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1.
J Neural Transm (Vienna) ; 118(5): 773-81, 2011 May.
Article in English | MEDLINE | ID: mdl-21461962

ABSTRACT

Former studies on the effects of physical exercise, physical and occupational therapy (PT, OT) and speech and swallowing therapy (ST, SwT) in Parkinson's disease (PD) have demonstrated little or uncertain effects. New pathophysiological concepts have been developed. Recent controlled high-level studies demonstrate improvement of mobility and balance after training of muscular strength and endurance, trunk control, and amplitude and rhythmicity of movements (treadmill). Attentional and cognitive strategies were found to enforce body awareness and improve movement sequences. Dance, sensory (auditory, visual, tactile) and cognitive cueing are effective for problems of gait and balance. Whether PT and OT reduce the risk of falls remains uncertain. ST including Lee Silverman Voice Treatment has been shown to relieve speech problems. SwT and OT are frequently applied, however, further studies are necessary. Therapeutic interventions need to be evaluated with regard to consistency, intensity, frequency, duration, side effects, home versus institution based and standardized versus individualized training, quality standards, practicability in real life, and cost-effectiveness. Parkinson patients should resume or continue physical exercise as long as possible. There is hope that regular sport may modify PD risk and progression.


Subject(s)
Deglutition/physiology , Exercise Therapy/methods , Occupational Therapy/methods , Parkinson Disease/rehabilitation , Speech Therapy/methods , Humans
2.
Neuropsychiatr ; 24(2): 67-87, 2010.
Article in German | MEDLINE | ID: mdl-20605003

ABSTRACT

The Austrian Alzheimer Society developed evidence-based guidelines based on a systematic literature search and criteria-guided assessment with subsequent transparent determination of grades of clinical recommendation. The authors evaluated currently available therapeutic approaches for the most common forms of dementia and focused on diagnosis and pharmacological intervention, taking into consideration the situation in Austria. The purpose of these guidelines is the rational and cost-effective use of diagnostic and therapeutic measures in dementing illnesses. Users are physicians and all other providers of care for patients with dementia in Austria.


Subject(s)
Dementia/diagnosis , Dementia/drug therapy , Evidence-Based Medicine , Nootropic Agents/therapeutic use , Aged , Aged, 80 and over , Amino Acids/adverse effects , Amino Acids/therapeutic use , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Cholinesterase Inhibitors/adverse effects , Cholinesterase Inhibitors/therapeutic use , Cognition Disorders/diagnosis , Cognition Disorders/drug therapy , Cross-Sectional Studies , Dementia/epidemiology , Dementia/etiology , Drug Therapy, Combination , Female , Ginkgo biloba , Humans , Incidence , Life Style , Long-Term Care , Male , Medication Adherence , Memantine/adverse effects , Memantine/therapeutic use , Middle Aged , Plant Extracts/adverse effects , Plant Extracts/therapeutic use , Population Dynamics , Psychotropic Drugs/adverse effects , Psychotropic Drugs/therapeutic use , Randomized Controlled Trials as Topic
3.
Ther Umsch ; 64(1): 5-8, 2007 Jan.
Article in German | MEDLINE | ID: mdl-17221818

ABSTRACT

The clinical criteria of Parkinson's disease are akinesia in combination with at least one of the following three symptoms: tremor (asymmetrical resting tremor), rigidity, impairment of posture, gait and balance. Symptomatic and atypical parkinsonian syndromes are ruled out by history, clinical examination, cranial CT, MRI, SPECT or PET. Patients with Parkinson's disease respond to levodopa or dopaminagonists throughout the course of the disease. Parkinson's disease is also characterised by various vegetative symptoms, impairment of olfaction, anxiety, depression, and with increasing age also by cognitive deficits and dementia.


Subject(s)
Parkinson Disease , Age Factors , Aged , Antiparkinson Agents/administration & dosage , Antiparkinson Agents/therapeutic use , Cognition Disorders/etiology , Dementia/etiology , Diagnosis, Differential , Dopamine Agonists/administration & dosage , Dopamine Agonists/therapeutic use , Humans , Levodopa/administration & dosage , Levodopa/therapeutic use , Middle Aged , Parkinson Disease/complications , Parkinson Disease/diagnosis , Parkinson Disease/diagnostic imaging , Parkinson Disease/drug therapy , Parkinson Disease/genetics , Positron-Emission Tomography , Risk Factors , Time Factors , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed
4.
J Neurosci ; 21(15): 5804-12, 2001 Aug 01.
Article in English | MEDLINE | ID: mdl-11466452

ABSTRACT

Marked expression of neuropeptide Y (NPY) and its Y2 receptors in hippocampal mossy fibers has been reported in animal models of epilepsy. Because NPY can suppress glutamate release by activating presynaptic Y2 receptors, these changes have been proposed as an endogenous protective mechanism. Therefore, we investigated whether similar changes in the NPY system may also take place in human epilepsy. We investigated Y1 and Y2 receptor binding and NPY immunoreactivity in hippocampal specimens that were obtained at surgery from patients with temporal lobe epilepsy and in autopsy controls. Significant increases in Y2 receptor binding (by 43-48%) were observed in the dentate hilus, sectors CA1 to CA3, and subiculum of specimens with, but not in those without, hippocampal sclerosis. On the other hand, Y1 receptor binding was significantly reduced (by 62%) in the dentate molecular layer of sclerotic specimens. In the same patients, the total lengths of NPY immunoreactive (NPY-IR) fibers was markedly increased (by 115-958%) in the dentate molecular layer and hilus, in the stratum lucidum of CA3, and throughout sectors CA1 to CA3 and the subiculum, as compared with autopsies. In nonsclerotic specimens, increases in lengths of NPY-IR fibers were more moderate and statistically not significant. NPY mRNA was increased threefold in hilar interneurons of sclerotic and nonsclerotic specimens. It is suggested that abundant sprouting of NPY fibers, concomitant upregulation of Y2 receptors, and downregulation of Y1 receptors in the hippocampus of patients with Ammon's horn sclerosis may be endogenous anticonvulsant mechanisms.


Subject(s)
Epilepsy, Temporal Lobe/metabolism , Hippocampus/metabolism , Neuronal Plasticity , Neurons/metabolism , Neuropeptide Y/metabolism , Receptors, Neuropeptide Y/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Autoradiography , Cell Count , Child , Child, Preschool , Drug Resistance , Epilepsy, Temporal Lobe/pathology , Epilepsy, Temporal Lobe/surgery , Female , Hippocampus/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Neurons/pathology , Neuropeptide Y/genetics , RNA, Messenger/metabolism , Radioligand Assay
5.
Acta Neurol Scand Suppl ; 95: 123-6, 1983.
Article in English | MEDLINE | ID: mdl-6428144

ABSTRACT

Long-term treatment of parkinsonian patients with levodopa (plus decarboxylase inhibitor) leads to decreasing levodopa efficacy and increasing side-effects. Then main therapeutic problems are on-off phenomena, end-of-dose akinesia and levodopa-induced dyskinesias. Deprenyl, a selective MAO-B inhibitor, has produced good therapeutic effects in combination either with levodopa alone or with levodopa plus decarboxylase inhibitor in the treatment of end-of-dose akinesia and on-off phenomena. In an open trial with 48 parkinsonian patients deprenyl was added to previous levodopa plus decarboxylase-inhibitor therapy. Good effects were achieved in respect of mild on-off phenomena and end-of-dose akinesia, minor success in the alleviation of dyskinesia and depression. In four further patients with a post-traumatic parkinsonian syndrome, no improvement of rigidospasticity and vigilance was demonstrable.


Subject(s)
Parkinson Disease/drug therapy , Phenethylamines/therapeutic use , Selegiline/therapeutic use , Aged , Benserazide/therapeutic use , Carbidopa/therapeutic use , Drug Evaluation , Drug Therapy, Combination , Female , Humans , Levodopa/therapeutic use , Male , Middle Aged , Parkinson Disease/physiopathology , Selegiline/adverse effects
6.
Eur J Hum Genet ; 7(3): 397-400, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10234518

ABSTRACT

Patients with idiopathic Parkinson's disease (IPD) are described as having markedly decreased novelty seeking characteristics. Since recent publications suggest an association between the dopamine D4 receptor polymorphism and novelty seeking, we investigated this polymorphism in a group of 122 patients with IPD and 127 healthy control subjects. We found similar allele and genotype frequencies in both groups and no association with the age of onset of symptoms. Therefore, the dopamine D4 receptor polymorphism does not confer genetic susceptibility to IPD and cannot explain the decreased novelty seeking in IPD patients.


Subject(s)
Parkinson Disease/genetics , Polymorphism, Genetic , Receptors, Dopamine D2/genetics , Aged , Female , Humans , Male , Receptors, Dopamine D4
7.
Neurobiol Aging ; 17(4): 541-7, 1996.
Article in English | MEDLINE | ID: mdl-8832628

ABSTRACT

We hypothesized that metabolic products of the Alzheimer beta amyloid precursor protein (APP) might be targets for cells of the immune system. To test this hypothesis, peripheral blood lymphocytes from young and old healthy blood donors and patients with Alzheimer's disease were analysed for their responsiveness upon stimulation with amyloid beta protein as well as with four other synthetic peptides corresponding to parts of the APP sequence. Stimulation of resting blood lymphocytes from young and old healthy blood donors resulted in IL-2 receptor expression and proliferation in both age groups. In contrast, lymphocytes from the majority of patients with Alzheimer's disease did not proliferate, when stimulated with APP peptides, while their proliferative response to anti-CD3 was unimpaired. This lack of proliferative responsiveness to APP peptides was not due to apoptosis, but could reflect T cell anergy, as it was accompanied by unimpaired IL-2 receptor expression. The results suggest that autoreactive lymphocytes with specificity for metabolic products of APP occur in healthy individuals. These cells may be of relevance for the elimination of potentially amyloidogenic substances. This mechanism could be impaired in patients with Alzheimer's disease.


Subject(s)
Aging/metabolism , Alzheimer Disease/metabolism , Amyloid beta-Protein Precursor/pharmacology , Cell Division/drug effects , Lymphocytes/drug effects , Adolescent , Adult , Age Factors , Aged , Cell Line/drug effects , Female , Humans , Male
8.
Neurology ; 50(5 Suppl 5): S46-53, 1998 May.
Article in English | MEDLINE | ID: mdl-9591522

ABSTRACT

BACKGROUND: More than 50% of patients with Parkinson's disease develop motor response fluctuations (the 'wearing off" phenomenon) after more than five years of levodopa therapy. Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. OBJECTIVES: The primary objective was to evaluate the efficacy of tolcapone in reducing "wearing off" in levodopa treated, fluctuating parkinsonian patients. Secondary objectives included assessment of reduction in levodopa requirements, improvement in patients' clinical status, duration of improvements, and tolerability of tolcapone. METHODS: In this multicentre, randomised, double blind, placebo controlled trial, 58 patients received placebo, 60 received 100 mg tolcapone three times daily (tid), and 59 received 200 mg tolcapone tid, in addition to levodopa/benserazide. RESULTS: After three months with 200 mg tolcapone tid, "off" time decreased by 26.2% of the baseline value, "on" time increased by 20.6% (p < 0.01 vs. placebo), and the mean total daily levodopa dose decreased by 122 mg from the baseline dose of 676 mg (p < 0.01). These responses were maintained up to nine months. With 100 mg tolcapone tid, "off" time decreased by 31.5% (p < 0.05), "on" time increased by 21.3% (p < 0.01), and the mean total daily levodopa dose decreased by 109 mg from the baseline dose of 668 mg (p < 0.05). With 200 mg tolcapone tid, unified Parkinson's disease rating scale motor and total scores were significantly reduced, and quality of life (sickness impact profile) scores were significantly improved. Both dosages were well tolerated. Dyskinesia was the most often reported levodopa induced adverse event. Diarrhoea was the most often reported non-dopaminergic adverse event and the most frequent reason for withdrawal from the study: four patients in the 100 mg tolcapone tid group and six in the 200 mg tid group withdrew because of diarrhoea. CONCLUSION: Tolcapone prolongs "on" time in fluctuating parkinsonian patients while allowing a reduction in daily levodopa dosage, thereby improving the efficacy of long term levodopa therapy.


Subject(s)
Antiparkinson Agents/pharmacology , Benserazide/pharmacokinetics , Benzophenones/pharmacology , Catechol O-Methyltransferase Inhibitors , Dopamine Agents/pharmacokinetics , Enzyme Inhibitors/pharmacology , Levodopa/pharmacokinetics , Parkinson Disease/drug therapy , Aged , Antiparkinson Agents/adverse effects , Antiparkinson Agents/pharmacokinetics , Benserazide/administration & dosage , Benzophenones/adverse effects , Diarrhea/chemically induced , Dopamine Agents/administration & dosage , Double-Blind Method , Drug Administration Schedule , Drug Therapy, Combination , Dyskinesia, Drug-Induced/etiology , Enzyme Inhibitors/adverse effects , Europe , Female , Humans , Levodopa/administration & dosage , Male , Middle Aged , Nitrophenols , Parkinson Disease/enzymology , Tolcapone , Treatment Outcome
9.
Neuroscience ; 47(4): 843-51, 1992.
Article in English | MEDLINE | ID: mdl-1374541

ABSTRACT

Consistent findings in the hippocampi of patients with Alzheimer's disease are the presence of neurofibrillary tangles in pyramidal neurons and the loss of choline acetyltransferase activity due to degeneration of hippocampal cholinergic terminals. The present study sought to clarify, in the brains of five patients with Alzheimer's disease and four controls, whether the loss of cholinergic terminals in the hippocampal stratum pyramidale in Alzheimer's disease is related to degenerative changes in hippocampal pyramidal cells. A polyclonal antibody to human choline acetyltransferase was employed to visualize immunohistochemically cholinergic terminals. Hippocampal neurons were stained with Cresyl Violet, neurofibrillary tangles with thioflavin S and a monoclonal antibody against phosphorylated neurofilament (RT97). Quantification of the stained structures was performed in CA4, CA1 and the subiculum, on five sections selected from the entire anteroposterior extent of each hippocampus. In the group of Alzheimer patients, the densities of cholinergic terminals were homogeneously diminished in the three hippocampal subregions in comparison with the controls (32-33%). In contrast, a significant loss of pyramidal neurons was found only in CA1, and the density of neurofibrillary tangles was markedly increased only in CA1 and the subiculum in Alzheimer's disease. These findings suggest that there is no relationship between the loss of cholinergic terminals and the degeneration of pyramidal cells in the hippocampus of patients with Alzheimer's disease.


Subject(s)
Alzheimer Disease/enzymology , Alzheimer Disease/pathology , Choline O-Acetyltransferase/metabolism , Hippocampus/enzymology , Hippocampus/pathology , Aged , Aged, 80 and over , Analysis of Variance , Female , Humans , Immunoenzyme Techniques , Immunohistochemistry , Male , Neurofibrillary Tangles/ultrastructure , Neurons/enzymology , Neurons/pathology , Pyramidal Tracts/enzymology , Pyramidal Tracts/pathology , Reference Values , Staining and Labeling
10.
Neuroscience ; 32(3): 701-14, 1989.
Article in English | MEDLINE | ID: mdl-2601840

ABSTRACT

A qualitative and quantitative immunohistochemical study of cholinergic systems in the human hippocampal formation was performed with an antibody against choline acetyltransferase. Four control subjects and six patients with Alzheimer's disease, matched for age and post-mortem delay, were examined. Immunoreactive nerve fibres and terminals were visualized, but no cholinergic cell bodies were seen. The distribution of the fibres and terminals suggests that a major afferent cholinergic pathway enters the hippocampus dorsally via the fimbria-fornix, a minor input entering from the temporal lobe along the alvear path. The cholinergic innervation suffers some degenerative change in normal aged subjects, but decreases considerably in density in patients with Alzheimer's disease. The extent of the decrease differs somewhat among the subregions of the hippocampus, but is homogeneously distributed within each subregion, and throughout the rostrocaudal extent of the structure. Compensatory sprouting in reaction to denervation was not detected.


Subject(s)
Alzheimer Disease/enzymology , Choline O-Acetyltransferase/metabolism , Hippocampus/enzymology , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Male
11.
Mol Cell Endocrinol ; 117(2): 149-56, 1996 Mar 25.
Article in English | MEDLINE | ID: mdl-8737374

ABSTRACT

Expansion of CAG trinucleotide repeats in androgen receptor gene is present in patients with a rare X-linked inherited form of motor neuron disorder termed Kennedy's disease or spinal and bulbar muscular atrophy (SBMA). This is a late onset progressive disease often associated with mild signs of androgen insensitivity. Defects in androgen receptor (AR) action have been linked to the expansion of the CAG trinucleotide repeats and postulated to be the cause of the disease. We have identified a trinucleotide repeat of 45 in the N-terminus of the AR in two brothers with SBMA and several members in their family (range in the general population is 11-35). Treatment of the patients with androgens failed to improve their clinical symptoms and provided no hint of an anomalous function of the AR. Consistently, functional analysis of the mutant receptor showed hormone binding, transactivation and transrepression potentials identical to that of the wild-type receptor. These results together argue against SBMA being a loss of function mutation of the AR.


Subject(s)
Muscular Atrophy, Spinal/genetics , Mutation , Receptors, Androgen/genetics , Trinucleotide Repeats , Androgens/metabolism , Animals , Base Sequence , Cell Line , Cells, Cultured , Chlorocebus aethiops , DNA Primers , Female , Gene Expression , Humans , Male , Molecular Sequence Data , Pedigree
12.
Neuroreport ; 5(10): 1237-40, 1994 Jun 02.
Article in English | MEDLINE | ID: mdl-7919173

ABSTRACT

The antispastic agent and N-methyl-D-aspartate (NMDA) receptor antagonist memantine has recently been proposed as a neuroprotective drug for use in patients with dementia syndromes with primarily temporal lobe pathology, e.g. senile dementia of Alzheimer type or dementia in Parkinson's disease. In a quantitative autoradiographic study in human post mortem hippocampus, memantine was able to inhibit binding of the noncompetitive NMDA-antagonist [3H]MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate) with inhibition constants between 3 and 10 microM, being about a factor of 10 more potent than the dissociative anaesthetic and NMDA receptor antagonist (+/-)ketamine. As these inhibition constants are well within the therapeutic concentration range of memantine, antagonism of endogenous glutamate at limbic NMDA receptors may be one molecular mechanism by which memantine is beneficial in dementia syndromes.


Subject(s)
Dizocilpine Maleate/pharmacokinetics , Hippocampus/metabolism , Memantine/pharmacology , Receptors, N-Methyl-D-Aspartate/metabolism , Aged , Autoradiography , Depression, Chemical , Female , Hippocampus/drug effects , Humans , In Vitro Techniques , Ketamine/pharmacology , Male , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/drug effects
13.
Ann Thorac Surg ; 48(1): 15-8, 1989 Jul.
Article in English | MEDLINE | ID: mdl-2764595

ABSTRACT

In a randomized study, 63 patients were investigated for the benefits of cryoanalgesia after thoracotomy. Analgesia and its dependent effects such as enhancement of mobility, respiratory function, and reduced need of narcotics were evaluated. No significant differences in these variables were observed between the cryoanalgesia group and the control group. However, moderate to severe neuralgia was found in a number of patients in the cryoanalgesia group in the late postoperative period. Cryoanalgesia for pain relief after thoracotomy is not recommended.


Subject(s)
Analgesia/methods , Hypothermia, Induced , Neuralgia/etiology , Pain, Postoperative/prevention & control , Thoracotomy , Adult , Aged , Double-Blind Method , Female , Humans , Hypothermia, Induced/adverse effects , Intraoperative Care , Male , Middle Aged , Random Allocation
14.
Int J Dev Neurosci ; 16(5): 391-401, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9829175

ABSTRACT

Trophic factors play important roles in survival and nerve fiber growth of cholinergic interneurons in the striatum in vivo and in vitro. In this study an organotypic slice model was used to investigate the effects of nerve growth factor and the novel factors glial cell line-derived neurotrophic factor and neurturin as well as other trophic factors on the striatal acetylcholine tissue levels: During culturing over 2 weeks acetylcholine tissue levels markedly decreased, representing degeneration of cholinergic neurons. When striatal slices were cultured for 2 weeks in the presence of 100 ng/ml nerve growth factor tissue levels of acetylcholine and the expression of choline acetyltransferase-like immunoreactivity and mRNA, as well as the muscarinic M2 autoreceptor mRNA were markedly enhanced compared to slices cultured without or with 10 ng/ml nerve growth factor. A single administration of nerve growth factor had no effect on acetylcholine tissue levels suggesting that nerve growth factor does not directly increase acetylcholine synthesis. All other trophic factors (glial cell line-derived neurotrophic factor, neurturin, brain-derived neurotrophic factor, neurotrophin-3 and -4/5, fibroblast growth factor-2, insulin like growth factor-I) had no effects on acetylcholine tissue levels. Thus, the organotypic slice model is a suitable system to study the effects of trophic factors and it is concluded that nerve growth factor selectively enhances acetylcholine tissue levels, indicating protection of cholinergic interneurons in the dorsal striatum.


Subject(s)
Acetylcholine/metabolism , Corpus Striatum/drug effects , Nerve Growth Factors/pharmacology , Nerve Tissue Proteins/pharmacology , Animals , Axotomy , Choline/pharmacology , Corpus Striatum/cytology , Corpus Striatum/metabolism , Glial Cell Line-Derived Neurotrophic Factor , Interneurons/drug effects , Interneurons/metabolism , Neurturin , Organ Culture Techniques , Rats
15.
J Neurol ; 235(2): 99-101, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3430199

ABSTRACT

Forty patients with Parkinson's disease were compared with 33 normal controls with respect to their performance in the Wechsler Adult Intelligence Scale subtests "information", "similarities", "block design", and "picture completion", in a test for visual neglect (Hamsher's line cancellation test) and in tests for visuospatial and visuorotational abilities (cube task from Amthauer's intelligence structure test and Rybakoff figure test, as revised by Meili). The findings show that the patients scored significantly worse than the controls (Mann-Whitney U test, P = 0.004) in the Rybakoff figure test, testing visual concept finding, imagination and visual rotation. In the other tests no significant differences were found between the patients and the controls. The deficit of the patients in the figure test of Rybakoff correlated significantly with tremor (P = 0.013), akinesia (P = 0.009), disability (P = 0.043), and age (P = 0.004, Spearman rank correlation).


Subject(s)
Parkinson Disease/physiopathology , Psychomotor Performance/physiology , Space Perception/physiology , Visual Perception/physiology , Aged , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Visual Pathways/physiopathology
16.
Neurosci Lett ; 150(2): 191-4, 1993 Feb 19.
Article in English | MEDLINE | ID: mdl-8469419

ABSTRACT

Adenosine A1 receptors were visualized in human hippocampus using [3H]8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as a radioactive ligand probe. The receptor antagonists caffeine, the xanthine derivative KFM 19 and the carbamazepine analogue oxcarbazepine displaced [3H]DPCPX binding homogeneously without any marked difference between the individual layers in the investigated hippocampal subregions (n = 4). Ki's in the individual layers were in a range between 8.5 +/- 6.5 microM and 18.9 +/- 16.0 microM for caffeine and 11.5 +/- 2.8 nM and 18.1 +/- 14.1 nM for KFM 19. Ki's could not be calculated for oxcarbazepine as the IC50's were greater than 100 microM with estimated IC25's varying between 51.2 +/- 53.3 microM and 179.9 +/- 89.9 microM. Antagonism of endogenous adenosine at A1 receptors may thus explain part of the clinical effects of caffeine in humans and possibly exclusively the behavioral effects of KFM 19 in non-human primates.


Subject(s)
Hippocampus/metabolism , Purinergic Antagonists , Xanthines/metabolism , Xanthines/pharmacology , Aged , Anticonvulsants/pharmacology , Autoradiography , Binding, Competitive , Caffeine/pharmacology , Carbamazepine/analogs & derivatives , Carbamazepine/pharmacology , Female , Hippocampus/drug effects , Humans , Male , Middle Aged , Oxcarbazepine , Receptors, Purinergic/drug effects , Receptors, Purinergic/metabolism
17.
Neurosci Lett ; 169(1-2): 219-22, 1994 Mar 14.
Article in English | MEDLINE | ID: mdl-7914016

ABSTRACT

Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) have been investigated with regard to their potency to inhibit [3H] alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid (AMPA) binding in human hippocampus in a quantitative autoradiographic study. With dissociation constants (KD) of [3H]AMPA binding and inhibition concentrations (IC50) of L-BOAA, 6-OH-DOPA and L-glutamate obtained from saturation and displacement experiments inhibition constants (Ki) for the inhibition of [3H]AMPA binding in individual hippocampal subregions could be calculated. They were between 5.2 +/- 2.9 and 35.1 +/- 39.9 microM for L-BOAA and 39.1 +/- 26.8 and 59.4 +/- 44.1 microM for 6-OH-DOPA. L-BOAA was equally potent as the endogenous agonist L-glutamate with Ki's between 13.1 +/- 3.9 and 21.4 +/- 12.1 microM (n = 4, mean +/- S.D.). Limbic system symptoms like cognitive deficits, mood disturbances and vivid dreams observed in patients with the motor neuron disease neurolathyrism may thus well be mediated by agonistic action of L-BOAA at AMPA glutamate receptors in hippocampus.


Subject(s)
Amino Acids, Diamino , Dihydroxyphenylalanine/analogs & derivatives , Hippocampus/metabolism , Receptors, AMPA/antagonists & inhibitors , beta-Alanine/analogs & derivatives , Aged , Aged, 80 and over , Autoradiography , Binding, Competitive/drug effects , Dihydroxyphenylalanine/pharmacology , Glutamates/pharmacology , Glutamic Acid , Hippocampus/drug effects , Humans , In Vitro Techniques , Pyramidal Cells/drug effects , Pyramidal Cells/metabolism , beta-Alanine/pharmacology
18.
Neurosci Lett ; 177(1-2): 11-4, 1994 Aug 15.
Article in English | MEDLINE | ID: mdl-7824159

ABSTRACT

The lateral vestibular nucleus (LVN, nucleus of Deiters) was examined in the brains of four control subjects and four patients with dementia of the Alzheimer type (DAT). Neuronal counts on sections stained with silver and a polyclonal antibody to human choline acetyltransferase (ChAT) revealed an undiminished number of LVN neurons in patients with DAT. Numerous silver-stained neurofibrillary tangles (NFTs) were found in the DAT group, some also in the LVN of controls. These findings suggest that DAT affects LVN neurons, however without causing neuronal loss.


Subject(s)
Alzheimer Disease/pathology , Neurofibrillary Tangles/pathology , Neurons/pathology , Vestibular Nuclei/pathology , Aged , Aged, 80 and over , Brain Stem/enzymology , Brain Stem/pathology , Cell Count , Choline O-Acetyltransferase/analysis , Female , Humans , Male , Nerve Tissue Proteins/analysis , Neurons/enzymology , Silver Staining , Vestibular Nuclei/enzymology
19.
Neurosci Lett ; 110(1-2): 210-5, 1990 Mar 02.
Article in English | MEDLINE | ID: mdl-1970142

ABSTRACT

The numbers of silver-stained senile plaques and plaques containing tyrosine hydroxylase (TH)-like immunoreactivity were counted in the neocortex, amygdala and hippocampus of control subjects and patients with Alzheimer's disease, and compared with the density of TH-positive nerve fibers. The number of silver-stained senile plaques was lowest in the hippocampus and highest in the amygdala, and increased in all three structures in relation to the degree of dementia in the patients. A small proportion of plaques in the hippocampus of the most demented subjects and a large proportion of plaques in the amygdala were TH-positive. No TH-like immunoreactivity was found in plaques in the neocortex, although this structure contained almost as many silver-stained senile plaques and was as densely innervated by TH-positive fibers as the amygdala. The number of plaques containing TH-like immunoreactivity was, therefore, not proportional to the innervation of the structures by TH-positive fibers, nor to the total number of plaques in the structure, suggesting that the dissociation between the proportion of TH-positive plaques in the amygdala and neocortex may be due to differences in the populations of TH-positive fibers innervating the structures.


Subject(s)
Alzheimer Disease/enzymology , Tyrosine 3-Monooxygenase/metabolism , Aged , Aged, 80 and over , Alzheimer Disease/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged
20.
Neurosci Lett ; 187(2): 107-10, 1995 Mar 03.
Article in English | MEDLINE | ID: mdl-7783956

ABSTRACT

The excitotoxic amino acid domoate causes anterograde amnesia and memory deficits while the excitotoxin L-beta-oxalyl-amino-alanine (L-BOAA) is considered the causative agent of the motoneurone disorder, neurolathyrism. Employing quantitative autoradiography we investigated the potency of domoate and L-BOAA to inhibit [3H]kainate binding in human hippocampus. Domoate inhibited binding of [3H]kainate with inhibition constants between 5.8 +/- 2.8 nM (deep layers of gyrus parahippocampalis) and 200.9 +/- 247.8 nM (CA1 region of hippocampus). It was about a thousandfold more potent than L-BOAA with inhibition constants between 2.1 +/- 0.5 microM (superficial layers of gyrus parahippocampalis) and 51.0 +/- 41.9 microM (CA2/3 region of hippocampus). Interestingly, L-BOAA showed lowest affinity to [3H]kainate binding sites in those regions in which domoate showed highest affinity (e.g. CA2/3) and vice versa (e.g. CA1). These data further support the notion that the neurological symptoms observed after domoate intoxication are due to an excitotoxic action at kainate receptors and provide evidence for heterogeneity of kainate receptors in human hippocampus.


Subject(s)
Amino Acids, Diamino , Hippocampus/metabolism , Kainic Acid/analogs & derivatives , Kainic Acid/metabolism , beta-Alanine/analogs & derivatives , Aged , Autoradiography , Binding Sites/drug effects , Cadaver , Humans , Kainic Acid/antagonists & inhibitors , Kainic Acid/pharmacology , Neurotoxins/pharmacology , beta-Alanine/pharmacology
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