Tanja Maria Michel

University of Rostock, Rostock, Mecklenburg-Vorpommern, Germany

Are you Tanja Maria Michel?

Claim your profile

Publications (21)61.92 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Obsessive-compulsive symptoms (OCS) constitute a major comorbidity in schizophrenia. Prevalence estimations of OCS for patients with at-risk mental states (ARMS) for psychosis vary largely. It is unclear how ARMS patients with or without comorbid OCS differ regarding general psychosocial functioning, psychotic and affective symptoms and neurocognitive abilities. At-risk mental states patients (n = 233) from the interventional trial PREVENT (Secondary Prevention of Schizophrenia) were stratified according to the presence or absence of comorbid OCS and compared on several clinical variables. Patients, who fulfilled the criteria for obsessive-compulsive disorder (OCD) or presented with subclinical OCS (ARMSposOCS sample), did not significantly differ from patients without OCS (ARMSnegOCS) with regard to gender, age, premorbid verbal intelligence and levels of education. Furthermore, similar severity of depressive syndromes, basic cognitive, attenuated psychotic and brief limited intermittent psychotic symptoms were found. However, ARMSposOCS patients showed more impairment of psychosocial functioning and higher general psychopathology. In contrast, they scored higher in cognitive tasks measuring working memory and immediate verbal memory. Findings extend upon previous results due to the multidimensional assessment. Subsequent longitudinal studies might elucidate how comorbid OCS influence differential treatment response, especially to cognitive behavioural interventions and the transition rates to psychosis.
    Acta Psychiatrica Scandinavica 02/2014; · 4.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aldehyde dehydrogenases (ALDH) play a key role in neuronal protection. They exert this function by metabolizing biogenic amine-related aldehydes, e.g. 3,4-dihydroxyphenylacetaldehyde (DOPAL), and by protecting neurons against aldehyde- and oxidative stress-related neurotoxicity. The role of these different isoenzymes has been discussed in other neurodegenerative disorders before. It is somewhat surprising that only few studies have investigated their role in the aetiology of Parkinson's disease (PD), in both the degeneration of dopaminergic neurons and the formation of Lewy bodies. Earlier studies report severe alterations of the cytosolic isoform of ALDH expression (ALDH 1A1) in the substantia nigra of patients with PD. However, there are no data regarding the activity of ALDH 2 located at the inner mitochondrial membrane. Since mitochondrial dysfunctions are hypothesized to be of importance in the aetiology of PD we have examined the enzymatic activity of mitochondrial ALDH 2 in post-mortem putamen and frontal cortex of patients with PD and controls. We found that mitochondrial ALDH 2 activity in contrast to the frontal cortex was significantly increased in the putamen of patients with PD compared to controls.
    Parkinsonism & Related Disorders 01/2014; 20S1:S68-S72. · 3.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Autism spectrum disorders (ASDs) are increasing in incidence but have an incompletely understood etiology. Tools for uncovering clues to the cause of ASDs and means for diagnoses are valuable to the field. Mass Spectrometry (MS) has been a useful method for evaluating differences between individuals with ASDs versus matched controls. Different biological substances can be evaluated using MS, including urine, blood, saliva, and hair. This technique has been used to evaluate relatively unsupported hypotheses based on introduction of exogenous factors, such as opiate and heavy metal excretion theories of ASDs. MS has also been used to support disturbances in serotonin-related molecules, which have been more consistently observed in ASDs. Serotonergic system markers, markers for oxidative stress, cholesterol system disturbances, peptide hypo-phosphorylation and methylation have been measured using MS in ASDs, although further analyses with larger numbers of subjects are needed (as well as consideration of behavioral data). Refinements in MS and data analysis are ongoing, allowing for the possibility that future studies examining body fluids and specimens from ASD subjects could continue to yield novel insights. This review summarizes MS investigations that have been conducted to study ASD to date and provides insight into future promising applications for this technique, with focus on proteomic studies.
    Journal of Molecular Psychiatry. 05/2013;
  • Tanja Maria Michel, Dietrich Pülschen, Johannes Thome
    [Show abstract] [Hide abstract]
    ABSTRACT: Studies of the World Health Organization suggest that in the year 2020, depressive disorder will be the illness with the highest burden of disease. Especially unipolar depression is the psychiatric disorder with the highest prevalence and incidence, it is cost-intensive and has a relatively high morbidity. Lately, the biological process involved in the aetiology of depression has been in the focus of research. Since its emergence, the monoamine hypothesis has been adjusted and extended considerably. An increasing body of evidence points to alterations not only in brain function, but also in neuronal plasticity. The clinical presentations demonstrate these dysfunctions by accompanying cognitive symptoms such as problems with memory and concentration. Modern imaging techniques show e.g. volume reduction of the hippocampus and the frontal cortex. These findings are in line with post-mortem studies of patients with depressive disorder and they point to a significant decrease of neuronal and glial cells in cortico-limbic regions which can be seen as a consequence of alterations in neuronal plasticity in this disorder. This could be triggered by an increase of free radicals which in its turn eventually leads to cell death and consequently atrophy of vulnerable neuronal and glial cell population in these regions. Therefore, research on increased oxidative stress in unipolar depressive disorder, mediated by elevated concentrations of free radicals, has been undertaken. This review gives a comprehensive overview over the current literature discussing the involvement of oxidative stress and free radicals in depression. Methods: medline search "oxidative stress depression", "oxidative stress affective disorders", "free radicals and depression", "free radicals and affective disorders" "antidepressants oxidative stress" "antidepressants and free radicals". We found numerous reports elaborating on depressive disorder and oxidative stress. Most of the previous studies concentrated on investigating antioxidants in human blood as well as in animal models. However, few of these reports were able to show correlations of reduced oxidative stress with antidepressant treatment and clinical outcome measures. Fewer studies elaborated on the concentrations of antioxidants in the human brain and some on pro-oxidative enzymes in depression. However, more studies are needed to elucidate the complex role of oxidative stress in the aetiology of depression.
    Current pharmaceutical design 06/2012; · 4.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Antipsychotics, cognitive behavioral therapy (CBT), and omega-3-fatty acids have been found superior to control conditions as regards prevention of psychosis in people at-risk of first-episode psychosis. However, no large-scale trial evaluating the differential efficacy of CBT and antipsychotics has been performed yet. In PREVENT, we evaluate CBT, aripiprazole, and clinical management (CM) as well as placebo and CM for the prevention of psychosis in a randomized, double-blind, placebo-controlled trial with regard to the antipsychotic intervention and a randomized controlled trial with regard to the CBT intervention with blinded ratings. The hypotheses are first that CBT and aripiprazole and CM are superior to placebo and CM and second that CBT is not inferior to aripiprazole and CM combined. The primary outcome is transition to psychosis. By November 2010, 156 patients were recruited into the trial. The subjects were substantially functionally compromised (Social and Occupational Functioning Assessment Scale mean score 52.5) and 78.3% presented with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition axis I comorbid diagnosis. Prior to randomization, 51.5% of the participants preferred to be randomized into the CBT arm, whereas only 12.9% preferred pharmacological treatment. First, assessments of audiotaped treatment sessions confirmed the application of CBT-specific skills in the CBT condition and the absence of those in CM. The overall quality rating of the CBT techniques applied in the CBT condition was good. When the final results of the trial are available, PREVENT will substantially expand the current limited evidence base for best clinical practice in people at-risk (prodromal) of first-episode psychosis.
    Schizophrenia Bulletin 09/2011; 37 Suppl 2:S111-21. · 8.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Autism spectrum disorders (ASD) are pervasive developmental disorders with characteristic core symptoms such as impairments in social interaction, deviance in communication, repetitive and stereotyped behavior, and impaired motor skills. Anomalies of brain structure have repeatedly been hypothesized to play a major role in the etiopathogenesis of the disorder. Our objective was to perform unbiased meta-analysis on brain structure changes as reported in the current ASD literature. We thus conducted a comprehensive search for morphometric studies by Pubmed query and literature review. We used a revised version of the activation likelihood estimation (ALE) approach for coordinate-based meta-analysis of neuroimaging results. Probabilistic cytoarchitectonic maps were applied to compare the localization of the obtained significant effects to histological areas. Each of the significant ALE clusters was analyzed separately for age effects on gray and white matter density changes. We found six significant clusters of convergence indicating disturbances in the brain structure of ASD patients, including the lateral occipital lobe, the pericentral region, the medial temporal lobe, the basal ganglia, and proximate to the right parietal operculum. Our study provides the first quantitative summary of brain structure changes reported in literature on autism spectrum disorders. In contrast to the rather small sample sizes of the original studies, our meta-analysis encompasses data of 277 ASD patients and 303 healthy controls. This unbiased summary provided evidence for consistent structural abnormalities in spite of heterogeneous diagnostic criteria and voxel-based morphometry (VBM) methodology, but also hinted at a dependency of VBM findings on the age of the patients.
    Human Brain Mapping 06/2011; 33(6):1470-89. · 6.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mounting evidence shows that oxidative stress (OS) and the purine/adenosine system play a key role in the pathophysiology of schizophrenia. Lately, our group pointed out that not only antioxidants, but also the prooxidant system plays an important role in neuro-psychiatric disorders. Xanthine oxidase (XO) is an enzyme of special interest in this context, since it acts as a prooxidant, but its main product is a vastly important antioxidant, uric acid (UA). Furthermore, XO plays major part in the purine/adenosine metabolism, which has been hypothesised to play a role in schizophrenia as well. We examined the activity of XO in the striato-cortico-limbic system of schizophrenic patients (SP) and controls using a commercially available activity assay. We found decreased activity of XO in the occipital cortex and thalamus of patients with psychosis. Furthermore, XO shows a significant positive correlation with chlorpromazine equivalents in the putamen and the temporal cortex. Nevertheless, our results might suggest a downregulation of cellular defence mechanisms in schizophrenia in several brain regions, which could account for neuronal alterations which have been described before. This demonstrates that more research is needed to fully understand the role of the complex enzyme XO in the pathophysiology of schizophrenia.
    The World Journal of Biological Psychiatry 11/2010; 12(8):588-97. · 3.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Oxidative stress (OS), is defined as an imbalance of pro- and antioxidants, leading to increased production of free radicals, which can lead to cell damage and death, has been postulated as important factors in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Most research has concentrated on the antioxidant system, for the first time, this proof of concept study examines the prooxidant system by investigating kinetic parameters of the free radical producing enzyme xanthine oxidase directly in post mortem brain tissue. We determined the Michaelis-Menten constant (K(M)) and the maximal velocity (V(Max)) of xanthine oxidase (XO) in the cortico-limbic system of patients with AD using activity assays. We found the Michaelis-Menton constant of XO significantly decreased in hippocampus of patients with AD compared to controls. None of the other brain regions showed any significant alterations of these parameters. These results add further evidence to the amount of research indicating that OS plays an important role in AD. Moreover, these results should encourage more research in this field and it maybe speculated that this might open new avenues for treatment and prevention in AD.
    The World Journal of Biological Psychiatry 04/2010; 11(4):677-81. · 3.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A growing body of literature suggests persistent and selective structural changes in the cortico-limbic-thalamic-striatal system in patients with recurrent depressive disorder (DD). Oxidative stress is thought to play a key role in these processes. So far, the main scientific focus has been on antioxidant enzymes in this context. For the first time, this proof of concept study examines the activity of the free radicals producing the enzyme, xanthine oxidase (XO), directly in the cortico-limbic-thalamic-striatal system of patients with recurrent depression. The activity of XO was ascertained in the cortico-limbic-thalamic-striatal regions in post-mortem brain tissue of patients with recurrent depressive episodes and individuals without any neurological or psychiatric history (7/7). We measured the XO activity in following brain areas: hippocampus, regio entorhinalis, thalamus, putamen and caudate nucleus. In this study, we report a significant increase of XO activity in the thalamus and the putamen of patients with depression. Our findings contribute to the growing body of evidence suggesting that oxidative stress plays a pivotal role in certain brain areas in recurrent depressive disorder.
    The World Journal of Biological Psychiatry 01/2010; 11(2 Pt 2):314-20. · 3.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: For decades, it has been acknowledged that oxidative stress due to free radical species contributes to the pathophysiology of aging and neurodegenerative diseases. Aldehyde dehydrogenases (ALDH) not only transform aldehydes to acids but also act as antioxidant enzymes. However, little is known about the implications of the enzymatic family of ALDH in the context of neurodegenerative processes such as Alzheimer's disease (AD). We therefore examined the enzymatic activity of the mitochondrial ALDH-isoform in different regions of the postmortem brain tissue isolated from patients with AD and controls. We found that the mitochondrial ALDH activity was significantly increased only in the putamen of patients suffering from AD compared to controls. This is of particular interest since mediators of oxidative stress, such as iron, are increased in the putamen of patients with AD. This study adds to the body of evidence that suggests that oxidative stress as well as aldehyde toxicity play a role in AD.
    Journal of Alzheimer's disease: JAD 01/2010; 19(4):1295-301. · 4.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prefrontal cortical (PFC) and hippocampal (HI) volume reductions have been consistently found in patients with recurrent depressive disorder (DD). Here we examine the possibility that oxidative stress, widely implicated in neuronal cell damage, may contribute to these brain structural changes. We compared manganese (Mn) and copper/zinc (Cu/Zn) superoxide dismutase (SOD) coenzyme concentrations in postmortem PFC and hippocampal brain tissue from 7 patients with DD and 7 neuropsychiatrically healthy controls using sandwich-type enzyme-linked immunosorbent assay (ELISA) technique. The concentration of Cu/Zn-SOD was significantly increased in the PFC but not in the hippocampus of patients. There was no significant change in Mn-SOD enzyme concentration in either region. Our findings contribute to the growing body of evidence implicating oxidative stress in the pathophysiology of depressive disorder.
    Psychiatry Research 06/2007; 151(1-2):145-50. · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Near-infrared spectroscopy (NIRS) is a noninvasive optical method for in vivo measurement of regional brain tissue oxygenation. Light from the near-infrared spectrum can penetrate the skull and is mainly absorbed by oxyhaemoglobin (O(2)Hb) and desoxyhaemoglobin (HHb). From the amount of reflected near-infrared light in relation to the amount absorbed by brain tissue, regional changes in O(2)Hb and HHb concentrations can be calculated spectrophotometrically. It has been shown that NIRS is not only able to measure massive disturbances in cerebral blood circulation due to serious neurological diseases, but that it also is sensitive enough to assess task-specific patterns of activation in healthy subjects during circumscribed cognitive processes. Preliminary investigations indicate altered regional brain tissue oxygenation in psychiatric patients during cognitive activation tasks. The NIRS outmatches other functional imaging methods in that it has no side effects and is well tolerated by psychiatric patients. Furthermore, it can be applied quickly and easily. Thus, NIRS is a potential screening method in psychiatric settings, provided that robust parameters of reliable diagnostic and/or prognostic value can be developed for individual psychiatric illnesses. However, this will depend on broader application of the method combined with established neurophysiological procedures and functional imaging techniques in psychiatric research.
    Der Nervenarzt 10/2004; 75(9):911-6. · 0.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Die Nah-Infrarot-Spektroskopie (NIRS) ist eine nichtinvasive optische Methode zur Messung der regionalen Hirngewebeoxygenierung in vivo. Licht aus dem nah-infraroten Spektrum kann die Schdelkalotte durchdringen und wird im Hirngewebe hauptschlich von Oxy- (O2Hb) und Deoxyhmoglobin (HHb) absorbiert. Aus der Relation von in das Gehirn abgegebenem zu reflektiertem Nah-Infrarot-Licht kann daher spektrophotometrisch die regionale Konzentrationsnderung von O2Hb und HHb berechnet werden. Es wurde bereits gezeigt, dass NIRS nicht nur massive Hirndurchblutungsstrungen bei schweren neurologischen Erkrankungen erfassen kann, sondern dass die Methode auch ausreichend sensitiv ist, um bei gesunden Probanden aufgabenspezifische Aktivierungsmuster whrend definierter kognitiver Prozesse zu messen. Erste Untersuchungen an psychiatrischen Patienten weisen auf vernderte regionale Hirngewebsoxygenierungen im Vergleich zu Kontrollgruppen whrend kognitiver Aktivierungsaufgaben hin. NIRS hat aufgrund seiner unkomplizierten, schnellen Durchfhrung, seiner Nebenwirkunsfreiheit und der hohen Akzeptanz bei psychiatrischen Patienten eindeutige Vorteile im Vergleich zu anderen Methoden der funktionellen Bildgebung, die die Methode auch als potenzielles Screeningverfahren in der Psychiatrie attraktiv erscheinen lassen. Voraussetzung dafr ist allerdings, dass sich in Zukunft stabile und reliable NIRS-Parameter mit diagnostischem und/oder prognostischem Wert fr bestimmte psychiatrische Erkrankungen entwickeln lassen, was nur durch eine breitere Nutzung dieser Methode in der psychiatrischen Forschung in Verbindung mit bereits etablierten Methoden der Neurophysiologie und der funktionellen Bildgebung gelingen wird.Near-infrared spectroscopy (NIRS) is a noninvasive optical method for in vivo measurement of regional brain tissue oxygenation. Light from the near-infrared spectrum can penetrate the skull and is mainly absorbed by oxyhaemoglobin (O2Hb) and desoxyhaemoglobin (HHb). From the amount of reflected near-infrared light in relation to the amount absorbed by brain tissue, regional changes in O2Hb and HHb concentrations can be calculated spectrophotometrically. It has been shown that NIRS is not only able to measure massive disturbances in cerebral blood circulation due to serious neurological diseases, but that it also is sensitive enough to assess task-specific patterns of activation in healthy subjects during circumscribed cognitive processes. Preliminary investigations indicate altered regional brain tissue oxygenation in psychiatric patients during cognitive activation tasks. The NIRS outmatches other functional imaging methods in that it has no side effects and is well tolerated by psychiatric patients. Furthermore, it can be applied quickly and easily. Thus, NIRS is a potential screening method in psychiatric settings, provided that robust parameters of reliable diagnostic and/or prognostic value can be developed for individual psychiatric illnesses. However, this will depend on broader application of the method combined with established neurophysiological procedures and functional imaging techniques in psychiatric research.
    Der Nervenarzt 09/2004; 75(9):911-916. · 0.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The topic gender and personality in alcoholism is discussed on the background of a research project on clinical aspects of alcoholism at the University of Würzburg, Germany. The data of this study are presented in the context of two questions: Which personality differences are there between women and men dependent on alcohol, and is there a connection between these personality differences and features of the alcohol dependence? Additionally, we take a look at gender-related differences in the development of alcoholism. In a first step, gender differences in the development and the course of alcoholism are investigated. The data revealed only weak differences between female and male alcoholics when important confounding variables like age and education are taken into consideration. Secondly, the female and male alcoholics are matched according to age and education and their personality structures are compared by using several well-established and standardized self-report questionnaires. No serious gender differences concerning the main characteristics of alcohol dependence could be discovered. However, some remarkable personality differences between female and male alcoholics are found: women scored significantly higher on Neuroticism and Harm-Avoidance while men reached significantly higher scores on Venturesomeness and Sensation-Seeking. In order to detect a possible connection between alcoholism and gender-related personality differences, both males and females are subdivided into two groups using the scores of Neuroticism, Harm-Avoidance, Venturesomeness and Sensation-Seeking, respectively. We have found no indication for a gender-specific relevance of personality differences between female and male alcoholics with regard to Harm-Avoidance, Venturesomeness or Sensation-Seeking. However, differences in Neuroticism have revealed a greater relevance in alcohol-dependent women than in men.
    Archives of Women s Mental Health 12/2003; 6(4):245-52. · 2.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Disturbed neural development has been postulated as a crucial factor in the pathophysiology of schizophrenic psychoses. The neurobiochemical basis for such changes of cytoarchitecture and changed neural plasticity could involve an alteration in the regulation of neurotrophic factors. In order to test this hypothesis, BDNF and NT-3 levels in post-mortem brain tissue from schizophrenic patients were determined by ELISA. There was a significant increase in BDNF concentrations in cortical areas and a significant decrease of this neurotrophin in hippocampus of patients when compared with controls. NT-3 concentrations of frontal and parietal cortical areas were significantly lower in patients than in controls. These findings lend further evidence to the neurotrophin hypothesis of schizophrenic psychoses which proposes that alterations in expression of neurotrophic factors could be responsible for neural maldevelopment and disturbed neural plasticity, thus being an important event in the etiopathogenesis of schizophrenic psychoses.
    Schizophrenia Research 11/2001; 52(1-2):79-86. · 4.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the present study, we investigated the levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in post-mortem brain tissue of Alzheimer's disease (AD) patients, and we observed a significant increase of BDNF concentration in hippocampus and parietal cortex of AD patients, as well as a negative correlation between NT-3 levels and age in hippocampus and putamen of control subjects, and for BDNF in frontal cortex. A defining feature of AD is the post-mortem identification of neuritic plaques and neurofibrillary tangles in the brain, however, a more significant neuropathological finding is the degeneration of cholinergic neurones of the basal forebrain, critically involved in memory and cognition. Neurotrophic factors are partly responsible for the maintenance of neuronal function and structural integrity in the adult brain. Our results provide, therefore, evidence that, under conditions of progressive neurodegeneration the brain stimulates the over expression of certain neurotrophic factors as a possible mechanisms of compensation, and that during senescence the expression of these molecules is regulated.
    International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 01/2001; 18(8):807-813. · 2.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the present study, we investigated the levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in post-mortem brain tissue of Alzheimer's disease (AD) patients, and we observed a significant increase of BDNF concentration in hippocampus and parietal cortex of AD patients, as well as a negative correlation between NT-3 levels and age in hippocampus and putamen of control subjects, and for BDNF in frontal cortex. A defining feature of AD is the post-mortem identification of neuritic plaques and neurofibrillary tangles in the brain, however, a more significant neuropathological finding is the degeneration of cholinergic neurones of the basal forebrain, critically involved in memory and cognition. Neurotrophic factors are partly responsible for the maintenance of neuronal function and structural integrity in the adult brain. Our results provide, therefore, evidence that, under conditions of progressive neurodegeneration the brain stimulates the over expression of certain neurotrophic factors as a possible mechanisms of compensation, and that during senescence the expression of these molecules is regulated.
    International Journal of Developmental Neuroscience 01/2001; 18(8):807-13. · 2.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD) is a progressive dementia affecting a large proportion of the aging population. The histopathological changes in AD include neuronal cell death and formation of amyloid plaques and neurofibrillary tangles (NFTs) NFTs are composed of hyperphosphorylated tau protein, and senile plaques contain aggregates of the beta-peptide. There is also evidence that brain tissue in patients with AD is exposed to oxidative stress during the course of the disease. Advanced glycation endproducts (AGEs), which are formed by a non-enzymatic reaction of glucose with long-lived protein deposits, are potentially toxic to the cell, are present in brain plaques in AD, and its extracellular accumulation in AD may be caused by an accelerated oxidation of glycated proteins. The microtubuli-associated protein tau is also subject to intracellular AGE formation. AGEs participate in neuronal death causing direct (chemical) radical production: Glycated proteins produce nearly 50-fold more radicals than non-glycated proteins, and indirect (cellular) radical production: Interaction of AGEs with cells increases oxidative stress. During aging cellular defence mechanisms weaken and the damages to cell constituents accumulate leading to loss of function and finally cell death. The development of drugs for the treatment of AD remains at a very unsatisfying state. However, pharmacological approaches which break the vicious cycles of oxidative stress and neurodegeneration offer new opportunities for the treatment of AD. Theses approaches include AGE-inhibitors, antioxidants, and anti-inflammatory substances, which prevent radical production. AGE inhibitors might be able to stop formation of AGE-modified beta-amyloid deposits, antioxidants are likely to scavenge intracellular and extracellular superoxide radicals and hydrogen peroxide before these radicals damage cell constituents or activate microglia, and anti-inflammatory drugs attenuating microglial radical and cytokine production.
    European Archives of Psychiatry and Clinical Neuroscience 02/1999; 249 Suppl 3:68-73. · 3.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cell culture and animal models suggest a significant influence of ciliary neurotrophic factor (CNTF) on cholinergic neurotransmitter systems. We therefore conducted an explorative pilot study to investigate the influence of a null mutation allele of the CNTF gene on ChAT (choline acetyltransferase) and AChE (acetylcholine esterase) activities in various regions of human post mortem brain tissue. Additionally, we determined NT3 (neurotrophin 3) levels, a factor which exhibits neurotrophic properties at cholinergic neurons, and the concentration of which in these brain regions varies with CNTF genotype. Homozygous carriers of the mutation lack CNTF completely, whereas heterozygotes have a CNTF level which is about half that of non-carriers. There was a trend toward lower ChAT and AChE activity levels in the cingulate cortex in individuals homozygous or heterozygous for the mutation when compared with non-mutant individuals. Additionally, higher NT3 concentrations were found in this region, as well as in the frontal cortex and caudate nucleus. ChAT and AChE activities in the frontal cortex and caudate nucleus were not significantly linked to CNTF genotype. These results are, however, preliminary and need to be further explored. The individuals investigated were heterogenous with respect to a range of parameters; nevertheless, the hypothesis that genetic variants for neurotrophic factors play a role in diseases of neural development and plasticity deserves further examination.
    Journal für Hirnforschung 02/1997; 38(4):443-51.
  • Biological Psychiatry - BIOL PSYCHIAT. 01/1997; 42(1).

Publication Stats

508 Citations
61.92 Total Impact Points

Institutions

  • 2012–2014
    • University of Rostock
      • Klinik und Poliklinik für Psychiatrie und Psychotherapie
      Rostock, Mecklenburg-Vorpommern, Germany
  • 2010–2014
    • RWTH Aachen University
      • Department of Psychiatry, Psychotherapy and Psychosomatics
      Aachen, North Rhine-Westphalia, Germany
  • 1997–2010
    • University of Wuerzburg
      • Department of Psychiatry, Psychosomatics, and Psychotherapy
      Würzburg, Bavaria, Germany