Biomedical subjects

J Marksteiner

Publications and source records attributed to J Marksteiner.

At least 19 recordsLinked to original sources

PubMed2007

[Differences between men and women in side effects of second-generation antipsychotics].

In this review we investigate whether sex differences exist for side effects of second-generation antipsychotics. Results are based on a MEDLINE search for the years 1974 through 2005. Even if pharmacokinetics differ between females and males, significantly higher plasma levels for women have been demonstrated only for olanzapine and clozapine. Hyperprolactinaemia is mainly induced by treatment with risperidone and amisulpride, and there is evidence for more pronounced prolactin levels in females. Most studies reviewed indicate that clozapine and olanzapine are associated with more body weight gain, once more especially in female patients. Furthermore, the few published studies indicate that metabolic syndrome is more frequent in females and there are likely no gender-specific differences between the new antipsychotic medications concerning frequency and degree of acute or chronic movement disturbance. The risk of QT prolongation with torsades de pointes arrhythmia is again higher in females. In conclusion, there is some evidence of sex differences in the side effects of second-generation antipsychotics. For better understanding of the basic mechanisms in sex differences, future studies with a primary focus on this topic are required. More specific data will help to determine how these differences shall affect clinical management.

Antidepressive Agents, Second-Generation↗

PubMed2006

Effects of age and mild cognitive impairment on direct and indirect access to arithmetic knowledge.

The present study aimed at investigating age-related changes and mild cognitive impairment (MCI) related effects in simple arithmetic. To pursue this goal, MCI patients, healthy old adults and young adults performed three computerised tasks. The production (e.g., 3 x 4=?) and the verification task (3 x 4 12?) evaluated direct access to multiplication knowledge, the number-matching task (3 x 4 34?, 'do 3 x 4 and 34 have the same digits?') tested indirect access. In verification and number-matching, interference from related distractors (e.g., 3 x 4 followed by 16) relative to unrelated distractors (17) reflects access to stored fact representations as well as efficiency of inhibition processes. Results indicated that, compared to young adults, MCI and healthy old adults were slower in responding across tasks. In production and verification, analyses of individual latency regression slopes and intercepts suggested that these age effects were related to differences at peripheral processing stages (e.g., encoding) rather than at the central (arithmetic retrieval) stage. Differences between MCI and healthy elderly emerged only in the number-matching task. While in verification effects were comparable between groups, in number-matching MCI patients were more susceptible to interference from irrelevant information than healthy old participants. Overall, the present findings indicate that aging has a general effect on peripheral processing speed, but not on arithmetic memory retrieval. Parietal cortico-subcortical circuits mediating arithmetic fact retrieval (Dehaene, S., & Cohen, L. (1995). Towards an anatomical and functional model of number processing. Mathematical Cognition, 1, 83-120; Dehaene, S., & Cohen, L. (1997). Cerebral pathways for calculation: Double dissociation between rote verbal and quantitative knowledge of arithmetic. Cortex, 33, 219-250) thus seem to be preserved in normal aging and MCI. In contrast, MCI patients show enhanced interference in number-matching. This task-specific lack of inhibition may point to dysfunctional frontal cortico-subcortical networks in MCI.

Adult↗

PubMed2006

First localization and biochemical identification of chromogranin B- and secretoneurin-like immunoreactivity in the fetal human vagal/nucleus solitary complex.

The human vagal/nucleus solitary complex is a primary visceral relay station and an integrative brain stem area which displays a high density of chromogranin B- and secretoneurin-like immunoreactivity. In this study, we localized and biochemically identified these proteins during prenatal development. At prenatal week 11, 15, 20 and 37, we performed a chromatographic analysis to identify the molecular forms of PE-11, a peptide within the chromogranin B sequence, and secretoneurin, a peptide within secretogranin II. Their localization was studied with immunocytochemistry, and was compared to that of substance P which is well established as a functional neuropeptide in the vagal/nucleus solitary complex. At prenatal week 11, chromogranin B-, secretoneurin- and substance P-like immunoreactivities were detected consisting of varicosities, varicose fibers and single cells. At the same time, PE-11 and secretoneurin appeared as a single peak in chromatographic analysis. Prohormone convertases PC1- and PC2-like immunoreactivities were also present at week 11. In general, the density for each peptide increased during later fetal stages with the highest density at week 37. These results demonstrate that each chromogranin peptide is expressed during human fetal life in neurons of the vagal/nucleus solitary complex indicating that these peptides could be important during prenatal development.

Chromogranin B↗

PubMed2005

[Gender differences in cognitive functions].

Gender differences in neuropsychological functioning of patients with psychiatric disorders have been studied extensively in the last years. The available studies provide conflicting results, which can be attributed to the complexity of variables influencing cognitive sex differences. In this article we review the literature about gender differences in cognitive functions in healthy men and women and discuss the relevance of hormones, socio-cultural factors, educational factors and training on the occurrence of these sex differences. Furthermore we summarize the results from functional MRI experiments, which is a useful tool for noninvasively localizing areas in the brain involved in specific cognitive functions.

Brain↗

PubMed2004

Subacute dementia and imaging correlates in a case of Fahr's disease.

We report a case of idiopathic bilateral basal ganglia calcinosis, or Fahr's disease (FD) in a 50 year old patient who developed rapidly progressive behavioural abnormalities and severe neuropsychological impairments, but no movement disorder. Neuropsychological deficits included a severe dysexecutive syndrome, anterograde amnesia, and attentional impairment. Neuropsychiatric features comprised apathy with intermittent disinhibition, anxiety, irritability, frequent mood changes, ritualistic and antisocial behaviour, and psychosis. Fluorodeoxyglucose positron emission tomography showed a massive reduction of glucose metabolism in the basal ganglia and the frontal brain. The observed abnormalities possibly result from a disruption of frontostriatal circuits, presumably at the basal ganglia level. This case indicates that FD may cause exclusively behavioural alterations and that the associated hypometabolism in certain frontal areas is closely related to the clinical picture.

Aggression↗

PubMed2003

Distribution of catestatin-like immunoreactivity in the human auditory system.

Chromogranin A (CgA) belongs to the family of chromogranin peptides which are contained in large dense-core vesicles. The novel CgA fragment catestatin (bovine CgA(344-364); RSMRLSFRARGYGFRGPGLQL) is a potent inhibitor of catecholamine release by acting as a nicotinic cholinergic antagonist. Catestatin is a recently characterized neuropeptide, consisting of 21 amino acids, which might play an autocrine regulatory role in neuroendocrine secretion through its interaction with different nicotinic acetylcholine receptor subtypes. This study investigates for the first time the distribution of this peptide in the human auditory system using immunohistochemistry. A high density of catestatin-like immunoreactivity (catestatin-LI) is located in the spiral ganglion cells. In the dorsal cochlear nucleus, a high density of catestatin-LI consists of varicose fibers, immunoreactive varicosities and immunoreactive neurons. A moderate density is detected in the ventral cochlear and the medial vestibular nucleus. A low density is found in the inferior colliculus and superior olivary complex. The study indicates that catestatin is distinctly distributed in the auditory system, suggesting a role as a neuromodulatory peptide. Further studies should elucidate a possible interaction with other neurotransmitters in the auditory system.

Aged↗

PubMed2003

Fluoxetine in Alzheimer's disease with severe obsessive compulsive symptoms and a low density of serotonin transporter sites.

The treatment of behavioral disturbances is particularly challenging in patients suffering from dementia. In an 80-year-old female patient with probable AD and severe obsessive and compulsive symptoms, we demonstrated a significant reduction in the density of serotonin transporter sites using 1231-beta-CIT SPECT. Treatment with fluoxetine for 6 months resulted in significant symptom relief and an increasing density of serotonin transporter sites when compared to the beginning of treatment. Therefore, this report provides evidence that fluoxetine is a treatment option for patients with AD and severe obsessive-compulsive symptoms and highlights the importance of the serotoninergic system.

Aged↗

PubMed2002

[Alcohol-induced cognitive disorder: alcohol dementia].

Cognitive impairment is frequently observed in patients with alcohol misuse or alcohol addiction. Multiple cognitive functions are reduced in these patients. Frontal lobe functions, as planning, abstract thinking, set shifting or continuous performance are most frequently affected. Alcohol amnestic syndrome, alcohol dementia and the Wernicke-Korsakow-Syndrome constitute distinct entities. Alcohol dementia follows the diagnostic criteria of dementia with clear evidence for alcohol abuse or alcohol addiction. The diagnostic procedure of alcohol-induced cognitive impairment includes medical history, physical and neuropsychiatric examinations; laboratory examinations, neuropsychological assessment, brain imaging and electroencephalographic recordings. At the moment, there are no established treatment options for alcohol-induced cognitive impairment. Some evidence is provided that nootropics might be of benefit. Alcohol abstinence is a most important step. Psychosocial interventions are essential to support the patients in their daily activities.

Aged↗

PubMed2002

[Psychosocial therapy of patients with dementia].

The progressive cognitive and behavourial disturbancies in dementia diseases cause great emotional burden to patients, their families and caregivers. To relief this burden and to facilitate adequate coping strategies, psychosocial therapies intend to improve cognitive functions, self care abilities and emotional wellbeing of dementia patients. The therapeutic interventions address the patients, their caregivers and the adaption of the environment. Psychosocial therapies can be divided into cognitive training methods, behaviour orientated concepts, emotional orientated approaches and family interventions (1, 2, 12, 19). Most of these psychosocial therapies are only poor validated in randomized controlled trials. Nevertheless, they hold great promise to improve the quality of life and wellbeing of dementia patients and their caregivers. Thus they should be considered to be an integral part of a comprehensive therapeutic approach to dementia patients and their families.

Activities of Daily Living↗

PubMed2002

Pharmacological treatment strategies of residential primary care providers in dementia diseases--results of a representative survey in western Austria.

OBJECTIVE: The goal of this study was to investigate pharmacological treatment strategies used by residential primary care providers for patients with dementia. METHODS: A postal questionnaire survey was sent to all residential primary care providers, internists, neurologists and psychiatrists (n = 689) in the western region of Austria. RESULTS: The response rate (53 %) was similar in all four physician groups. Acetylcholinesterase inhibitors are considered to have a higher efficacy (p < 0.0005) compared to nootropic drugs. However, the vast majority of primary care providers (95 %) prescribe nootropic drugs. Two thirds (64 %) of the primary care providers prescribe acetylcholinesterase inhibitors. The dementia subtype influences the prescription frequency of acetylcholinesterase inhibitors, but not the specific choice of nootropic compound. Half of the primary care providers (52 %) combine antidementia drugs. Nearly two-thirds (62 %) of all primary care providers frequently prescribe antidepressants. Specific serotonin reuptake inhibitors are applied by the majority of primary care providers (96 %). About one-third (39 %) of primary care providers and internists (29 %) prescribe tricyclic antidepressants. Antipsychotics are applied frequently by around a quarter (29 %) of all physicians. More than half of primary care providers (62 %) and internists (58 %) treat patients with typical antipsychotics. Psychiatrists and neurologists are significantly more reluctant to prescribe tricyclic antidepressants and typical antipsychotics. CONCLUSIONS: Despite the lack of scientific evidence, residential primary care providers combine antidementia drugs very frequently. Therefore, controlled studies on combination therapies are urgently needed; in contrast to neurologists and psychiatrists, primary care providers and internists frequently prescribe tricyclic antidepressants and typical antipsychotics. The reasons for this should be clarified in further studies.

Antidepressive Agents↗

PubMed2001

Magnetic stimulation induces neuronal c-fos via tetrodotoxin-sensitive sodium channels in organotypic cortex brain slices of the rat.

Repetitive transcranial magnetic stimulation is a novel non-invasive method with antidepressant properties, where electromagnetic fields are applied via an electrode. The aim of the present study was to investigate in an in vitro model if magnetic stimulation may activate the transcription factor c-fos. Organotypic brain slices of the parietal cortex were cultured for 2 weeks and then treated with a magnetic stimulator. Immunohistochemistry was used to detect c-fos like immunoreactivity. We show that magnetic stimulation (1 Hz, 10 min, 75% machine output/magstim 200 rapid stimulator) transiently enhanced c-fos 3-6 h after stimulation. Co-localization experiments revealed that c-fos was expressed in neurons but not astroglia. The activation of c-fos by magnetic stimulation was inhibited by the sodium-channel blocker tetrodotoxin (TTX) (10 microM). It is concluded that magnetic stimulation induces neuronal c-fos via TTX-sensitive sodium channels in organotypic cortex slices.

Animals↗

PubMed2001

Striatal dopamine transporter function in dementia with Lewy bodies and Parkinson's disease.

The aim of this study was to compare parkinsonian features and loss of striatal dopamine transporter (DAT) function in patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PD), matched for age and disease duration. Twenty patients with DLB. 24 PD patients and 10 matched controls were examined with SPET using a dual-head camera and the dopamine-transporter ligand 123I-beta-CIT (148 MBq). Moreover, in a subgroup of patients (16 DLB and 20 PD patients), subscores of the Unified Parkinson's Disease Rating Scale (UPDRS)-motor examination (ME) subscale were obtained during "practical off", i.e. 12 h following withdrawal of antiparkinsonian therapy. Compared with controls, striatal/cerebellar (S/C) ratios of DAT binding were significantly reduced in both DLB and PD, deficits being more marked in DLB patients (controls 7.2 +/- 1.2, DLB 3.3 +/- 1, PD 4.2 +/- 1.4; means +/- SD). The side-to-side differences in the S/C ratios were lower in the DLB group and the controls than in PD patients (0.4 +/- 0.4. 0.2 +/- 0.2 and 0.6 +/- 0.3, respectively, P<0.05). The total UPDRS-ME scores during practical-off were significantly higher in the DLB than in the PD group (41.2 +/- 12.7 vs 26.6 +/- 15.3, P<0.01). The side-to-side differences of the summed UPDRS extremity subscores were smaller in the DLB than in the PD group (2.2 +/- 2.3 vs 7.4 +/- 3.9, P<0.0001). Our findings suggest that parkinsonism evolves largely symmetrically and progresses more rapidly with more severe loss of striatal dopamine transporter function in DLB compared to PD. Whether these findings are helpful in the differential diagnosis of DLB and PD needs to be examined in further studies.

Aged↗

PubMed2001

Nerve growth factor and glial cell line-derived neurotrophic factor restore the cholinergic neuronal phenotype in organotypic brain slices of the basal nucleus of Meynert.

Loss of cholinergic neurons is found in the medial septum and nucleus basalis of Meynert in Alzheimer's disease. Recent observations suggest that cholinergic neurons down-regulate their phenotype and that growth factors may rescue cholinergic neurons. The aim of this study was to investigate whether cholinergic neurons of the basal nucleus of Meynert can be cultured in rat organotypic slices, and if nerve growth factor and glial cell line-derived neurotrophic factor can rescue the cholinergic phenotype. In the organotypic slices, glial cells, GABAergic and cholinergic neurons were visualized using immunohistochemistry. The number of cholinergic neurons was found to be very low in slices cultured without exogenous nerve growth factor. Analysis of nerve growth factor tissue levels by enzyme-linked immunosorbent assay revealed very low endogenous tissue levels. When slices were incubated with 100ng/ml nerve growth factor during the initial phase of culturing, a stable expression of choline acetyltransferase was found for up to several weeks. After eight weeks in culture with nerve growth factor or two to three weeks after nerve growth factor withdrawal, numbers of detected cholinergic neurons decreased. Neurons incubated with nerve growth factor displayed a significantly enlarged cell soma compared to neurons without growth factors. In cultures incubated for up to nine weeks, it was also found that glial cell line-derived neurotrophic factor was capable of restoring the cholinergic phenotype. The low-affinity p75 and high-affinity trkA receptors, as well as the glial cell line-derived neurotrophic factor receptor GFRalpha-1, could be visualized in slices using immunohistochemistry. In conclusion, it is shown that, in the axotomized organotypic slice model, the number of cholinergic neurons is decreased, but can be partly restored by nerve growth factor and glial cell line-derived neurotrophic factor.

Acetylcholine↗

PubMed2001

Differential regulation of chromogranin A, chromogranin B and secretogranin II in rat brain by phencyclidine treatment.

Chromogranin A, chromogranin B and secretogranin II belong to the chromogranin family which consists of large protein molecules that are found in large dense core vesicles. Chromogranins are endoproteolytically processed to smaller peptides. This study was designed to elucidate the regulation of chromgranin expression by acute and subchronic phencyclidine administration. The behavioral syndrome produced by phencyclidine represents a pharmacological model for some aspects of schizophrenia [Jentsch and Roth (1999) Neuropsychopharmacology 20, 201-225]. Tissue concentrations of chromogranins were measured with specific radioimmunoassays. Alterations in secretogranin II gene expression were investigated by in situ hybridization. A single dose of phencyclidine (10mg/kg) led to a transient decrease in secretoneurin tissue levels in the prefrontal cortex after 4h followed by an increase in secretoneurin tissue levels after 12h. Repeated phencyclidine treatment (10mg/kg/day) for five days resulted in elevated secretoneurin levels in cortical areas whereas chromogranin A and chromogranin B tissue levels were unchanged. After the same treatment, a significant increase in the number of secretoneurin containing neurons was found in cortical layers II-III, and V-VI as revealed by immunocytochemistry. The increases in secretoneurin levels were paralleled by an increased number of secretogranin II messenger RNA containing neurons as well as by an increased expression of secretogranin II by individual neurons. The present study shows that secretoneurin II tissue concentration and secretogranin II messenger RNA expression is distinctly altered after acute and subchronic phencyclidine application. From these results we suggest that phencyclidine may induce synaptic alterations in specific brain areas and may contribute to a better understanding of synaptic dysfunction which may also occur in schizophrenia.

Animals↗

PubMed2000

Chronic repetitive transcranial magnetic stimulation enhances c-fos in the parietal cortex and hippocampus.

Repetitive transcranial magnetic stimulation (rTMS) is a novel non-invasive method with anti-depressant properties. However, the mechanism of activation on the cellular level is unknown. Twelve hours after the last chronic rTMS treatment (14 days, once per day, 20 Hz, 10 s, 75% machine output, the transcription factor c-fos was markedly increased in neurons in layers I-IV and VI of the parietal cortex and in few scattered neurons in the hippocampus of Sprague-Dawley rats. The cortical activation was not blocked by the NMDA antagonist MK-801. The increase of c-fos was not paralleled by an increased glial response and activation of cortical growth factors. Thus, it is concluded that chronic rTMS differentially activates parietal cortical layers and this might be involved in mediating anti-depressant activity in other brain areas.

Animals↗

PubMed2000

Co-distribution patterns of chromogranin B-like immunoreactivity with chromogranin A and secretoneurin within the human brainstem.

As members of the chromogranin family, chromogranin A, chromogranin B, and secretogranin II are acidic proteins found in large, dense core vesicles. They are endoproteolytically processed to smaller peptides and released after neuronal stimulation. Using immunocytochemistry, this study closely examines chromogranin B-like immunoreactivity within the human brainstem and then takes a comparative view of co-distribution patterns by chromogranin B, chromogranin A, and secretogranin II. We used an antiserum raised against a synthetic peptide (PE-11) present in the chromogranin B molecule. Secretogranin II was localized with an antiserum against secretoneurin, a 33 amino acid peptide, found within the secretogranin II precursor. Like chromogranin A and secretoneurin, chromogranin B is expressed through all levels of the human brainstem. Chromogranin B was exclusively detected in neuronal structures. The medial part of the substantia nigra pars reticulata, the nucleus interpeduncularis, the area of the central gray, and the raphe complex displayed a high density of PE-11-like immunoreactivity. Furthermore, a prominent staining was found in the medial, dorsal and gelatinous subnuclei of the solitary tract and the dorsal motor nucleus of vagus. The substantia gelatinosa of the caudal trigeminal nucleus and spinal cord were also very strongly PE-11-immunopositive. In conclusion, chromogranin B and secretogranin II showed similar distributions while neuronal localization typically differed from chromogranin A aside from a few exceptions. These findings may provide a framework for future research in revealing a functional role of chromogranin peptides in the human brainstem.

Adult↗

PubMed2000

Distribution of chromogranin B-like immunoreactivity in the human hippocampus and its changes in Alzheimer's disease.

Synapse loss is crucially involved in cognitive decline in Alzheimer's disease (AD). This study was performed to investigate the distribution and density of chromogranin B-like immunoreactivity in the hippocampus of control compared to AD brain. Chromogranin B is a large precursor molecule found in large dense-core vesicles. For immunocytochemistry we used an antiserum raised against a synthetic peptide (PE- 11) present in the chromogranin B molecule. Chromogranin B-like immunoreactivity was concentrated in the terminal field of mossy fibers, the inner molecular layer of the dentate gyrus and in layer II of the entorhinal cortex. In AD, chromogranin B was detected in neuritic plaques. The density of chromogranin B-like immunoreactivity was significantly reduced in the inner molecular layer of the dentate gyrus and in layers II, III and V of the entorhinal cortex in AD brains. The present study demonstrates that chromogranin B is a marker for human hippocampal pathways. It is particularly suitable for studying nerve fibers terminating at the inner molecular layer of the dentate gyrus. It is present in neuritic plaques, and its density is reduced in a layer-specific manner.

Aged↗

PubMed2000

Further evidence that behavioral tests and neuropeptide mRNA and tissue level alterations can differentiate between typical and atypical antipsychotic drugs.

This study was designed to compare some behavioral and biochemical effects of chronic treatment with a range of antipsychotic drugs. Gene expression of enkephalin, chromogranin A, chromogranin B, and secretogranin II and their respective peptide products were studied with in situ hybridization and radioimmunoassays after daily oral administration of haloperidol, clozapine, risperidone, or zotepine for 21 days. In behavioral tests, significant catalepsy was induced by haloperidol only. All four antipsychotic drugs increased hind paw retraction time but only haloperidol also increased forelimb retraction time. In the caudate putamen, haloperidol increased both enkephalin mRNA expression and enkephalin tissue levels. Neither of these parameters was altered by the other three drugs. In the prefrontal cortex, antipsychotic drugs generated a distinct pattern of gene expression in two regards. First, the dopamine D(2) receptor antagonist, haloperidol, did not significantly alter synaptic protein levels or their encoding mRNAs. Secondly, there was a differential change in tissue levels and mRNA expression since secretogranin II was not affected by any tested antipsychotic drug. This study shows that different types of antipsychotic drug induce distinct behavioural effects as well as differential changes in the biosynthesis of synaptic proteins and their encoding mRNAs. The data reinforce the notion that haloperidol can be classed as a typical antipsychotic drug whilst clozapine, zotepine, and risperidone reflect their atypical classification.

Animals↗