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1.
Nervenarzt ; 91(5): 422-432, 2020 May.
Artigo em Alemão | MEDLINE | ID: mdl-32221633

RESUMO

BACKGROUND: Terrorism belongs to the extreme forms of violence that have so far received little attention in psychiatric research and are rarely mentioned in textbooks of psychiatry. After terror attacks, however, the question regularly arises whether terrorists suffer from mental disorders. OBJECTIVE AND METHODS: The aim of this review is to summarize the multidimensional causes of terrorism with special emphasis on psychopathological aspects of the perpetrators. In addition to a brief summary of the historical background and recent developments in terrorism, a literature search was performed using PubMed, SCOPUS, PsychInfo and PsychARTICLES. RESULTS: From a psychiatric point of view, a differentiation between lone terrorists and group terrorists is essential. Lone terrorists have a much higher prevalence of psychiatric disorders, such as psychotic, paranoid and affective symptoms. The majority of terrorists acting in groups rarely suffer from such mental disorders. For these perpetrators biographic aspects and socialization, group dynamics and ideological personality profiles with narcissistic, histrionic, fanatic and antisocial components are more relevant. The phenomenon of terrorism predominantly being a male domain is discussed. CONCLUSION: The manifold manifestations of terrorism are caused by complex patterns of interacting biographic, sociological, ideological and psychopathological components that differ between lone acting and group terrorists. The real causes for acts of terrorism are not various ideologies permitting violence but consist more of a pre-existing violence-oriented mentality of the perpetrators looking for such ideologies to justify their acts. The possibilities of psychiatry in prevention and early recognition are limited. Some recently developed scales for risk assessment of extreme violence are mentioned.


Assuntos
Transtornos Mentais , Terrorismo , Humanos , Masculino , Transtornos Mentais/complicações , Fatores Sexuais , Terrorismo/psicologia , Terrorismo/estatística & dados numéricos , Violência/psicologia
2.
Pharmacopsychiatry ; 49(5): 199-203, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27101233

RESUMO

Introduction: Despite the fact, that symptom-triggered alcohol withdrawal treatment is recommended by German guidelines on alcoholism, many hospitals continue to use fixed-schedule protocols, as they have been successfully applied for many years. Methods: This retrospective study compared all patients' records of alcohol withdrawal treatment from October 2010 to November 2011 at Magdeburg's University Department of Psychiatry (n=120). A symptom-triggered protocol with clomethiazole (AESB, n=46) was used in parallel with the existing fixed-schedule protocol with diazepam (n=74). Results: The symptom-triggered group showed less need of pharmacological treatment duration (p<0.001) and cumulative dosage of medication compared to the fixed-schedule protocol (p<0.006). No difference was observed regarding the need of clonidine or haloperidol (to treat blood pressure derailment or delirium) and the incidence of epileptic seizures. Discussion: Based on the shorter treatment duration and a similar rate of complications our department has switched to the symptom-triggered protocol to improve the quality of patient care.


Assuntos
Transtornos Induzidos por Álcool/tratamento farmacológico , Transtornos Induzidos por Álcool/prevenção & controle , Clormetiazol/uso terapêutico , Diazepam/uso terapêutico , Moduladores GABAérgicos/uso terapêutico , Adulto , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos
3.
Pharmacopsychiatry ; 49(4): 170-3, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27145161

RESUMO

We report on the long-term clinical outcome (up to 8 years) of 5 patients who received deep brain stimulation (DBS) of the nucleus accumbens to treat their long-lasting and treatment-resistant alcohol addiction. All patients reported a complete absence of craving for alcohol; 2 patients remained abstinent for many years and 3 patients showed a marked reduction of alcohol consumption. No severe or long-standing side effects occurred. Therefore, DBS could be a promising, novel treatment option for severe alcohol addiction, but larger clinical trials are needed to further investigate the efficacy of DBS in addiction.


Assuntos
Alcoolismo/terapia , Estimulação Encefálica Profunda/métodos , Núcleo Accumbens/fisiologia , Adulto , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Projetos Piloto , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários
5.
Nervenarzt ; 86(5): 595-602, 2015 May.
Artigo em Alemão | MEDLINE | ID: mdl-25631120

RESUMO

BACKGROUND: The term neonaticide describes the act of killing a newborn child by a parent (mostly by the mother) within 24 h after birth. The aim of this study was to establish a classification of female perpetrators using psychopathological, mental, social and biographical characteristics and to make a comparison of the frequency between the old and new federal states in Germany. MATERIAL AND METHODS: In this study a total of 63 female German perpetrators who killed at least one newborn between 1986 and 2009 are portrayed and classified by epidemiological and psychopathological characteristics and personality profiles. After obtaining consent from the public prosecutors responsible, data were collected from forensic psychiatric expert opinions and legally valid court verdicts. A questionnaire was established to answer the questions on the psychopathological, e.g. do the women suffer from a mental disease when killing their newborn(s), mental, e.g. can personality accentuations be elicited, social, e.g. are the women unemployed and biographical characteristics of the women, e.g. how old are the women? Finally, an investigation was carried out using significance tests to find out if there was a significant statistical difference in the frequency of neonaticide between the eastern and western federal states. RESULTS: A cluster analysis based on the descriptive analysis was developed. The cluster analysis provided a foundation for a dichotomous classification of the perpetrators depending on five criteria. The first category contained 32 perpetrators who were on average 21 years old, who were primiparous and who hid, ignored or did not perceive their pregnancy. Most of them still lived with their parents. The perpetrators either did not have a mental disease or suffered from an acute stress disorder. The second category contained 31 perpetrators who were on average 25 years old, who were pluriparous, who hid their pregnancy and who lived with their partner. These women either did not have a mental disease or suffer from a personality disorder. A statistically significant higher incidence was found in the eastern federal states of Germany. CONCLUSION: The presented categorization of female perpetrators into two groups, where the features only show a small degree of overlap, should be taken into consideration in the assessment of the reasons for neonaticide. The typology of female perpetrators is more heterogeneous than previously assumed. The presented typologies and knowledge of conditional constellations involved in neonaticide achieve better prerequisites to be able to recognize persons at risk earlier and to instigate preventive measures.


Assuntos
Criminosos/psicologia , Infanticídio/psicologia , Infanticídio/estatística & dados numéricos , Transtornos Mentais/psicologia , Mães/psicologia , Mulheres/psicologia , Adulto , Distribuição por Idade , Feminino , Alemanha Oriental/epidemiologia , Alemanha Ocidental/epidemiologia , Humanos , Incidência , Recém-Nascido , Transtornos Mentais/epidemiologia , Mães/estatística & dados numéricos , Fatores de Risco , Desemprego/psicologia , Desemprego/estatística & dados numéricos
6.
Psychol Med ; 44(10): 2053-65, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24176247

RESUMO

BACKGROUND: Local structural and metabolic as well as inter-regional connectivity abnormalities have been implicated in the neuropathology of major depressive disorder (MDD). How local tissue properties affect intrinsic functional connectivity is, however, unclear. Using a cross-sectional, multi-modal imaging approach, we investigated the relationship between local cortical tissue abnormalities and intrinsic resting-state functional connectivity (RSFC) in MDD. METHOD: A total of 20 MDD in-patients and 20 healthy controls underwent magnetic resonance imaging at 3 T for structural and functional imaging. Whole-brain cortical thickness was calculated and compared between groups. Regions with reduced cortical thickness defined seeds for subsequent whole-brain RSFC analyses. Contributions of structural tissue abnormalities on inter-regional RSFC were explicitly investigated. RESULTS: Lower cortical thickness was observed in MDD in the right dorsomedial prefrontal cortex (PFC), superior temporal gyrus/temporal pole, middle-posterior cingulate cortex, and dorsolateral PFC. No differences in local fractional amplitude of low-frequency fluctuations were observed. Lower thickness in patients' dorsomedial PFC further directly and selectively affected its RSFC with the precuneus, which was unaffected by symptom severity. No effects of cortical thickness in other regions showing abnormal thickness were observed to influence functional connectivity. CONCLUSIONS: Abnormal cortical thickness in the dorsomedial PFC in MDD patients was observed to selectively and directly affect its intrinsic connectivity with the precuneus in MDD patients independent of depression severity, thereby marking a potential vulnerability for maladaptive mood regulation. Future studies should include an unmedicated sample and replicate findings using independent component analysis to test for morphometric effects on network integrity.


Assuntos
Mapeamento Encefálico/métodos , Transtorno Depressivo Maior/patologia , Rede Nervosa/fisiopatologia , Córtex Pré-Frontal/patologia , Adulto , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiopatologia
7.
Mol Psychiatry ; 17(5): 494-502, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21483431

RESUMO

Biomarkers are now used in many areas of medicine but are still lacking for psychiatric conditions such as schizophrenia (SCZ). We have used a multiplex molecular profiling approach to measure serum concentrations of 181 proteins and small molecules in 250 first and recent onset SCZ, 35 major depressive disorder (MDD), 32 euthymic bipolar disorder (BPD), 45 Asperger syndrome and 280 control subjects. Preliminary analysis resulted in identification of a signature comprised of 34 analytes in a cohort of closely matched SCZ (n=71) and control (n=59) subjects. Partial least squares discriminant analysis using this signature gave a separation of 60-75% of SCZ subjects from controls across five independent cohorts. The same analysis also gave a separation of ~50% of MDD patients and 10-20% of BPD and Asperger syndrome subjects from controls. These results demonstrate for the first time that a biological signature for SCZ can be identified in blood serum. This study lays the groundwork for development of a diagnostic test that can be used as an aid for distinguishing SCZ subjects from healthy controls and from those affected by related psychiatric illnesses with overlapping symptoms.


Assuntos
Biomarcadores/sangue , Esquizofrenia/sangue , Adulto , Síndrome de Asperger/sangue , Transtorno Bipolar/sangue , Estudos de Casos e Controles , Transtorno Depressivo Maior/sangue , Feminino , Humanos , Masculino
8.
Amino Acids ; 45(2): 269-78, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23604405

RESUMO

Nardilysin is a metalloprotease that cleaves peptides, such as dynorphin-A, α-neoendorphin, and glucagon, at the N-terminus of arginine and lysine residues in dibasic moieties. It has various functionally important molecular interaction partners (heparin-binding epidermal growth factor-like growth factor, tumour necrosis factor-α-converting enzyme, neuregulin 1, beta-secretase 1, malate dehydrogenase, P42(IP4)/centaurin-α1, the histone H3 dimethyl Lys4, and others) and is involved in a plethora of normal brain functions. Less is known about possible implications of nardilysin for brain diseases. This review, which includes some of our own recent findings, attempts to summarize the current knowledge on possible roles of nardilysin in Alzheimer disease, Down syndrome, schizophrenia, mood disorders, alcohol abuse, heroin addiction, and cancer. We herein show that nardilysin is a Janus-faced enzyme with regard to brain pathology, being probably neuropathogenic in some diseases, but neuroprotective in others.


Assuntos
Encefalopatias/enzimologia , Encefalopatias/metabolismo , Metaloendopeptidases/metabolismo , Doença de Alzheimer/metabolismo , Neoplasias Encefálicas/metabolismo , Síndrome de Down/metabolismo , Dinorfinas/metabolismo , Endorfinas/metabolismo , Glucagon/metabolismo , Humanos , Transtornos do Humor/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Precursores de Proteínas/metabolismo , Esquizofrenia/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo
9.
Amino Acids ; 44(2): 423-33, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22870827

RESUMO

The cellular uptake of L-arginine and other cationic amino acids (such as L-lysine and L-ornithine) is mainly mediated by cationic amino acid transporter (CAT) proteins. Despite the important roles of cationic amino acid transporters for normal brain functioning and various brain diseases there is currently only fragmentary knowledge about their cellular and regional distribution patterns in the human brain. We mapped the immunohistochemical localization of human cationic amino acid transporters 1, 2 and 3 (hCAT1, 2, and 3) throughout five adult human brains and found a wide but uneven distribution of these transporters. All three hCAT1s were mainly localized in neurons, but were also found in numerous astrocytes, oligodendrocytes, plexus choroideus epithelial cells, and small blood vessels. The highest density of hCAT expressing neurons was observed in the hypothalamus, in some areas of the cerebral cortex, the thalamic reticular nucleus and the caudate nucleus, whereas weak to moderate expression was detected in the hippocampus, the prefrontal cortex (hCAT1 only), pons, brain stem and cerebellum. In contrast to what has been found in rodent brain, we detected hCAT2 and hCAT3 also in astrocytes. Overall, each hCAT has its characteristic, individual cerebral expression patterns, which, however, overlap with the others.


Assuntos
Encéfalo/metabolismo , Transportador 1 de Aminoácidos Catiônicos/metabolismo , Transportador 2 de Aminoácidos Catiônicos/metabolismo , Adulto , Astrócitos/metabolismo , Transportador 1 de Aminoácidos Catiônicos/genética , Transportador 2 de Aminoácidos Catiônicos/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oligodendroglia/metabolismo , Transporte Proteico
10.
Nervenarzt ; 84(11): 1329-44, 2013 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-22911318

RESUMO

Individual and collective acts of violence are mainly a male phenomenon caused by complex interactions of neurobiological and psychosocial factors. Amazingly this topic has not yet played a major role in the clinical psychiatric literature although the disastrous consequences are clearly visible everywhere and although aggression also belongs to the archaic human emotions, such as anxiety, depression and euphoria.The article gives an integrative overview on epidemiological, neurobiological, genetic, neuropathological, neurochemical/hormonal, developmental and psychosocial theories on aggression and violence, including sociocognitive models, hedonistic aspects of violence, effects of violence in the media and processes of childhood socialization.Better knowledge of the broad spectrum of these intensively interacting biological and psychosocial components resulting in violence not only improves our understanding of this calamitous psychosyndrome but can also lead to more effective preventive measures.


Assuntos
Agressão/psicologia , Encéfalo/fisiopatologia , Modelos Psicológicos , Violência/prevenção & controle , Violência/psicologia , Humanos , Masculino
11.
Nervenarzt ; 84(11): 1345-54, 1356-8, 2013 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-24009029

RESUMO

Collective violence, despite its often disastrous consequences has widely been disregarded by psychiatry, as was the case for individual violence. Physical violence is not only an individual, mostly male phenomenon but manifests mainly as collective violence among men in multiple forms. Due to the plentitude of theories and findings on collective violence the present article is limited to a few relevant sociological and neurobiological aspects of collective violence as a group and intergroup phenomenon. A special focus is given to the association of the phylogenetic disposition to group violence and constructions of masculinity, to the potential relevance of mirror neurons for social contagion and to the influence of sociostructural factors for male adolescents joining violence-prone groups. In this context group dynamics such as in-group overevaluation and out-group devaluation are of central importance by stabilizing the male sense of self-worth and legitimizing, normalizing and internalizing violent behavior. Instead of mythologizing, biologizing or banalizing violence, transdisciplinary approaches are necessary to improve violence prevention on different ecological levels being obligated to a culture of nonviolent conflict management.


Assuntos
Agressão/psicologia , Encéfalo/fisiopatologia , Modelos Psicológicos , Transtornos do Comportamento Social/prevenção & controle , Transtornos do Comportamento Social/psicologia , Violência/prevenção & controle , Violência/psicologia , Adolescente , Comportamento do Adolescente/psicologia , Humanos , Masculino , Psicologia
12.
Nervenarzt ; 83(1): 57-63, 2012 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-21305261

RESUMO

In order to clarify psychosocial and psychopathological components that may contribute to causes of running amok, judgements and forensic-psychiatric certificates of 27 amok runners were examined. While in the last 20 years there was no increase of amok events in general, a remarkable increase in so-called school shootings occurred; 74% of the culprits had a history of psychiatric disorder, most importantly schizophrenic psychoses, affective disorder or alcoholism. According to the forensic psychiatric certificates, 70% were not or not fully responsible for the crime. Three prototypes of amok runners were found: (1) adolescents with long-term difficulties at school or apprenticeship and suicidal ideas; (2) persons suffering from paranoid psychoses; and (3) adults with personality disorders after breakdowns of close social relationships. Despite these predisposing factors it remains unknown which pathological conditions of brain function finally cause this most deleterious form of violence.


Assuntos
Criminosos/psicologia , Criminosos/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Violência/psicologia , Violência/estatística & dados numéricos , Adolescente , Adulto , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Adulto Jovem
13.
Psychol Med ; 41(8): 1641-50, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21144117

RESUMO

BACKGROUND: The concept of narcissism has been much researched in psychoanalysis and especially in self psychology. One of the hallmarks of narcissism is altered emotion, including decreased affective resonance (e.g. empathy) with others, the neural underpinnings of which remain unclear. The aim of our exploratory study was to investigate the psychological and neural correlates of empathy in two groups of healthy subjects with high and low narcissistic personality trait. We hypothesized that high narcissistic subjects would show a differential activity pattern in regions such as the anterior insula that are typically associated with empathy. METHOD: A sample of 34 non-clinical subjects was divided into high (n=11) and low (n=11) narcissistic groups according to the 66th and 33rd percentiles of their scores on the Narcissism Inventory (NI). Combining the psychological, behavioral and neuronal [i.e. functional magnetic resonance imaging (fMRI)] measurements of empathy, we compared the high and low narcissistic groups of subjects. RESULTS: High narcissistic subjects showed higher scores on the Symptom Checklist-90 - Revised (SCL-90-R) and the 20-item Toronto Alexithymia Scale (TAS-20) when compared to low narcissistic subjects. High narcissistic subjects also showed significantly decreased deactivation during empathy, especially in the right anterior insula. CONCLUSIONS: Psychological and neuroimaging data indicate respectively higher degrees of alexithymia and lower deactivation during empathy in the insula in high narcissistic subjects. Taken together, our preliminary findings demonstrate, for the first time, psychological and neuronal correlates of narcissism in non-clinical subjects. This might stipulate both novel psychodynamic conceptualization and future psychological-neuronal investigation of narcissism.


Assuntos
Encéfalo/fisiologia , Emoções , Narcisismo , Adulto , Emoções/fisiologia , Empatia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Personalidade/fisiologia , Inventário de Personalidade , Escalas de Graduação Psiquiátrica
14.
Amino Acids ; 40(2): 453-65, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20563878

RESUMO

Agmatinase, an ureohydrolase belonging to the arginase family, is widely expressed in mammalian tissues including the brain. Here, it may serve two different functions, the inactivation of the arginine derivative agmatine, a putative neurotransmitter, and the formation of the diamine putrescine. In order to identify the cellular sources of agmatinase expression in the brain, we generated a polyclonal monospecific antibody against recombinant rat agmatinase. With immunocytochemistry, selected areas of rat and human brain were screened. Clearly, in both species agmatinase-like immunoreactivity was predominantly detected in distinct populations of neurons, especially cortical interneurons. Also, principal neurons in limbic regions like the habenula and in the cerebellum robustly expressed agmatinase protein. When comparing the overall agmatinase expression with immunocytochemical data available for agmatine and polyamine biosynthetic enzymes, the observed pattern may argue in favor of an agmatine inactivating function rather than fueling the alternative pathway of polyamine synthesis. The putative neurotransmitter agmatine is seemingly involved with mental disorders. Therefore, agmatinase may be similarly important for pathogenesis. The normal expression profile of the protein as described here may therefore be altered under pathological conditions.


Assuntos
Agmatina/metabolismo , Encéfalo/enzimologia , Transdução de Sinais , Ureo-Hidrolases/metabolismo , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/enzimologia , Neurônios/metabolismo , Ratos , Ratos Wistar , Ureo-Hidrolases/genética
15.
Psychol Med ; 40(4): 557-67, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19671211

RESUMO

BACKGROUND: The habenular complex is composed of important relay nuclei linking the limbic forebrain to the midbrain and brain stem nuclei. Based on clinical observations, experiments with animals and theoretical considerations, it has been speculated that this brain area might be involved in psychiatric diseases (i.e. schizophrenia and depression). However, evidence in favour of this hypothesis is still lacking because the human habenular complex has rarely been studied with regard to mental illness. METHOD: We examined habenular volumes in post-mortem brains of 17 schizophrenia patients, 14 patients with depression (six patients with major depression and eight patients with bipolar depression) and 13 matched controls. We further determined the neuronal density, cell number and cell area of the medial habenular nuclei of the same cohorts using a counting box and a computer-assisted instrument. RESULTS: Significantly reduced habenular volumes of the medial and lateral habenula were estimated in depressive patients in comparison to normal controls and schizophrenia patients. We also found a reduction in neuronal cell number and cell area in depressive patients for the right side compared to controls and schizophrenia patients. No such changes were seen in schizophrenia. CONCLUSIONS: Our anatomical data argue against prominent structural alterations of the habenular nuclei in schizophrenia but demonstrate robust alterations in depressive patients. We are currently applying immunohistochemical markers to better characterize neuronal subpopulations of this brain region in schizophrenia and depression.


Assuntos
Habenula/anormalidades , Habenula/patologia , Transtornos do Humor/patologia , Transtornos do Humor/psicologia , Esquizofrenia , Adulto , Idoso , Contagem de Células , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/diagnóstico , Rede Nervosa/patologia , Esquizofrenia/diagnóstico , Índice de Gravidade de Doença
16.
Pharmacopsychiatry ; 43(3): 99-109, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20131206

RESUMO

BACKGROUND: Growing evidence indicates the role of the thalamus in schizophrenia. The ventral part of the thalamus has been investigated in a few post-mortem studies, suggesting a possible neurodevelopmental etiology of the reduced neuron number. METHODS: Here we adapt a neurodevelopmental animal model, the neonatal excitotoxic brain lesion, to the ventral thalamus (VT) of Sprague-Dawley rats. At postnatal day (PD) 7 male pups were bilaterally infused into the VT using ibotenic acid (IBA) or artificial cerebrospinal fluid. Repeated measurements of prepulse inhibition (PPI) of the acoustic startle response, reviewed as a measure of sensorimotor gating deficits in neuropsychiatric disorders such as schizophrenia, were performed during puberty and adulthood. RESULTS: IBA animals showed lower PPI (p<0.001) compared to controls. The extent of VT lesions correlated negatively with PPI levels (p<0.001). PPI deficits in IBA animals were observed at PD 43 and PPI levels increased significantly after puberty without reaching control levels. Acute or subchronic clozapine treatment did not significantly restore low PPI in IBA rats. CONCLUSION: The present data suggest that the VT may be involved in the PPI deficits observed in schizophrenia.


Assuntos
Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Ibotênico/farmacologia , Filtro Sensorial/efeitos dos fármacos , Tálamo/fisiopatologia , Fatores Etários , Envelhecimento , Animais , Animais Recém-Nascidos , Antipsicóticos/farmacologia , Clozapina/farmacologia , Modelos Animais de Doenças , Masculino , Ratos , Reflexo de Sobressalto/efeitos dos fármacos , Reflexo de Sobressalto/fisiologia , Esquizofrenia/fisiopatologia , Filtro Sensorial/fisiologia , Tálamo/efeitos dos fármacos
19.
Mol Psychiatry ; 13(9): 878-96, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18504422

RESUMO

Many studies in recent years suggest that schizophrenia is a synaptic disease that crucially involves a hypofunction of N-methyl-D-aspartate receptor-mediated signaling. However, at present it is unclear how these pathological processes are reflected in the protein content of the synapse. We have employed two-dimensional gel electrophoresis in conjunction with mass spectrometry to characterize and compare the synaptic proteomes of the human left dorsolateral prefrontal cortex in chronic schizophrenia and of the cerebral cortex of rats treated subchronically with ketamine. We found consistent changes in the synaptic proteomes of human schizophrenics and in rats with induced ketamine psychosis compared to controls. However, commonly regulated proteins between both groups were very limited and only prohibitin was found upregulated in both chronic schizophrenia and the rat ketamine model. Prohibitin, however, could be a new potential marker for the synaptic pathology of schizophrenia and might be causally involved in the disease process.


Assuntos
Transtornos Mentais/patologia , Proteoma/metabolismo , Proteínas Repressoras/metabolismo , Esquizofrenia/patologia , Sinapses/metabolismo , Adulto , Análise de Variância , Animais , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/patologia , Modelos Animais de Doenças , Eletroforese em Gel Bidimensional/métodos , Feminino , Proteínas de Fluorescência Verde/biossíntese , Humanos , Ketamina , Masculino , Espectrometria de Massas/métodos , Transtornos Mentais/induzido quimicamente , Pessoa de Meia-Idade , Análise Numérica Assistida por Computador , Proibitinas , Ratos , Ratos Sprague-Dawley , Estudos Retrospectivos , Esquizofrenia/metabolismo , Frações Subcelulares/metabolismo , Sinapses/efeitos dos fármacos , Transfecção
20.
Neuroscience ; 154(2): 496-503, 2008 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-18472341

RESUMO

S100B (member of a family of proteins that are 100% soluble in ammonium sulfate at neutral pH) has been widely used as astrocyte marker in animal models and in human brain diseases. Recent studies revealed S100B-immunopositivity in oligodendrocytes and O2A oligodendroglial progenitor cells. It is unknown, however, if oligodendrocytes produce S100B themselves, or if the S100B-immunolabeling is caused by binding or absorption of the protein. To address this question, S100B expression and protein release were analyzed in a highly pure oligodendrocytic OLN-93 cell line (from rat), in the astrocytic C6 cell line (from rat) and primary astrocytes. S100B was gene expressed in all cultures, as revealed by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. OLN-93 cells and glial fibrillary acidic protein (GFAP)-negative astrocytes expressed the multiligand receptor for advanced glycation end products (RAGE). S100B protein levels were determined in supernatants and cell homogenates by immunoluminometry under normal conditions and after serum and glucose deprivation (SGD). SGD led to a several-fold increased release of S100B (after 6 and 24 h), which was particularly pronounced in primary astrocytes. Increased S100B in cell homogenates was most notable in OLN-93 cells under SGD, indicating activated S100B synthesis. These cells also showed the highest percentage of dead cells, as determined by propidium iodide-positivity, after SGD. Incubation with 0.5, 2 and 5 microg/l exogenous S100B was not toxic to OLN-93 cells. In conclusion, OLN-93 cells produce more S100B under SGD than astrocytes and are more susceptible to cell death upon SGD, which provokes leakage of S100B. Our data indicate active S100B secretion from astrocytes under SGD since highly elevated levels of S100B were detected in the supernatant despite a low percentage of dead cells. The experimental results provide further evidence for a production/release of S100B in/from oligodendrocytes, e.g. in metabolic stress conditions like cerebral ischemia. Studies on S100B in bodily fluids should be carefully interpreted in order to avoid misleading hypotheses concerning the specific involvement of astrocytes, due to the various cellular sources of S100B.


Assuntos
Glucose/deficiência , Fatores de Crescimento Neural/biossíntese , Oligodendroglia/metabolismo , Proteínas S100/biossíntese , Animais , Animais Recém-Nascidos , Astrócitos/metabolismo , Astrócitos/ultraestrutura , Linhagem Celular Tumoral , Células Cultivadas , Corantes , Meios de Cultura Livres de Soro , Fluoresceínas , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Fatores de Crescimento Neural/metabolismo , Oligodendroglia/ultraestrutura , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/metabolismo
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