No description available.

No description available.

L’excitotoxicité est un mécanisme physiopathologique majeur impliqué dans la pathogenèse de la déficience en thiamine (DT). Dans les régions cérébrales vulnérables à la DT, on observe une mort cellulaire induite par excitotoxicité dont l’origine semble être la conséquence d’une perturbation du métabolisme énergétique mitochondrial, d’une dépolarisation membranaire soutenue et d’une diminution de l’absorption du glutamate par les astrocytes suite à la diminution de l’expression des transporteurs EAAT1 et EAAT2. Il est clairement établi que le glutamate joue un rôle central dans l’excitotoxicité lors de la DT. Ainsi, la mise en évidence des mécanismes impliqués dans la diminution de l’expression des transporteurs du glutamate est essentielle à la compréhension de la physiopathologie de la DT. L’objectif de cette thèse consiste en l’étude de la régulation des transporteurs astrocytaires du glutamate et la mise au point de stratégies thérapeutiques ciblant la pathogenèse de l’excitotoxicité lors de l’encéphalopathie consécutive à la DT. Les principaux résultats de cette thèse démontrent des perturbations des transporteurs du glutamate à la fois dans des modèles animaux de DT et dans des astrocytes en culture soumis à une DT. La DT se caractérise par la perte du variant d’épissage GLT-1b codant pour un transporteur du glutamate dans le thalamus et le colliculus inférieur, les régions cérébrales affectées lors d’une DT, en l’absence de modification des niveaux d’ARNm. Ces résultats suggèrent une régulation post-transcriptionnelle de l’expression des transporteurs du glutamate en condition de DT. Les études basées sur l’utilisation d’inhibiteurs spécifiques des facteurs de transcription NFkB et de l’enzyme nucléaire poly(ADP)ribose polymérase-1 (PARP-1) démontrent que la régulation de l’expression du transporteur GLT-1 est sous le contrôle de voies de signalisation NFkB dépendantes de PARP-1. Cette étude démontre une augmentation de l’activation de PARP-1 et de NFkB dans les régions vulnérables chez le rat soumis à une DT et en culture d’astrocytes DT. L’inhibition pharmacologique du facteur de transcription NFkB par le PDTC induit une augmentation des niveaux d’expression de GLT-1, tandis que l’inhibition de PARP-1 par le DPQ conduit à l’inhibition de l’hyperactivation de NFkB observée lors de DT. L’ensemble de ces résultats met en évidence un nouveau mécanisme de régulation des transporteurs du glutamate par l’activation de PARP-1. L’accumulation de lactate est une caractéristique de la DT. Un traitement avec le milieu de culture d’astrocytes en condition de DT sur des cultures d’astrocytes naïfs induit une diminution de l’expression de GLT-1 ainsi qu’une inhibition de la capacité d’absorption du glutamate par les astrocytes naïfs. En revanche, l’administration de lactate exogène ne modifie pas le niveau d’expression protéique de GLT-1. Ainsi, des facteurs solubles autres que le lactate sont sécrétés par des astrocytes en condition de perturbation métabolique et peuvent potentiellement réguler l’activité des transporteurs du glutamate et contribuer à la pathogenèse du syncytium astroglial. En outre, la ceftriaxone, un antibiotique de la famille des β-lactamines, augmente de façon différentielle l’expression du variant-d’épissage GLT-1 dans le colliculus inférieur chez le rat DT et en culture d’astrocytes DT. Ces résultats suggèrent que la ceftriaxone peut constituer une avenue thérapeutique dans la régulation de l’activité des transporteurs du glutamate lors de DT. Pour conclure, la mort cellulaire d’origine excitotoxique lors de DT survient en conséquence d’une dysfonction mitochondriale associée à une perturbation du métabolisme énergétique cérébral. La modification de l’expression des transporteurs du gluatamate est sous le contrôle des voies de signalisation NFkB dépendantes du facteur PARP-1. De plus, l’inhibition métabolique et l’augmentation des sécrétions de lactate observées lors de DT peuvent également constituer un autre mécanisme physiopathologique expliquant la diminution d’expression des transporteurs de glutamate. Enfin, la ceftriaxone pourrait représenter une stratégie thérapeutique potentielle dans le traitement de la régulation de l’expression des transporteurs du glutamate et de la perte neuronale associés à l’excitotoxicité observée lors de DT. / Excitotoxicity has been implicated as a major pathophysiological mechanism in the pathogenesis of thiamine deficiency (TD). Excitotoxic-mediated cell death is localized in areas of focal vulnerability in TD and may occur as a consequence of impairment in mitochondrial energy metabolism, sustained cell membrane depolarization and decreased uptake of glutamate by astrocytes due to the loss of excitatory amino acid transporters, (EAAT1 and EAAT2). Over the years, a number of studies have identified glutamate as being a major contributor to excitotoxicity in the pathophysiology of TD. Thus, downregulation of astrocytic glutamate transporters resulting in excitotoxicity is a key feature of TD and understanding the regulation of these transporters is essential to understanding the pathophysiology of the disorder. The objective of the present thesis project was to examine the underlying basis of astrocytic glutamate transporter regulation during TD encephalopathy. Major findings of the studies presented in this thesis project provide evidence for glutamate transporter abnormalities in TD animal models and astrocyte cultures exposed to TD. TD results in the loss of the glutamate transporter splice variant-1b (GLT-1b) in vulnerable areas of brain, i.e. thalamus and inferior colliculus, with no significant alteration in the mRNA levels of the transporters, suggesting that glutamate transporter regulation under conditions of TD is a posttranscriptional event. Studies using a specific inhibitor of the transcription factor, Nuclear factor-kappa B (NF-κB) and a nuclear enzyme poly (ADP)ribose polymerase-1 (PARP-1) provided evidence for the regulation of GLT-1 by PARP-1 dependent NF-κB signalling pathways. The major findings of this study suggested an increase in the activation of PARP-1 and NF-κB molecule in the vulnerable areas of TD rat brain and TD astrocyte cultures. Pharmacological inhibition of NF-κB showed an increase in the levels of GLT-1, while inhibition of PARP-1 using a specific PARP-1 inhibitor, DPQ inhibited the increased activation of NF-κB that was observed during TD. Overall results of this finding provided evidence for a mechanism involving PARP-1 activation in the regulation of glutamate transporters. Given the increased lactate accumulation as a classical feature of TD, we studied the effect of soluble factors produced by astrocytes on glutamate transporter function. Treatment of naïve astrocyte cultures with TD conditioned media resulted in decreased levels of GLT-1 and inhibition of glutamate uptake capacity concomitant with a loss of mitochondrial membrane potential. Administration of exogenous lactic acid produced a similar reduction in glutamate uptake to that resulting from conditioned media. However, lactic acid treatment did not result in a change in GLT-1 protein levels. In addition, the pro-inflammatory cytokine TNF-α was shown to be increased in astrocytes treated with TD along with elevated levels of the phospho-IκB fragment, indicative of increased activation of NFκB. Inhibition of NFκB led to an amelioration of the decrease in GLT-1 that occurs in TD, along with recovery of glutamate uptake. Thus, soluble factors released from astrocytes under conditions of metabolic impairment such as lactate and TNF-α impairment appear to exert a regulatory influence on glutamate transporter function. Ceftriaxone, a β-lactam antibiotic, has the ability to differentially stimulate GLT-1b (splice-variant) expression in the inferior colliculus in TD rats and under in vitro conditions with TD astrocyte cultures. Thus, ceftriaxone may be a potential therapeutic strategy in the regulation of glutamate transporter function during TD. In summary, excitotoxic cell death in TD occurs as a consequence of mitochondrial dysfunction associated with cerebral energy impairment and abnormal glutamate transporter status. A major underlying mechanism for glutamate transporter abnormalities is mediated by PARP-1 dependent NF-κB signaling pathways. In addition, metabolic inhibition with substantial production of lactate and TNF-α may be perhaps another mechanism responsible for glutamate transporter downregulation in TD.

No description available.

Introdução: o crack é uma forma extremamente aditiva de cocaína, provocando intensa fissura e um comportamento persistente e intenso de busca pela droga com negligência da alimentação. A alimentação insuficiente pode levar à carência de tiamina. O uso de latas e folhas de alumínio na confecção de cachimbos para o consumo de crack aumenta a exposição de usuários de crack a este metal. Deficiência de tiamina somada a acúmulo cerebral de alumínio pode inibir o metabolismo energético dependente da glicose, levando à neurodegeneração e, possivelmente, à encefalopatia de Wernicke. Objetivos: avaliação dos níveis sanguíneos de tiamina difosfato e de alumínio de dependentes de crack e comparação com os de controles. Método: estudo transversal controlado, avaliou 35 dependentes de crack e 35 controles, do sexo masculino, com 18 anos ou mais. Os casos foram recrutados entre pacientes internados na Unidade de Adição do Hospital de Clínicas de Porto Alegre ou na Emergência em Saúde Mental IAPI, os controles foram recrutados entre as pessoas que circulam na área ambulatorial do Hospital de Clínicas de Porto Alegre. Todos participantes tiveram seu peso e estatura medidos e sangue coletado para determinação dos níveis de tiamina difosfato e de alumínio. Os casos passaram, também, por uma breve avaliação neurológica. Resultados: as características dos casos são semelhantes à amostra do principal estudo nacional sobre o uso de crack no Brasil: sexo masculino, cerca de 30 anos de idade, com baixa escolaridade, desempregados, usuários de múltiplas substâncias psicoativas, consumidores de crack há aproximadamente 8 anos. O índice de massa corporal dos casos foi significativamente mais baixo (p<0.0001). Seis casos (17.65%) apresentaram índice de massa corporal abaixo do normal. Dois casos apresentaram nível de tiamina abaixo dos valores de referência, enquanto os níveis dos controles estavam acima deste limite. Comparando os resultados do primeiro quartil do nível sanguíneo de tiamina dos casos (N= 9; mediana 3.6μg/dL, amplitude interquartil 3.05μg/dL -4.10μg/dL) com o dos controles (N=14, mediana 4.3μg/dL, amplitude interquartil 3.7μg/dL-4.4μg/dL), os casos apresentaram níveis significativamente mais baixos (p=0.024). Os níveis de alumínio dos casos que tiveram as amostras de sangue coletadas até 24h após o último consumo da substância, foram maiores (mediana1.85μg/L, amplitude interquartil0.65-4.425μg/L) que os dos controles (mediana 0.95μg/L, amplitude interquartil 0.7-1.22μg/L), mas esta diferença não atingiu significância estatística (p=0.07). Conclusões: dependentes de crack tem índice de massa corporal menor e estão mais expostos ao alumínio que os controles. Alguns tem deficiência de tiamina, a qual pode levar à encefalopatia de Wernicke e declínio cognitivo. Portanto, tiamina parenteral profilática deve ser considerada para alguns dependentes de crack. / Background: Crack-cocaine is an extremely additive form of cocaine and its compulsive use can last days until exhaustion, driving its users to neglect feeding. Poor feeding may cause thiamine deficiency. In Brazil, crack-cocaine is usually smoked in pipes made of aluminum cans or with aluminum foils. Insufficient brain levels of thiamine plus brain aluminum accumulation, may impair glucose energy metabolism, promoting neurodegeneration and possibly Wernicke’s encephalopathy. Objectives: The aim of this study was to evaluate thiamine and aluminum blood levels in crack-cocaine addicts and compare them to healthy controls. Methods: cross-sectional controlled study, included 35 crack-cocaine addicts and 35 healthy controls, all males, 18 or older. Cases were recruited at the Addiction Unit of Hospital de Clínicas de Porto Alegre or at the Mental Health Emergency IAPI, controls were recruited between people circulating in the outpatient clinic area of Hospital de Clínicas de Porto Alegre. Weight and height were measured and blood samples collected for determination of thiamine diphosphate and aluminum levels. Cases were also submitted to a brief neurological examination. Results: cases characteristics were similar to the sample of the main national study related to crack-cocaine use in Brazil: mainly males, about 30 years old, with low education level, unemployed, multiple drug abusers, consuming crack-cocaine for approximately 8 years. Body mass index was significantly lower in cases (p<0.0001). Six cases (17.65%) had body mass index lower than normal, while no control was below this limit. Two cases presented thiamine levels below the laboratory reference range, while controls were all above this limit. Comparing the lower quartile of thiamine blood levels, cases (3.6 μg/dL) had significantly lower levels of thiamine than controls (4.3μg/dL) (p=0.024). Blood aluminum median of crack-cocaine addicts (1.85μg/L, interquartile range 0.65-4.425μg/L) whose samples were drawn until 24h after last drug consumption was higher than controls (0.95μg/L, interquartile range 0.7-1.22μg/L), but the difference did not achieve statistical significance (p=0.07). Conclusions: Crack-cocaine addicts have lower BMI and are more exposed to aluminum in comparison to healthy controls. Also, some of them have thiamine deficiency which may lead to Wernicke’s encephalopathy and cognitive impairment. Thus, prophylactic parenteral thiamine should be considered to some crack-cocaine addicts.

Thesis (M.S.)--State University of New York at Binghamton, Department of Psychology, 2009. / Includes bibliographical references.

Introdução: o crack é uma forma extremamente aditiva de cocaína, provocando intensa fissura e um comportamento persistente e intenso de busca pela droga com negligência da alimentação. A alimentação insuficiente pode levar à carência de tiamina. O uso de latas e folhas de alumínio na confecção de cachimbos para o consumo de crack aumenta a exposição de usuários de crack a este metal. Deficiência de tiamina somada a acúmulo cerebral de alumínio pode inibir o metabolismo energético dependente da glicose, levando à neurodegeneração e, possivelmente, à encefalopatia de Wernicke. Objetivos: avaliação dos níveis sanguíneos de tiamina difosfato e de alumínio de dependentes de crack e comparação com os de controles. Método: estudo transversal controlado, avaliou 35 dependentes de crack e 35 controles, do sexo masculino, com 18 anos ou mais. Os casos foram recrutados entre pacientes internados na Unidade de Adição do Hospital de Clínicas de Porto Alegre ou na Emergência em Saúde Mental IAPI, os controles foram recrutados entre as pessoas que circulam na área ambulatorial do Hospital de Clínicas de Porto Alegre. Todos participantes tiveram seu peso e estatura medidos e sangue coletado para determinação dos níveis de tiamina difosfato e de alumínio. Os casos passaram, também, por uma breve avaliação neurológica. Resultados: as características dos casos são semelhantes à amostra do principal estudo nacional sobre o uso de crack no Brasil: sexo masculino, cerca de 30 anos de idade, com baixa escolaridade, desempregados, usuários de múltiplas substâncias psicoativas, consumidores de crack há aproximadamente 8 anos. O índice de massa corporal dos casos foi significativamente mais baixo (p<0.0001). Seis casos (17.65%) apresentaram índice de massa corporal abaixo do normal. Dois casos apresentaram nível de tiamina abaixo dos valores de referência, enquanto os níveis dos controles estavam acima deste limite. Comparando os resultados do primeiro quartil do nível sanguíneo de tiamina dos casos (N= 9; mediana 3.6μg/dL, amplitude interquartil 3.05μg/dL -4.10μg/dL) com o dos controles (N=14, mediana 4.3μg/dL, amplitude interquartil 3.7μg/dL-4.4μg/dL), os casos apresentaram níveis significativamente mais baixos (p=0.024). Os níveis de alumínio dos casos que tiveram as amostras de sangue coletadas até 24h após o último consumo da substância, foram maiores (mediana1.85μg/L, amplitude interquartil0.65-4.425μg/L) que os dos controles (mediana 0.95μg/L, amplitude interquartil 0.7-1.22μg/L), mas esta diferença não atingiu significância estatística (p=0.07). Conclusões: dependentes de crack tem índice de massa corporal menor e estão mais expostos ao alumínio que os controles. Alguns tem deficiência de tiamina, a qual pode levar à encefalopatia de Wernicke e declínio cognitivo. Portanto, tiamina parenteral profilática deve ser considerada para alguns dependentes de crack. / Background: Crack-cocaine is an extremely additive form of cocaine and its compulsive use can last days until exhaustion, driving its users to neglect feeding. Poor feeding may cause thiamine deficiency. In Brazil, crack-cocaine is usually smoked in pipes made of aluminum cans or with aluminum foils. Insufficient brain levels of thiamine plus brain aluminum accumulation, may impair glucose energy metabolism, promoting neurodegeneration and possibly Wernicke’s encephalopathy. Objectives: The aim of this study was to evaluate thiamine and aluminum blood levels in crack-cocaine addicts and compare them to healthy controls. Methods: cross-sectional controlled study, included 35 crack-cocaine addicts and 35 healthy controls, all males, 18 or older. Cases were recruited at the Addiction Unit of Hospital de Clínicas de Porto Alegre or at the Mental Health Emergency IAPI, controls were recruited between people circulating in the outpatient clinic area of Hospital de Clínicas de Porto Alegre. Weight and height were measured and blood samples collected for determination of thiamine diphosphate and aluminum levels. Cases were also submitted to a brief neurological examination. Results: cases characteristics were similar to the sample of the main national study related to crack-cocaine use in Brazil: mainly males, about 30 years old, with low education level, unemployed, multiple drug abusers, consuming crack-cocaine for approximately 8 years. Body mass index was significantly lower in cases (p<0.0001). Six cases (17.65%) had body mass index lower than normal, while no control was below this limit. Two cases presented thiamine levels below the laboratory reference range, while controls were all above this limit. Comparing the lower quartile of thiamine blood levels, cases (3.6 μg/dL) had significantly lower levels of thiamine than controls (4.3μg/dL) (p=0.024). Blood aluminum median of crack-cocaine addicts (1.85μg/L, interquartile range 0.65-4.425μg/L) whose samples were drawn until 24h after last drug consumption was higher than controls (0.95μg/L, interquartile range 0.7-1.22μg/L), but the difference did not achieve statistical significance (p=0.07). Conclusions: Crack-cocaine addicts have lower BMI and are more exposed to aluminum in comparison to healthy controls. Also, some of them have thiamine deficiency which may lead to Wernicke’s encephalopathy and cognitive impairment. Thus, prophylactic parenteral thiamine should be considered to some crack-cocaine addicts.

Introdução: o crack é uma forma extremamente aditiva de cocaína, provocando intensa fissura e um comportamento persistente e intenso de busca pela droga com negligência da alimentação. A alimentação insuficiente pode levar à carência de tiamina. O uso de latas e folhas de alumínio na confecção de cachimbos para o consumo de crack aumenta a exposição de usuários de crack a este metal. Deficiência de tiamina somada a acúmulo cerebral de alumínio pode inibir o metabolismo energético dependente da glicose, levando à neurodegeneração e, possivelmente, à encefalopatia de Wernicke. Objetivos: avaliação dos níveis sanguíneos de tiamina difosfato e de alumínio de dependentes de crack e comparação com os de controles. Método: estudo transversal controlado, avaliou 35 dependentes de crack e 35 controles, do sexo masculino, com 18 anos ou mais. Os casos foram recrutados entre pacientes internados na Unidade de Adição do Hospital de Clínicas de Porto Alegre ou na Emergência em Saúde Mental IAPI, os controles foram recrutados entre as pessoas que circulam na área ambulatorial do Hospital de Clínicas de Porto Alegre. Todos participantes tiveram seu peso e estatura medidos e sangue coletado para determinação dos níveis de tiamina difosfato e de alumínio. Os casos passaram, também, por uma breve avaliação neurológica. Resultados: as características dos casos são semelhantes à amostra do principal estudo nacional sobre o uso de crack no Brasil: sexo masculino, cerca de 30 anos de idade, com baixa escolaridade, desempregados, usuários de múltiplas substâncias psicoativas, consumidores de crack há aproximadamente 8 anos. O índice de massa corporal dos casos foi significativamente mais baixo (p<0.0001). Seis casos (17.65%) apresentaram índice de massa corporal abaixo do normal. Dois casos apresentaram nível de tiamina abaixo dos valores de referência, enquanto os níveis dos controles estavam acima deste limite. Comparando os resultados do primeiro quartil do nível sanguíneo de tiamina dos casos (N= 9; mediana 3.6μg/dL, amplitude interquartil 3.05μg/dL -4.10μg/dL) com o dos controles (N=14, mediana 4.3μg/dL, amplitude interquartil 3.7μg/dL-4.4μg/dL), os casos apresentaram níveis significativamente mais baixos (p=0.024). Os níveis de alumínio dos casos que tiveram as amostras de sangue coletadas até 24h após o último consumo da substância, foram maiores (mediana1.85μg/L, amplitude interquartil0.65-4.425μg/L) que os dos controles (mediana 0.95μg/L, amplitude interquartil 0.7-1.22μg/L), mas esta diferença não atingiu significância estatística (p=0.07). Conclusões: dependentes de crack tem índice de massa corporal menor e estão mais expostos ao alumínio que os controles. Alguns tem deficiência de tiamina, a qual pode levar à encefalopatia de Wernicke e declínio cognitivo. Portanto, tiamina parenteral profilática deve ser considerada para alguns dependentes de crack. / Background: Crack-cocaine is an extremely additive form of cocaine and its compulsive use can last days until exhaustion, driving its users to neglect feeding. Poor feeding may cause thiamine deficiency. In Brazil, crack-cocaine is usually smoked in pipes made of aluminum cans or with aluminum foils. Insufficient brain levels of thiamine plus brain aluminum accumulation, may impair glucose energy metabolism, promoting neurodegeneration and possibly Wernicke’s encephalopathy. Objectives: The aim of this study was to evaluate thiamine and aluminum blood levels in crack-cocaine addicts and compare them to healthy controls. Methods: cross-sectional controlled study, included 35 crack-cocaine addicts and 35 healthy controls, all males, 18 or older. Cases were recruited at the Addiction Unit of Hospital de Clínicas de Porto Alegre or at the Mental Health Emergency IAPI, controls were recruited between people circulating in the outpatient clinic area of Hospital de Clínicas de Porto Alegre. Weight and height were measured and blood samples collected for determination of thiamine diphosphate and aluminum levels. Cases were also submitted to a brief neurological examination. Results: cases characteristics were similar to the sample of the main national study related to crack-cocaine use in Brazil: mainly males, about 30 years old, with low education level, unemployed, multiple drug abusers, consuming crack-cocaine for approximately 8 years. Body mass index was significantly lower in cases (p<0.0001). Six cases (17.65%) had body mass index lower than normal, while no control was below this limit. Two cases presented thiamine levels below the laboratory reference range, while controls were all above this limit. Comparing the lower quartile of thiamine blood levels, cases (3.6 μg/dL) had significantly lower levels of thiamine than controls (4.3μg/dL) (p=0.024). Blood aluminum median of crack-cocaine addicts (1.85μg/L, interquartile range 0.65-4.425μg/L) whose samples were drawn until 24h after last drug consumption was higher than controls (0.95μg/L, interquartile range 0.7-1.22μg/L), but the difference did not achieve statistical significance (p=0.07). Conclusions: Crack-cocaine addicts have lower BMI and are more exposed to aluminum in comparison to healthy controls. Also, some of them have thiamine deficiency which may lead to Wernicke’s encephalopathy and cognitive impairment. Thus, prophylactic parenteral thiamine should be considered to some crack-cocaine addicts.

The main aim of this dissertation was to investigate the difference in neural language patternsrelated to language ability in healthy adults. The focus lies on unraveling the contributions of theright‐hemispheric homologues to Broca’s area in the inferior frontal gyrus (IFG) and Wernicke’s areain the posterior temporal and inferior parietal lobes. The functions of these regions are far from fullyunderstood at present. Two study populations consisting of healthy adults and a small group ofpeople with generalized epilepsy were investigated. Individual performance scores in tests oflanguage ability were correlated with brain activation obtained with functional magnetic resonanceimaging during semantic and word fluency tasks. Performance‐dependent differences were expectedin the left‐hemispheric Broca’s and Wernicke’s area and in their right‐hemispheric counterparts. PAPER I revealed a shift in laterality towards right‐hemispheric IFG and posterior temporal lobeactivation, related to high semantic performance. The whole‐brain analysis results of PAPER IIrevealed numerous candidate regions for language ability modulation. PAPER II also confirmed thefinding of PAPER I, by showing several performance‐dependent regions in the right‐hemispheric IFGand the posterior temporal lobe. In PAPER III, a new study population of healthy adults was tested.Again, the right posterior temporal lobe was related to high semantic performance. A decrease in lefthemisphericIFG activation could be linked to high word fluency ability. In addition, task difficultywas modulated. Increased task complexity showed to correlate positively with bilateral IFGactivation. Lastly, PAPER IV investigated anti‐correlated regions. These regions are commonly knownas the default mode network (DMN) and are normally suppressed during cognitive tasks. It wasfound that people with generalized epilepsy had an inadequate suppression of regions in the DMN,and showed poorer performance in a complex language test. The results point to neural adaptabilityin the IFG and temporal lobe. Decreased left‐lateralization of the IFG and increased rightlateralizationof the posterior temporal lobe are proposed as characteristics of individuals with highlanguage ability.

Für die Zuweisung von Genus im Deutschen wurden verschiedene Regeln vorgeschlagen. Genuszuweisung kann beispielsweise auf der Grundlage von Suffixregeln erfolgen. Diesen Regeln zufolge sind Derivations- und Diminutivsuffixe zuverlässige Genusindikatoren. Es finden sich nur wenige Ausnahmen zu diesen Regeln. Andere Nomen hingegen scheinen keine Genustransparenz zu haben. Ziel der durchgeführten Studien ist zu prüfen, inwieweit gesunde sowie aphasische Sprecher von formalen Genusindikatoren profitieren. Die Ergebnisse deuten darauf hin, daß gesunde Sprecher des Deutschen, anders als im Französischen oder Italienischen, in einer Genuszuweisungsaufgabe nicht von der Transparenz der Stimuli profitieren. Es wurden keine Reaktionszeitunterschiede zwischen der transparenten und intransparenten Bedingung gemessen. Aphasische Sprecher hingegen machen in der transparenten Bedingung weniger Fehler bei der Genuszuweisung als in der intransparenten Bedingung. Diese Ergebnisse werden im Kontext aktueller Sprachverarbeitungsmodelle diskutiert. Sie legen nah, daß Genus weder nur lexikalisch gespeichert ist noch ausschließlich auf der Basis von Regeln zugewiesen wird. Es wird angenommen, daß beide Strategien Teil der sprachlichen Kompetenz sind. / Different rules have been proposed for the assignment of gender to nouns in German. For instance, on the basis of derivational or diminutive suffixes gender can be assigned reliably, with only a few exceptions. However, there are several nouns that do not have any formal indication of gender. It was the aim to investigated whether normal and aphasic speakers benefit from formal gender cues. Results indicate that healthy speakers do not profit from gender cues in a gender assignment task. There are no differences in reaction times between the transparent and nontransparent condition. This contradicts findings from languages like French and Italian. However, Broca's and Wernicke's aphasics benefit from gender cues, although they do so in a different way. I interpret these findings within the context of current models of language processing and argue that gender is neither only lexically stored nor exclusively assigned on the basis of assignment rules. Both strategies seem to be part of German speakers' language competence.