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S Hoyer

Publications and source records attributed to S Hoyer.

At least 19 recordsLinked to original sources
PubMed2006

From benefit to damage. Glutamate and advanced glycation end products in Alzheimer brain.

The glutamatergic system is the most widespread neurotransmitter system in the mammalian brain. It is connected to the acetylcholinergic neurotransmitter system to form the glutamatergic/aspartatergic-acetylcholinergic circuit, which is the morphobiochemical basis of learning, memory and cognition assisted by the glutamatergic N-methyl-D-aspartate receptor, which mediates long-term potentiation as the fundamental molecular mechanisms of these mental capacities. Glutamate and acetylcholine as ligands of the two neurotransmitter systems are products of the neuronal glucose metabolism as holds true also for advanced glycation end products (AGEs), which are markers of damaged and/or aged proteins. During normal aging, both the neurotransmitters glutamate and acetylcholine undergo strong functional variations. Their synthesis was found to be reduced as a common feature. In contrast, basal release of acetylcholine and receptor number decrease, whereas basal release of glutamate and receptor number increase. AGEs increase during aging obviously preferentially in glutamatergic pyramidal neurons in cerebral cortical layers prone to neurodegeneration. In sporadic Alzheimer disease (SAD), glutamate concentration was shown to fall since it may serve as a substitute for lacking glucose in the beginning of the disease. In contrast, glutamate receptor density was found to be much less involved indicating an excessive activation of the glutamatergic neurotransmitter system particularly via the NMDA receptor, mediating endogenous excitotoxicity. The morphological hallmarks of SAD neuritic plaques and neurofibrillary tangles have been demonstrated to crosslink with AGEs causing an increased rate of free radical production. First data from animal studies and investigations on human beings may indicate that the NMDA receptor antagonist memantine may have beneficial effects on the course of SAD and its clinical symptoms.

Acetylcholine↗
PubMed2006

Alois Alzheimer revisited: differences in origin of the disease carrying his name.

Based on the means of his time, Alois Alzheimer supposed that the disease, later carrying his name, is a disease of older age, and that the pathomorphological structures he described are due to disturbances in brain metabolism. In this contribution, it is discussed which cellular metabolic abnormalities may be representative for age-related sporadic Alzheimer disease (SAD) the predominant form of SAD in contrast to the very rare hereditary early-onset form. In focus are disturbances in glucose/energy metabolism which involve the deficits in acetylcholine, cholesterol and UDP-N-acetylglucosamine beside ATP. Another leading abnormality is the defect in cell membrane composition. The interrelation between abnormal glucose/energy metabolism and membrane defect may be assumed to form the basis for the induction of both the perturbed metabolism of the amyloid precursor protein leading to increased formation of beta-amyloid and hyperphosphorylation of tau-protein destroying cell structures. Alois Alzheimer may have been so prescient to assume most of this 100 years ago.

Age of Onset↗
PubMed2006

Differentiated effect of ageing on the enzymes of Krebs' cycle, electron transfer complexes and glutamate metabolism of non-synaptic and intra-synaptic mitochondria from cerebral cortex.

The effect of ageing on the activity of enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism was studied in three different types of mitochondria of cerebral cortex of 1-year old and 2-year old male Wistar rats. We assessed the maximum rate (V(max)) of the mitochondrial enzyme activities in non-synaptic perikaryal mitochondria, and in two populations of intra-synaptic mitochondria. The results indicated that: (i) in normal, steady-state cerebral cortex the values of the catalytic activities of the enzymes markedly differed in the various populations of mitochondria; (ii) in intra-synaptic mitochondria, ageing affected the catalytic properties of the enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism; (iii) these changes were more evident in intra-synaptic "heavy" than "light" mitochondria. These results indicate a different age-related vulnerability of subpopulations of mitochondria in vivo located into synapses than non-synaptic ones.

Aging↗
PubMed2006

Odour and taste sensitivity is associated with body weight and extent of misreporting of body weight.

BACKGROUND: Sensory factors are important determinants of appetite and food choices but little is known about the relationship between body weight and sensory capabilities. OBJECTIVE: To investigate the relationship between measured body weights, misreporting of body weight and sensory capabilities. DESIGN: In a cross-sectional sensory study, body weight was assessed by measured and self-reported body weight in healthy men (n=130) and women (n=181). Sensory capabilities were assessed as odour detection and identification, and detection for salty, sweet, sour and bitter taste. RESULTS: Odour detection, odour identification and taste perception scores were lower in subjects with a BMI >or=28 kg/m(2) than in subjects with a BMI <28 kg/m(2) in the age group <65 years whereas in subjects >or=65 years scores were higher in subjects with a BMI >or=28 kg/m(2) than in subjects with a BMI <28 kg/m(2) (BMI*age group: P=0.015, 0.053 and 0.015, respectively). Independent of age, scores were highest in under reporters of body weight (P=0.008, 0.001 and 0.017). Differences in taste perception could be attributed to sour (P=0.015) and bitter (P=0.026) perception, but not to salty or sweet perception. CONCLUSION: Relationship between sensory capabilities and body mass is age dependent. Compared to overweight subjects, the sensory capabilities of normal weight individuals appear to be higher (<65 years) and lower (>or=65 years). At any age, however, subjects who under reported their body weight show higher sensory capabilities.

Adult↗
PubMed2005

Central administration of alloxan impairs glucose tolerance in rats.

By means of oral glucose tolerance test (OGTT), we investigated glucose tolerance in rats pre-treated with intracerebroventricular and subcutaneous non-diabetogenic dose of betacytotoxic drug alloxan 7 days before OGTT. Being normoglycemic and normoinsulinemic pre-OGTT, at 30 minutes post-OGTT, alloxan intracerebroventricularly-treated rats had a lower glucose and a higher insulin plasma levels in comparison with controls or alloxan subcutaneously treated animals. Centrally administered alloxan seems to have brain related effect on the regulation of peripheral glucose tolerance and insulin secretion.

Alloxan↗
PubMed2004

Relationship between cerebral energy metabolism in parietotemporal cortex and hippocampus and mental activity during aging in rats.

The present investigation demonstrates differences in both formation and utilization of the energy-rich compounds adenosine triphosphate ATP and creatine phosphate (CrP) in behaviorally well and poorly performing inbred male Wistar rats in parietotemporal cerebral cortex and hippocampus with aging from 1 to 2ys. Also, differences in learning and memory capacities (behavior) became obvious. By holeboard testing, good (GP) and poor performers (PP) have been discriminated. The pools of energy-rich phosphates as determined in parietotemporal cerebral cortex and in hippocampus under resting conditions were found to be reduced by nearly 10% for both creatine phosphate and the whole available energy pools in PP as compared to GP. Aging from 1 to 2y diminished the concentrations of energy-rich phosphates in the cerebral areas studied and in both GP and PP under resting conditions. Additionally, an age-related aggravation of the energy deficit became obvious between GP and PP. Repeated mental activation from 1y to 2y resulted in the maintenance of improvement as registered for the mean run time and the number of visited/revisited holes in GP. In contrast, PP deteriorated (mean run time), and could not maintain improvement (number of visited/revisited holes) over time. Repeated mental activation normalized the energy pool by increased formation of the energy-rich compounds ATP and CrP in both cerebral areas studied in GP and PP. However, differences became obvious between GP and PP. The energy-turnover in the latter group was found to be significantly reduced for both cerebral areas studied. GP could meet the enhanced energy demand of mental activation during aging by increasing formation and utilization of energy. PP could increase energy formation but were unable to sufficiently adapt energy utilization under the same conditions. This disturbance in energy metabolism may have impacts on energy-consuming processes in PP which may contribute to the markedly reduced cognitive reserve in PP. In human beings, PP approximately poorly educated people found to be prone to sporadic Alzheimer disease.

Adenosine Triphosphate↗
PubMed2004

Drug and alcohol use among patients admitted to a Danish trauma centre: a prospective study from a regional trauma centre in Scandinavia.

OBJECTIVES: The incidence of drug and alcohol use is unknown among Danish trauma patients, and has not been thoroughly investigated in Europe. METHODS: Patients admitted to the regional trauma centre in Aarhus, Denmark, were prospectively screened by blood and urine tests for the presence of alcohol, and legal and illicit drugs. The correlation with the Injury Severity Score, hospitalization time, and mortality after drug or alcohol intake was investigated. RESULTS: A quarter of all patients admitted in 1999 and 2000 had an alcohol level exceeding the national legal driving limit of 50 mg/dl, and one or more drugs were found in one in five patients. The presence of any drug or alcohol correlated positively with the Injury Severity Score, whereas alcohol level, hospitalization time, and mortality did not correlate. CONCLUSION: The rate of trauma patients with a blood serum level of alcohol greater than 100 mg/dl was similar to a previous European study and to US studies. The prevalence of drugs was less, and benzodiazepines were the most used group of drugs in our study. The routine screening of Danish trauma patients in order to implement preventative measures may be beneficial.

Alcohol Drinking↗
PubMed2003

Gene expression profile in streptozotocin rat model for sporadic Alzheimer's disease.

Sporadic Alzheimer's disease (SAD), a progressive neurodegenerative disease, is the most common cause of dementia. The etiology of the disease is still unknown, but it is suspected to be a concert of genetic and environmental factors. Intracerebroventricular injection of streptozotocin (STZ), which inhibits insulin receptor function, develops long-term and progressive deficits in learning, memory and cognitive behavior as well as biochemical changes and neuronal degeneration in rats similar to SAD. Micro-array analysis provides a genome-wide, non-biased study of gene expression patterns. The aim of this study was to investigate the gene expression pattern in the STZ animal model for SAD. RNA from rat cortex, striatum and cerebellum were analyzed for gene expression pattern via Affymetrix neurobiology chip-array and confirmed by real-time RT-PCR. Genes such as potassium channels, GABA receptors and glutamate transporter were up regulated, while insulin-like growth factor receptor was down regulated in STZ rats. These pathways may reveal molecular events causing the neuronal death in SAD.

Alzheimer Disease↗
PubMed2003

Malaria dipsticks beneficial for IMCI in Cambodia.

OBJECTIVES: The Integrated Management of Childhood Illness (IMCI) approach and new clinical treatment guidelines to control malaria among children less than 5 years old were introduced recently in Cambodia. This study was conducted to finalize the malaria part of the national IMCI fever chart. METHODS: A total of 323 sick children 2-59 months old were studied at rural health centres in northern Cambodia from February to April 2000. Cases with fever (by axillary temperature or history) or anaemia (by palmar pallor) were tested with dipsticks for Plasmodium falciparum and Plasmodium vivax in high and low malaria risk areas and, if positive, treated with anti-malarials. RESULTS: The draft IMCI chart identified children with malaria safely and effectively (sensitivity 14 of 15, approximately 93% and specificity 292 of 308, approximately 95%). The study confirmed the potential of malaria dipsticks as a part of IMCI case management. CONCLUSION: The Cambodian Ministry of Health will use the studied malaria chart during the Early Implementation Phase of IMCI. Dipsticks able to detect P. falciparum and P. vivax with high sensitivity and acceptable cost will be needed for this purpose. To promote the rational use of dipsticks, the National Centre for Malaria Control, Parasitology and Entomology (Centre National de Malaridogie, Parasitologie et Entomologie, CNM) should list all known malaria risk areas in the country and prepare detailed local maps guiding case management especially in transitional zones.

Anemia↗
PubMed2003

Memory function and brain glucose metabolism.

Memory formation and memory retrieval are subject to complex cellular and molecular processes. Increasing evidence exists that neuronal glucose metabolism and its control by the insulin signal transduction cascade are the main players in such processes. Acetylcholine synthesis depends on the availability of acetyl CoA, provided from glucose breakdown, and insulin, which controls the activity of acetylcholine transferase. ATP is necessary for both synaptic activity and plasticity. This is also true for APPs, the secreted derivative of APP. Trafficking of the latter protein is controlled by insulin and insulin receptor function also acting on activity-regulated cytoskeleton-associated gene expression, which induces biochemical stimuli involved in synaptic activity and plasticity. Any damage in neuronal glucose metabolism and its control may, therefore, cause disturbances in memory function--as is found for example in sporadic Alzheimer's disease. Mimicking these metabolic and behavioral abnormalities in experimental animals, it was found that EGb 761 (definition see editorial) shows beneficial effects both on brain glucose and energy metabolism and on behavior.

Amyloid beta-Protein Precursor↗
PubMed2003

[Pathomechanisms and hypothesis-guided therapeutic strategies for late-onset Alzheimer's disease].

Even though the clinical effectiveness of the presently used pharmaceutical therapy of sporadic Alzheimer Disease seems to be proven sufficient, their effective mechanisms are much less known or are disregarded in the evaluation of the clinical effects. However, it seems to be inevitable to know both clinical effect and effective mechanisms of pharmaceutics in order to be able to judge their adversity and benefit. In reference to the pharmaceutics implemented on sporadic AD in Germany, total different effective mechanisms are shown. In consideration of the shown pathomechanisms which have been recognized for sporadic AD, therapeutic rationales on application of Ginkgo biloba extract (EGb 761) and Memantine are evident. The application of acetylcholinesterase inhibitors, often looked on as agent of choice, is to be considered critically because of the danger of the occurrence of myopathological dysfunction, resp. the Gulf War Syndrome. Sophisticated and hastily advertised therapy strategies with statins or vaccination against beta A4 should not be used because of a lack of sufficient evidence based on the pathophysiological pattern of damage as known in sporadic AD. Future development must take in account that with sporadic AD aging influences cannot or can hardly be influenced. Therapeutic goals should consist to improve the cellular energy status and the membrane functioning.

Aging↗
PubMed2002

[Etiologic and pathogenetic heterogeneity of Alzheimer disease].

The present review discusses whether the clinically and pathologically uniform phenotype of Alzheimer's disease (AD) consists of different subtypes with respect to etiopathogenesis. In a minority of patients with AD, the disease is determined by mutations of genes on chromosomes 1, 14, and 21. The amyloid cascade hypothesis provides a conclusive model for etiopathogenesis of these cases. The majority of patients, however, suffer from the sporadic subtype of AD, the etiopathogenesis of which is presently unknown. This subtype's pathogenesis is determined by a cascade of events, among which age, a disturbance of neuronal insulin receptor function leading to a deficit in acetylcholine and available energy, and membrane instability are the most important factors. The effects of these factors are modulated by the presence or absence of apolipoprotein E4. Thus, the development of this form of AD is characterized by dynamic cellular biological changes in the brain which are independent of the metabolism of the amyloid precursor protein and genetic factors. Therefore, the sporadic subtype of AD may be regarded as an age-associated metabolic disease of the brain.

Aged↗
PubMed2002

The brain insulin signal transduction system and sporadic (type II) Alzheimer disease: an update.

Nosologically, Alzheimer disease may not be considered to be a single disorder in spite of a common clinical phenotype. Only a small proportion of about 5% to 10% of all Alzheimer cases is due to genetic mutations (type I) whereas the great majority of patients was found to be sporadic in origin. It may be assumed that susceptibility genes along with lifestyle risk factors contribute to the causation of the age-related sporadic Alzheimer disease (type II). In this context, the desensitization of the neuronal insulin receptor similar to not-insulin dependent diabetes mellitus may be of pivotal significance. This abnormality along with a reduction in brain insulin concentration is assumed to induce a cascade-like process of disturbances including cellular glucose, acetylcholine, cholesterol, and ATP associated with abnormalities in membrane pathology and the formation of both amyloidogenic derivatives and hyperphosphorylated tau protein. Sporadic Alzheimer disease may, thus, be considered to be the brain type of diabetes mellitus II. Experimental evidence is provided and discussed.

ATP-Binding Cassette Transporters↗
PubMed2002

ATPases of synaptic plasma membranes from hippocampus after ischemia and recovery during ageing.

Plasticity and relationships between individual ATPases linked to energy-utilizing systems of hippocampus, a very sensitive functional area to both age and ischemia, were studied during ageing on synaptic plasma membranes of 1-year-old "adult" and 2-year-old "aged" rats after 15 min of complete cerebral ischemia and different reperfusion times (01, 24, 48, 72, and 96 h). Activities of Na+, K+, Mg(2+)-ATPase, Mg(2+)-ATPase ouabain insensitive, Na+, K(+)-ATPase, "direct" or "basal" Mg(2+)-ATPase, and acetylcholinesterase (AChE) were evaluated in synaptic plasma membranes, where they play the major role in the regulation of presynaptic nerve ending homeostasis. This in vivo study of recovery time-course from 15 mins of cerebral ischemia indicated specific biochemical assessments of functional meaning: (a) Na+K(+)-ATPase of synaptic plasma membranes in adult and aged animals is stimulated by ischemia; (b) this "hyperactivity" is more markedly related to adult than to aged animals; (c) these abnormalities still persist after 72 and 96 h during the recirculation times, indicating the delayed postischemic suffering of the brain; (d) specific Mg(2+)-ATPase enzyme system possess a lower catalytic power in aged animals than in adult ones, but remained unaltered in adult animals by ischemia and reperfusion; (e) Mg(2+)-ATPase is stimulated in aged animals by ischemia, further increasing during reperfusion up to 72-96 h, indicating the delayed hyperactivity of hippocampus; (f) the increased metabolic activity of hippocampus is indicated by the increased activity of cholinergic system; (g) integrity of synaptic plasma membranes seems not to be altered by 15 min ischemia to a critical extent to compromise their catalytic functionality during reperfusion; (h) AChE activity increases in both adult and aged at some survival times. There are logical reasons for the hypothesis that the modifications in ATPase's catalytic activities in synaptic plasma membranes, which have been modified by ischemia in presynaptic terminals, may play important functional role during recovery time in cerebral tissue in vivo, especially as regards its responsiveness to noxious stimuli, particularly during the recirculation period from acute (or chronic) brain injury.

Aging↗
PubMed2001

Effect of Ginkgo biloba extract (EGb761) on glucose metabolism-related markers in streptozotocin-damaged rat brain.

To reveal whether an extract of Ginkgo biloba (EGb761) may affect streptozotocin (STZ)-induced impairments in brain glucose metabolism, autoradiographies of [3H]cytochalasin-B binding to the total population of glucose transporters, [125I]insulin binding to insulin receptors, [3H]glyburide binding to sulfonylurea receptors, and radioactive in situ hybridization for GLUT3 mRNA were carried out in hippocampal brain sections of adult rats that have additionally been divided into good performers (GP) and poor performers (PP) by behavioural tests before the experiments. The STZ-induced increases in hippocampal [3H]cytochalasin-B binding to (total) glucose transporters returned to almost normal values following EGb761 treatment, regardless of the experimental animal group (GP or PP) tested. Similarly, the STZ-mediated enhancements in hippocampal insulin receptor binding of GP rats were partially compensated by the treatment with EGb761. The data suggest beneficial effects of EGb671 on impaired brain glucose metabolism, at least under the experimental conditions used in the study presented.

ATP-Binding Cassette Transporters↗
PubMed2000

Increase in vulnerability of middle-aged rat brain to lead by cerebral energy depletion.

The neurotoxic effects of low-level lead (Pb) during senescence are increasing interests of importance. We investigated the effects of low-level Pb on the brain in a normal condition and a pathophysiological condition of energy shortage that is commonly found in age-related neurological diseases. Middle-aged rats (15 months old) were exposed to 200 mg/l Pb acetate in drinking water for 2 months and thereafter received bilateral intracerebroventricular injections of streptozotocin (STZ). After 1 month's additional exposure to the same level of Pb solution as before the rats were sacrificed. Blood and brain Pb levels were measured by graphite furnace atomic absorption spectrophotometry. Energy-rich phosphate levels in the brain were determined by high-performance liquid chromatography equipped with a UV detector. Astroglial activation and glucose-regulated protein (GRP)94 expression were examined immunohistochemically. Exposure to Pb increased the blood Pb level to 10.8 microg/dl and the brain Pb level to 0.052 microg/g. But a significant additional increase in the brain Pb level, to 0.101 microg/g, became obvious in rats treated with Pb + STZ. Both Pb and STZ induced perturbation in brain energy metabolism, but no further alteration in energy metabolite levels was found in rats treated with Pb + STZ. Astroglial activation and GRP94-positive astrocytes and neurons were found only in the brains of Pb + STZ-treated rats. These results suggest that exposure to low-level Pb can perturb brain energy metabolism and the brain becomes more vulnerable to Pb when it is under energy stress.

Adenosine Diphosphate↗
PubMed2000

Chronic exposure to low-level lead impairs learning ability during aging and energy metabolism in aged rat brain.

The neurotoxic effect of chronic exposure to low-level lead (Pb) with advancing age is becoming an important social issue of public health. To examine the effects of low-level Pb treatment on behavior, cognition and brain energy metabolism in aging, we administered 200 ppm Pb acetate to adult (10-month-old) male Wistar rats for 12.5 months. After 12.5 months' exposure, the mean Pb levels in blood and brain had increased to 17.5 µg/dl and 0.07 µg/g, respectively, and the rats showed impaired learning and memory functions in a holeboard spatial memory test. No significant difference was found between experimental and control groups in locomotor activity and passive avoidance tests. By HPLC analysis of energy-rich phosphate concentrations, mild abnormalities were found in parietotemporal cortex and hippocampus, but only the 4.4% decrease of ATP in the parietotemporal cortex was statistically significant. These results suggest that chronic exposure to Pb during aging stage may selectively impair learning and memory functions and may cause slight cerebral energy impairment.

Journal Article↗