of 5-hydroxyindoleacetic acid, serotonin, 3,4-dihydroxyphenylacetic acid and dopamine. In conclusion, CRF seems to attenuate competitive ability, and both CRF and UI seem to induce anxiety-like behavior.


Assuntos
Agressão/fisiologia , Ansiedade/metabolismo , Comportamento Animal , Hormônio Liberador da Corticotropina/metabolismo , Oncorhynchus mykiss/fisiologia , Urotensinas/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Agressão/efeitos dos fármacos , Animais , Ansiedade/sangue , Comportamento Animal/efeitos dos fármacos , Hormônio Liberador da Corticotropina/antagonistas & inibidores , Hormônio Liberador da Corticotropina/farmacologia , Dopamina/metabolismo , Hidrocortisona/sangue , Ácido Hidroxi-Indolacético/metabolismo , Oncorhynchus mykiss/sangue , Fragmentos de Peptídeos/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Ratos , Serotonina/metabolismo , Predomínio Social
14.
Adv Exp Med Biol ; 617: 573-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18497084

RESUMO

Prostate cancer (PC) is one of the most common cancers among men, and vitamin D and its metabolites are candidates for prevention and therapy of this disease. The vitamin D metabolites, 1, 25-dihydroxyvitamin D3 (1,25D) and 25-hydroxyvitamin D3, decreases cellular proliferation and invasiveness, and stimulates differentiation of PC cells. However, the underlying mechanisms are not fully clarified, and there is evidence that some of these effects of the vitamin D system are mediated by specific membrane-associated receptors/binding proteins in addition to its nuclear receptor, suggesting multiple regulatory pathways. The aim of the present study was to examine the role of membrane initiated pathways mediating effects of 1,25D on cell invasiveness in LNCaP cells. Treatment with 1,25D evoked a dose-dependent activation of the JNK/SAPK MAPK signaling pathways within 10 min, demonstrating membrane initiated signaling of 1,25D in LNCaP cells. Furthermore, treatment with 1,25D decreased LNCaP cell invasiveness by approximately 20% after 48 h. Using an inhibitor (SP600125) for the JNK/SAPK MAPK signaling pathway in combination with 1,25D on LNCaP cells, the inhibitory action of 1,25D on invasiveness was eliminated. In conclusion, 1,25D decrease invasiveness of LNCaP cells by interaction with a putative membrane associated receptor, which activate membrane, initiated signaling via the JNK/SAPK MAPK signaling pathway.


Assuntos
Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vitamina D/análogos & derivados , Antracenos/farmacologia , Proliferação de Células/efeitos dos fármacos , Quimioterapia Combinada , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Masculino , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Invasividade Neoplásica , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/patologia , Neoplasias da Próstata/patologia , Células Tumorais Cultivadas , Vitamina D/farmacologia
15.
Gen Comp Endocrinol ; 141(1): 58-65, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15707603

RESUMO

The effects of GH on various types of behaviour in fish are well documented although the underlying mechanisms are not fully understood. In rainbow trout, an involvement of the brain dopaminergic system in mediating the behavioural effects of GH has been indicated, as GH can alter the brain dopaminergic activity. To further examine the role of the dopaminergic system in the mediation of GH effects on locomotion and foraging, GH- and sham-implanted juvenile rainbow trout were injected with the selective D1 dopamine antagonist SCH23390 or vehicle. Swimming and feeding activity was then studied by direct observation. Brains were thereafter sampled and analysed for the content of serotonin, dopamine and their metabolites in the hypothalamus, optic tectum, cerebellum, telencephalon, and brain stem. GH increased swimming activity as well as feed intake, effects which were abolished by SCH23390. By itself, the antagonist did not affect behaviour, nor did it affect the brain monoamines. In contrast, treatment with GH, with or without SCH23390, decreased the content of the dopamine metabolite homovanillic acid (HVA) in the optic tectum and the cerebellum, as well as the serotonin content (5-HT) in the optic tectum. It is concluded that the D1 dopamine receptor of the dopaminergic system appears to be of importance in the mediation of the effects of GH on behaviour.


Assuntos
Benzazepinas/farmacologia , Comportamento Alimentar/fisiologia , Hormônio do Crescimento/farmacologia , Oncorhynchus mykiss/fisiologia , Natação/fisiologia , Animais , Encéfalo/fisiologia , Receptores de Dopamina D1/antagonistas & inibidores
16.
Horm Behav ; 46(4): 436-43, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15465529

RESUMO

There is increasing evidence that growth hormone (GH) has important behavioral effects in fish, but the underlying mechanisms are not well understood. To investigate if peripherally administered GH influences the monoaminergic activity of the brain, and how this is correlated to behavior, juvenile rainbow trout were implanted intraperitoneally with ovine GH. Fish were either kept isolated or in groups of five. The physical activity and food intake of the isolated fish were observed after 1 and 7 days, when brains were also sampled. The content of serotonin, dopamine, and noradrenaline and their metabolites in hypothalamus, telencephalon, optic tectum, and brain stem was then analyzed. For fish kept isolated for 7 days following implant, GH increased swimming activity and the levels of the dopamine metabolite 3, 4-hydroxy-phenylacetic acid (DOPAC) were higher in all brain parts examined. In the optic tectum, the levels of the dopamine metabolite homovanillic acid (HVA) were lowered by the GH treatment. One-day GH implant did not affect behavior or monoamine levels of isolated fish. In the fish kept in groups, a 7-day GH implant increased the hypothalamic levels of DOPAC, but not in the other brain parts examined, which may indicate an effect on the brain dopaminergic system from social interactions. It can be concluded that peripherally administered GH may function as a neuromodulator, affecting the dopaminergic activity of the rainbow trout brain, and this is associated with increased swimming activity.


Assuntos
Encéfalo/metabolismo , Dopamina/metabolismo , Hormônio do Crescimento/fisiologia , Movimento/fisiologia , Oncorhynchus mykiss/fisiologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Implantes Absorvíveis , Animais , Comportamento Alimentar/fisiologia , Hormônio do Crescimento/administração & dosagem , Infusões Parenterais , Norepinefrina/metabolismo , Distribuição Aleatória , Serotonina/metabolismo , Natação/fisiologia , Fatores de Tempo
17.
Horm Behav ; 43(3): 367-74, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12695109

RESUMO

Growth hormone (GH) has been demonstrated to alter the behavior of juvenile salmonids. However, the mechanisms behind this action are not yet understood. In mammals and birds, peripheral GH treatment has been shown to affect monoaminergic activity in the central nervous system, which may be a mechanism whereby GH alters behavior. To investigate if GH may influence behavior directly at the central nervous system, juvenile rainbow trout were injected with GH into the third ventricle of the brain, whereupon physical activity and food intake were observed during 2 h. Thereafter, brains were sampled and the content of serotonin, dopamine, and noradrenaline and their metabolites were measured in hypothalamus, telencephalon, optic tectum, and brainstem. The GH-treated fish increased their swimming activity relative to sham-injected controls, while appetite remained unchanged, compared with sham-injected controls. Analysis of brain content of monoamines revealed that the GH treatment caused a decrease in the dopamine metabolite homovanillic acid in the hypothalamus, indicating a lowered dopaminergic activity. It is concluded that GH may alter behavior by acting directly on the central nervous system in juvenile rainbow trout. Furthermore, GH seems to alter the dopaminergic activity in the hypothalamus. Whether this is a mechanism whereby GH affects swimming activity remains to be clarified.


Assuntos
Monoaminas Biogênicas/metabolismo , Química Encefálica/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Oncorhynchus mykiss/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Dopamina/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Hormônio do Crescimento/administração & dosagem , Injeções Intraventriculares , Atividade Motora/efeitos dos fármacos , Norepinefrina/metabolismo , Serotonina/metabolismo , Natação/psicologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA