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Biomedical subjects

F Müller-Spahn

Publications and source records attributed to F Müller-Spahn.

At least 19 recordsLinked to original sources
PubMed2006

Apolipoprotein E epsilon 4 is associated with an increased vulnerability to cell death in Alzheimer's disease.

The presumption to suffer from Alzheimer's disease (AD) accelerates with aging. One important risk factor seems to be the isoform epsilon 4 of the apolipoprotein E gene (Apo epsilon 4), which increases the risk to develop AD at an earlier age. Furthermore, convincing evidence is provided that apoptotic cell death mechanisms play an important role in neuronal cell death in AD. In the present study, we investigated whether abnormalities in apoptosis and caspase-3 activity can be found at the level of lymphocytes and a T cell subtype, CD4 T cells, from AD patients compared to aged sex- and ApoE genotype-matched non-demented controls. Under different experimental conditions (at baseline or after in vitro incubation in the presence of proapoptotic stimuli) increased levels of apoptosis and enhanced caspase-3 activity were detected in lymphocytes from AD patients. This difference was most pronounced in the CD4(+) T cell subtype. Notably, we found a significant increase of apoptotic cells and caspase-3 activity in lymphocytes from AD patients bearing one or two alleles of the ApoE4 compared to non-E4 carriers. Again, these effects were strongest in CD4(+) T cells. Circulating amyloid-beta (A beta) levels did not differ between AD patients bearing ApoE4 and non-ApoE4 and age-matched controls. Therefore, it is likely that circulating A beta is not responsible for the observed effects, which might rather reflect an ongoing systemic response in AD, e.g. an increase in CD95 expression.

Aged↗
PubMed2006

Obsessive-compulsive disorder due to neuroacanthocytosis treated with citalopram. A case report.

Neuroacanthocytois is a rare hereditary disease, which causes a degeneration of the striatum. Patients develop a choreatic movement disorder and also complex psychiatric symptoms, such as psychosis or Tourette's syndrome. We report a case of obsessive-compulsive disorder due to neuroacanthocytosis. The striatum plays an important role in the pathophysiology of obsessive-compulsive disorder. In Huntington's disease we also find obsessive-compulsive disorders, due to impairment of the fronto-striatal loop. Encouraged by similar pathophysiology and promising reports of selective serotonin reuptake inhibitors in this disease, we started a treatment with citalopram to which the patient responded very well.

Adult↗
PubMed2005

[Diagnosis and therapy of paranoid syndromes in the elderly].

Paranoid syndromes in the elderly are nosologically unspecific. Delusional disorder is characterized by the presence of delusions, typically persecutory, commonly in their homes. Frequent risk factors are discriminating, insulting or threatening life events, social isolation as well as sensory impairments. Atypical antipsychotics are considered as first line treatment. Delusion of parasitosis and erotomania are presented as subtypes of delusional disorders.

Aged↗
PubMed2004

Auditory distraction in young and middle-aged adults: a behavioural and event-related potential study.

Cognitive tasks involving distraction are associated with an early age-related decline in performance. Involuntary shifts in attention to irrelevant stimulus features and subsequent reorientation were studied in young and middle-aged subjects focussing on behavioural and event-related potential (ERP) measures. Subjects were asked to discriminate between equiprobable short and long auditory stimuli. Irrelevant rare frequency deviations prolonged reaction times (RT's), while an age-related effect on RT's was not observed. In contrast, notably after short deviant tones the error rate was considerably increased in the middle-aged subjects. ERP measures after deviant stimuli elicited a sequence of mismatch negativity (MMN), P3a and reorienting negativity (RON). The latency and amplitude of the MMN did not differ between age groups indicating an unchanged deviance detection. However, the consecutive process of attention orientation (P3a) was delayed and the subsequent reorienting (RON) to the primary task was strongly attenuated in the middle-aged subjects. After short deviants the RON was virtually absent in the middle-aged subjects, which might account for the observed decline of accuracy.

Acoustic Stimulation↗
PubMed2003

[Treatment of acrophobia in a virtual environment].

Specific phobias are one of the most frequent mental health problems and can lead to years of personal suffering. The most effective treatment is exposure therapy. Our aim was to proof the feasibility and efficacy of virtual environments in treating acrophobia patients using a manually guided exposure therapy. Our pilot study was designed as a crossover intervention with a waiting list condition as a control group. After treatment, our results show that exposure in virtual environments is a feasible technique, can provoke anxiety, and leads to a therapeutic effect.

Adult↗
PubMed2003

Beta-amyloid modulates tyrosine kinase B receptor expression in SHSY5Y neuroblastoma cells: influence of the antioxidant melatonin.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in humans and is characterized by neuronal loss, neurofibrillary tangles and beta-amyloid deposition. The interaction between neurotrophins and their tyrosine kinase (trk) receptors is important for cellular differentiation and survival. Interestingly, marked reductions in neurotrophins and receptors have been reported in AD. The cause of the decrease in these molecules remains unclear. However, the role of beta-amyloid (A beta) appears central in understanding the mechanisms controlling neurotrophin/trk expression. In this study we exposed SHSY5Y neuroblastoma cells to A beta or hydrogen peroxide and measured the expression of trk B/truncated trk B, and brain-derived neurotrophic factor (BDNF)/NT4 at the protein and molecular level. We show that A beta or hydrogen peroxide (H(2)O(2)) induces oxidative stress and cell cytotoxicity. The exposure of cells to A beta results in an increased trk B expression with a concurrent reduction in truncated trk B levels. H(2)O(2) exposure decreased both trk B and truncated trk B levels at the cell surface. At the molecular level trk B RNA increased in the presence of A beta and was unaffected by H(2)O(2). Similarly, BDNF and NT4 levels increased in the presence of A beta. Pre-treatment of cells with the anti-oxidant melatonin returns trk receptor expression, mRNA and BDNF/NT4 secretion to normal levels. These results are significant as they can help in the planning and implementation of AD treatment strategies involving neurotrophins.

Alzheimer Disease↗
PubMed2003

Is interval medication a successful treatment regimen for schizophrenic patients with critical attitudes towards treatment?

In neuroleptic long-term medication, only part of the patients accept regular intake of neuroleptic drugs. The question is whether an interval medication regimen as opposed to continuous medication can help to reduce drop outs in patients with critical attitudes towards long-term medication. In a 2-year prospective study, 122 patients were randomised to an interval and 164 to a continuous neuroleptic medication regimen. The drop out rates were 62.5% in the interval and 53.7% in the continuous medication group. Drop outs generally show more negative attitudes towards treatment. Patients with negative attitudes do not do better under interval medication. Moreover, this regimen even requires more cooperation and trust in terms of the necessity of medication on the part of the patient compared to the continuous medication regimen. Interval medication therefore is a strategy which can only be successful in highly cooperative, but not in treatment-reluctant patients.

Antipsychotic Agents↗
PubMed2002

Frontocortical N-acetylaspartate reduction associated with long-term i.v. heroin use.

To examine possible metabolic frontal lobe alterations in i.v. heroin-dependent patients with different histories of concomitant substance use, N-acetylaspartate (NAA), a putative marker of neuronal viability, was measured by (1)H-MRS. Compared with controls, NAA levels in patients were reduced by 7% in gray matter (p = 0.015) but not in white matter. To what extent comorbid conditions or substance use, including alcohol, contributed to these frontocortical metabolic changes remains to be elucidated.

Adult↗
PubMed2002

Intravenous antidepressant treatment: focus on citalopram.

During the last decade, the number of patients who consult primary care physicians or psychiatrists for symptoms of depression has doubled. The majority of depressed patients are prescribed oral medication; however, in several European countries antidepressant therapy may be initiated with a daily intravenous infusion. The choice of intravenous antidepressants was previously limited to agents such as dibenzepine, doxepin, clomipramine and viloxazine. More recently, the selective serotonin reuptake inhibitor (SSRI) citalopram has been administered as an intravenous infusion to severely depressed patients. The results from both open and double-blind clinical studies with intravenous citalopram suggest that it is an effective and well-tolerated treatment for depression. Moreover, when treatment is initiated by infusion and continued orally, citalopram is at least as effective as clomipramine, doxepin and viloxazine. As with oral treatment, adverse events experienced by patients are mild to moderate in severity with 50 % of patients reporting no adverse events. The high bioavailability of citalopram indicates that the switch from intravenous to oral citalopram would prevent a deterioration of symptoms as plasma drug concentrations would be maintained. Thus citalopram, the only SSRI available as an intravenous formulation, may be a useful addition for the treatment of severely depressed patients who may benefit from more intensive therapy. The aim of this paper is to review available data detailing the clinical outcome of intravenously administered citalopram in depressed patients.

Administration, Oral↗
PubMed2002

The effects of beta-estradiol on SHSY5Y neuroblastoma cells during heavy metal induced oxidative stress, neurotoxicity and beta-amyloid secretion.

The role of estrogen as a neurotrophic/neuroprotective agent in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases is increasingly being shown. In this study we examine the neuroprotective effects of beta-estradiol on SHSY5Y neuroblastoma cells which have been exposed to the heavy metals cobalt and mercury. The results show that cobalt and mercury are able to induce oxidative stress and cell cytotoxicity and increase the secretion of beta-amyloid 1-40 and 1-42. These deleterious effects are reversed by the pretreatment of cells with beta-estradiol. It is further shown that beta-estradiol exerts its neuroprotective action through mechanisms which reduce oxidative stress and reduce beta-amyloid secretion. Pre-treatment of the cells with alpha-estradiol did not alleviate the toxic effects of the heavy metals. Our results are significant as they contribute to a better understanding of the mode of action of estrogen with relevance to its use in the treatment of neurodegenerative disorders.

Amyloid beta-Peptides↗
PubMed2002

Oxidative stress modulates tyrosine kinase receptor A and p75 receptor (low-affinity nerve growth factor receptor) expression in SHSY5Y neuroblastoma cells.

The interaction of neurotrophins and their tyrosine kinase receptors (trks) is essential for differentiation and survival of brain cells. In Alzheimer's disease (AD), the number of neurotrophins and receptors is markedly decreased. The cause of this reduction is unclear, but the role of beta-amyloid (Abeta) seems central in understanding the mechanisms controlling neurotrophin and trk expression. In the study reported here, we exposed SHSY5Y neuroblastoma cells to Abeta or hydrogen peroxide (H(2)O(2)) and measured the expression of trk-A and p75 at the protein and molecular levels. Both Abeta and H(2)O(2) induced oxidative stress (measured by a decrease in cellular glutathione), which decreased trk-A levels and increased p75 levels, decreased messenger RNA (mRNA) levels of both receptors, and increased nerve growth factor (NGF) secretion. Pretreatment of cells with the antioxidant melatonin returned levels of protein expression, mRNA, and NGF secretion to normal. These results are significant, as they can help in the planning and implementation of AD treatment strategies involving neurotrophins.

Amyloid beta-Peptides↗
PubMed2001

Hippocampal estrogen beta-receptor immunoreactivity is increased in Alzheimer's disease.

Post-menopausal estrogen use reduces the risk and severity of Alzheimer's disease (AD). The present study investigates the distribution of both estrogen receptors ER alpha and ER beta in the human hippocampus in aged controls and in AD cases with immunohistochemistry. No ER alpha immunoreactivity was observed both in controls and in AD cases. On the other hand, ER beta was observed in some neuronal cells in the hippocampal subfields CA1--4, in astrocytes and in extracellular deposits both in controls and AD cases. The ER beta immunoreactivity was distinctly increased in all AD cases in cellular and extracellular localizations indicating a role for ER beta-mediated estrogen effects in AD-related neuropathology. This study provides the first demonstration of ER beta in human hippocampus in aged controls compared to AD cases.

Aged↗
PubMed2001

Cerebrovascular melatonin MT1-receptor alterations in patients with Alzheimer's disease.

The pineal hormone melatonin has two major functions: as a transducer of the circadian day-night signal across the seasons, and as a vasoactive substance regulating cerebral circulation. The vasoconstrictive effects of melatonin have been postulated to be mediated by the melatonin 1a-receptor (MT1). The objective of this study was to provide the first immunohistochemical evidence for the localization of vascular MT1 in human control hippocampus compared to Alzheimer's disease (AD) patients, since regional blood flow impairments contribute to the neurodegenerative course of the disease. Both superficial and intrahippocampal arteries revealed MT1 immunoreactivity in adventitia in controls, which was distinctly increased in AD patients. The increased MT1 in AD may indicate a regulatory response to impaired melatonin levels in those patients, contributing to the regulation of cerebral circulation.

Aged↗
PubMed2001

Melatonin protects SHSY5Y neuroblastoma cells from cobalt-induced oxidative stress, neurotoxicity and increased beta-amyloid secretion.

Heavy metals are increasingly being implicated as causative agents in neurodegenerative diseases such as Alzheimer's disease (AD). Cobalt, a positively charged transition metal, has previously been shown to be in elevated levels in the brain of AD patients compared with age-matched controls. In this study, we investigate the effects of cobalt as an inducer of oxidative stress/cell cytotoxicity and the resultant metabolic implications for neural cells. We show that cobalt is able to induce cell cytotoxicity (reduced MTT metabolism) and oxidative stress (reduced cellular glutathione). The pre-treatment of cells with the pineal indoleamine melatonin, prevented cell cytotoxicity and the induction of oxidative stress. Cobalt treatment of SHSY5Y cells increased the release of beta-amyloid (Abeta) compared with untreated controls (ratio Abeta 40/42). Melatonin pre-treatment reversed the deleterious effects of cobalt. These findings are significant as cobalt is an essential nutritional requirement, usually bound to cobalamin (vitamin B12), for all animals which in the unbound form could lead to neurotoxicity.

Alzheimer Disease↗
PubMed2001

N-acetyl-L-cysteine protects SHSY5Y neuroblastoma cells from oxidative stress and cell cytotoxicity: effects on beta-amyloid secretion and tau phosphorylation.

Redox changes within neurones are increasingly being implicated as an important causative agent in brain ageing and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). Cells have developed a number of defensive mechanisms to maintain intracellular redox homeostasis, including the glutathione (GSH) system and antioxidant enzymes. Here we examine the effects of N-acetyl-L-cysteine (NAC) on beta-amyloid (A beta) secretion and tau phosphorylation in SHSY5Y neuroblastoma cells after exposure to oxidative stress inducing/cytotoxic compounds (H(2)O(2), UV light and toxic A beta peptides). A beta and tau protein are hallmark molecules in the pathology of AD while the stress factors are implicated in the aetiology of AD. The results show that H(2)O(2), UV light, A beta 1-42 and toxic A beta 25-35, but not the inactive A beta 35-25, produce a significant induction of oxidative stress and cell cytotoxicity. The effects are reversed when cells are pre-treated with 30 mM NAC. Cells exposed to H(2)O(2), UV light and A beta 25-35, but not A beta 35-25, secrete significantly higher amounts of A beta 1-40 and A beta 1-42 into the culture medium. NAC pre-treatment increased the release of A beta 1-40 compared with controls and potentiated the release of both A beta 1-40 and A beta 1-42 in A beta 25-35-treated cells. Tau phosphorylation was markedly reduced by H(2)O(2) and UV light but increased by A beta 25-35. NAC strongly lowered phospho-tau levels in the presence or absence of stress treatment.

Acetylcysteine↗
PubMed2001

A prospective study of factors influencing adherence to a continuous neuroleptic treatment program in schizophrenia patients during 2 years.

Dropout from prophylactic neuroleptic treatment is one major reason for relapse in schizophrenia patients. There is a lack of prospective studies on factors that predict medication adherence. We investigated factors suspected to predict dropout from continuous neuroleptic treatment in a 2-year prospective study involving 122 outpatients with a DSM-III-R diagnosis of schizophrenia. Forty-two (34.4%) were classified as patient-related dropouts. No significant difference between compliant patients and dropouts was found with regard to sociodemographic variables, except that compliant patients were significantly older. Also, no differences in psychopathology were seen at the beginning of treatment, but compliant patients had a longer duration of illness. Compliant patients had higher doses of neuroleptics in the initial stabilization phase and correspondingly showed more extrapyramidal signs. Physicians rated compliant patients from the beginning as more cooperative. These patients also showed significantly higher scores in positive treatment expectations. In a stepwise regression analysis, positive illness concepts, the global assessment of functioning (GAF), and the physicians' view of patients' cooperation predicted 19 percent of the variance. We concluded that the prediction of dropouts is insufficient and remains largely an unsolved problem. Future research should focus more on context factors in the search for clinically meaningful explanations of patient dropout from treatment.

Adult↗
PubMed2000

[Diagnosis and therapy of behavior disorders in dementia].

Alzheimer's disease is one of the most common brain disorder in the elderly. In most patients who develop dementia the core syndrome of cognitive dysfunction is superimposed over the course of the disease by behavioral disorders that manifest at least temporarily to varying degrees. These include depression, anxiety, agitation, restlessness, aggression, disturbances of the sleep-wake cycle, delusions and hallucinations. Classical psychiatric exploration can be complemented by the use of the Neuropsychiatric Inventory (NPI) which allows structured diagnosis and comparative documentation of the clinical course. The majority of psychotropic drugs used in psychogeriatics have not been specifically developed for or tested in elderly, often multimorbid patients. Substances used in psychogeriatrics are subject to special requirements due to the pharmacokinetic and pharmacodynamic changes specific to very old persons. They must show clinical efficacy and a low rate of cardiovascular, peripheral and central anticholinergic effects, a low delirogenic potential and favorable pharmacokinetic and pharmacodynamic properties. Most of the newer atypical neuroleptics (e.g. risperidone) and the newer antidepressants (e.g. from the class of selective serotonin reuptake inhibitors, SSRIs, or selective serotonin and noradrenaline reuptake inhibitors, SNRIs) tend to fulfill these criteria better than the high-potency neuroleptics of the butyrophene type (e.g. haloperidol) or the tricyclic antidepressants. For that reason, these newer products should usually be preferred over the conventional agents.

Aged↗