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S Hoyer

Publications and source records attributed to S Hoyer.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed2000

Effects of low-level lead on glycolytic enzymes and pyruvate dehydrogenase of rat brain in vitro: relevance to sporadic Alzheimer's disease?

Lead is known to be a potent inhibitor of many enzymes working in the brain, thus possibly inducing functional problems in the brain under pathophysiological conditions. Among such enzymes are those involved in glucose metabolism and energy production. We investigated the inhibitory effects of low-level lead on brain hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK) and pyruvate dehydrogenase complex (PDHc) with rat brain homogenate. PDHc was distinctively inhibited when low-dose lead acetate was added last of all (IC50 = 5 microM) to the reaction mixture. The other enzymes were completely resistant to 5 microM of lead acetate. When the homogenate was preincubated with lead acetate HK was dramatically inhibited by low-level lead acetate (1-5 microM), in a manner dependent on both preincubation time and lead concentration. However, the inhibitory effect was abolished by coincubation with its substrates, glucose or ATP. The results suggest that exposure to low levels of lead may increase the risk of cerebral hypometabolism caused by direct inhibition of specific glucose-utilizing enzymes. In this context, lead might be regarded as a risk factor in the abnormal glucose metabolism seen in some kinds of neurodegenerative disorders such as sporadic Alzheimer's disease.

Adenosine Triphosphate↗
PubMed2000

Brain glucose and energy metabolism abnormalities in sporadic Alzheimer disease. Causes and consequences: an update.

It is discussed that Alzheimer disease does not form a nosologic entity. 5 to 10% of all Alzheimer cases are due to inherited abnormalities on chromosomes 1, or 14, or 21, whereas the majority of 90-95% is sporadic in origin. Age-related changes in the composition of membranes and in glucose/energy metabolism along with a sympathetic tone in the brain are assumed to be cellular/molecular risk factors for this disease. In its pathogenesis, the desensitization of the neuronal insulin receptor similar to non-insulin dependent diabetes mellitus may be of pivotal significance. This abnormality along with a reduction in insulin concentration is assumed to induce a cascade-like process of disturbances including decreases in cellular glucose, acetylcholine, cholesterol, and ATP, associated with changes in the metabolism of amino acids and fatty acids. There is evidence that the reductions in the availability of both glucose/energy and insulin contribute to the formation of amyloidogenic derivatives and hyperphosphorylated tau protein. This may indicate that the amyloid cascade hypothesis in not valid for sporadic Alzheimer disease but that the formation of both, amyloidogenic derivatives and hyperphosphorylated tau protein is downstream the origin of this neurodegenerative disease.

Alzheimer Disease↗
PubMed2000

Successful breast-feeding as a result of a health education programme for mothers.

The present study aims to prove an improvement in breast-feeding practices in mothers who received written instructions for successful breast-feeding and had individual counselling at the time of taking this questionnaire. The instructions were based on the results of a study carried out in Slovenia in 1993 and published in the Journal of Advanced Nursing (1998), 27, 1250-1256 (Hoyer & Pokorn 1998). The variables that were then found statistically significant in the initial and continued breast-feeding became the basis of written instructions for breast-feeding. The results obtained in the new current study were compared with that basic study which included 881 mothers. This was possible because the conditions of breast-feeding between 1993 and 1995 (when the new study was launched) had not changed. The idea of baby-friendly hospital initiative (BFHI) had not yet come into force in Slovenia. The current study comprised 203 pregnant women who were first visited during their 8th month of pregnancy. In order to collect data on breast-feeding and deliver instructions, a field nurse visited each mother eight times until the completion of first year and continued to visit them every third month and for all those who were still breast-feeding after that time, until the end of the lactation period. Statistical analysis was carried out by means of SPSS statistical package and survival analysis. All mothers in the study started breast-feeding. By the end of the first month 84.7% of them were still breast-feeding, while by the end of the third month it dropped to 74.9%, and by the end of the sixth month to 45.8%. Among these, breast-feeding alone was practised in the first week by 25.7%, by the end of the first month by 16.4%, and by the end of the third month by 9.5%. All the observed parameters were better than in the basic study. The mean duration of breast-feeding was 217 days, while the longest duration was 852 days. The survival analysis showed a statistically significant difference in the duration of breast-feeding. In the current study group, mothers weaned their infants at a slower rate than in the group from the year 1993. It has been found that the written instructions as well as personal encouragement by the field nurse exerted a favourable influence on breast-feeding practices, which was taken as a guideline for our further professional work and change of standards in the field of breast-feeding promotion.

Adult↗
PubMed2000

Linear relation between cerebral phosphocreatine concentration and memory capacities during permanent brain vessel occlusions in rats.

The present study investigates the interrelation between cerebral energy state and memory capacities in a rat model of stepwise cerebral vessel occlusions. After acute and subchronic permanent vessel occlusions, cortical energy metabolites (ATP, phosphocreatine, ADP, AMP) were detected by high-pressure liquid chromatography (HPLC) analysis, and the effects on learning, memory, and cognitive behavior were evaluated using a hole-board test. The results of the study demonstrated a drastic decrease in energy-rich phosphates by 33% for phosphocreatine and by 44% for ATP after acute vessel occlusions. In addition, rat working and reference memories were strikingly decreased to about 5% of controls. In contrast, two weeks after four-vessel occlusion, the energy state was almost completely restored to control levels. However, a significant decrease in memory capacities was observed in subchronic state. In summary, this study has demonstrated a close linear relationship (p < 0.001) between an impaired cerebral energy state and brain memory dysfunction after acute and permanent cerebral four-vessel occlusion. Thus, this animal model of stepwise reduction of the cerebral blood supply may reflect some clinically relevant processes occurring during cerebrovascular and neurodegenerative diseases.

Adenosine Diphosphate↗
PubMed2000

Inhibition of the neuronal insulin receptor. An in vivo model for sporadic Alzheimer disease?

It has been hypothesized that a central even in the early pathogenesis of sporadic Alzheimer disease (SAD) is the dysfunction of the neuronal insulin receptor signal transduction. To prove this, this receptor was inhibited by a triplicate icv application of STZ. Insulin binding sites were upregulated as in SAD. With respect to glucose transport proteins, detailed investigations are necessary.

ATP-Binding Cassette Transporters↗
PubMed1999

Interrelation between cerebral energy metabolism and behaviour in a rat model of permanent brain vessel occlusion.

The present study investigates the interrelation between cerebral energy metabolism and memory capacities after acute and permanent occlusions of carotid and vertebral arteries in adult Wistar rats (n=60). Tissue ATP, phosphocreatine, ADP, AMP and adenosine concentrations were determined in rat brain by high-pressure liquid chromatography (HPLC) analysis. Lactate and pyruvate were measured spectrophotometrically. Rats underwent psychometric testing by means of a holeboard test, closed field activity, and passive avoidance behaviour. Acute cerebral ischaemia was associated with a substantial deficit in energy load (-50%). Cortical adenosine and lactate exhibited a 7- and a 10-fold increase, respectively, in concentration. After 2 weeks of four-vessel occlusion, cortical ATP and phosphocreatine showed a partial enhancement in their concentrations if compared with acute ischaemia. Consequently, energy load (micromol/g) increased from 0.59 to 1.42 in cerebral cortex and from 0.58 to 1.14 in hippocampus under conditions of acute and permanent ischaemia, respectively. While lactate was normalized, adenosine showed a 2-fold increase in its cortical concentration. All animals improved their abilities in learning, memory and cognition after a 7-day training period. Acute vessel occlusion severely decreased working memory (WM), reference memory (RM) and locomotor activity. Simultaneously, the passive avoidance test showed a significant reduction in latency time from 247+/-85 s (sham) to 145+/-132 s. The partial improvement in brain energy state was accompanied by a relative improvement in WM and RM, although both memory capacities remained significantly lower than in controls. The data of the present study demonstrate a linear relationship between cerebral energy metabolism and brain memory capacities after acute and permanent vessel occlusions in rats.

Animals↗