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S Hoyer

Publications and source records attributed to S Hoyer.

159 records · Page 9Linked to original sources
PubMedDate not supplied

Short-term mental activation accelerates the age-related decline of high-energy phosphates in rat cerebral cortex.

Aging in rats is associated with a significant decline in brain levels of energy-rich phosphates, including ATP and creatine phosphate. To test the effects of transient mental activity mediated by psychometric testing, and of metabolic inhibition of pyruvate dehydrogenase (PDH) (an enzyme complex that generates acetyl coenzyme A (CoA) to feed the mitochondrial tricarboxylic acid cycle), we compared adult (52 to 64-week-old) and aged (104-week-old) rats with and without intracerebral injections of the PDH inhibitor, bromopyruvate (BP), in the presence and in the absence of extensive psychometric testing by standard passive avoidance and hole board test paradigms. As compared with mental rest, short-term mental activation was associated with higher levels of energy-rich phosphates in the cerebral cortex of both adult and aged animals, but did not prevent the age-dependent decline in these phosphates. ATP turnover was markedly increased by mental activity, but was less pronounced in aged animals. In the hippocampus, less marked changes in the energy pool became obvious. The abnormalities in energy metabolism indicate an age-dependent and stress-accentuated reduction of the capacity to meet such energy-dependent demands as mixed function oxidation in the aged brain. BP did not change brain levels of energy-rich phosphates, indicating that the damage caused by decreased PDH activity can be compensated for both in adult and in aged animals.

Journal Article↗
PubMedDate not supplied

Desensitization of the neuronal insulin receptor: a new approach in the etiopathogenesis of late-onset sporadic dementia of the Alzheimer type (SDAT)?

Even in its incipient stage, late-onset sporadic dementia of the Alzheimer type (SDAT) is characterized by an abnormal reduction in brain glucose consumption and energy formation. Gathering evidence indicates that cerebral glucose metabolism is controlled by brain insulin/insulin receptors. This led us to hypothesize that the abnormal reduction in glucose utilization found in Alzheimer brains is preceded by a desensitization of cerebral insulin receptors which might be due to enhanced levels of stress factors such as cortisol and catecholamines. The hypothesis is supported by clinical findings of an abnormal response to the oral glucose tolerance test in AD patients. Furthermore, experimental desensitization of the cerebral insulin receptor resulted in both cognitive deficits and metabolic abnormalities in cerebral oxidative glucose metabolism resembling those described in incipient late-onset SDAT. Glucose is the major source of energy in the CNS, and any impairment in cerebral glucose oxidation can be expected to result in deficits in both acetylcholine synthesis and ATP formation, which might contribute to altered APP processing and enhanced susceptibility to neurotoxicity.

Journal Article↗
PubMedDate not supplied

Ischemia and aging brain. Studies on glucose and energy metabolism in rat cerebral cortex.

Age has been considered to be a crucial risk factor for brain ischemic insults and their mortality. Brain ischemia has been found to cause severe abnormalities in glucose metabolism, energy metabolism and related metabolism, thus damaging the structure and function of brain cells. To study the effect of age and ischemia on brain glucose and energy metabolism, investigations were performed on one-and two-year-old male Wistar rats, the latter of which can be designated as aged. In both age groups, ischemia resulted in a depletion of glucose, OAA, ATP AND CRP, a diminution of Pyr, Citr and alpha-Keto and an accumulation of FDP, Lact, Succ, ADP and AMP in brain cortex. During ischemia, differences between the two age groups became most obvious in the concentrations of Glu, FDP, DHAP, Lact, Succ, Mal, ADP and AMP. In general, the metabolic changes in both age groups point to an increased glycolytic flux which may be less accelerated in the aged group, to an inhibition of the starting reactions of the tricarboxylic acid cycle more severe in aged animals, to a preponderance of anaplerotic reactions in this oxidative system more pronounced in the two-year-old group and to a loss of AMP in the same age group. The age-related metabolic variations measured may indicate that with age the biological plasticity of the brain may be reduced to meet emergency conditions.

Adenine Nucleotides↗
PubMedDate not supplied

Delayed decrease of excitatory amino acid neurotransmitters in parietotemporal cortex and hippocampus after complete cerebral ischemia in aged rats.

A 15-min period of complete cerebral ischemia (CCI) was used in aged rats to investigate changes in tissue contents of the amino acid neurotransmitters (AANT) glutamate (glu), aspartate (asp), gamma aminobutyric acid (gaba) and glycine (gly) in parietotemporal cortex and hippocampus during ischemia and up to 96 h of postischemic recirculation. The AANT were determined by HPLC. The excitatory AANT glu and asp showed a first decrease at the end of CCI in hippocampus and after 1 h of postischemic recirculation in parietotemporal cortex, reflecting a release of these AANT into the extracellular space with a further loss into the blood. A second decrease in glu and asp was seen after 24 h of postischemic recirculation in hippocampus and after 48 h in parietotemporal cortex. This coincides with previously described disturbances in energy metabolism from 24 h to 96 h in hippocampus and from 48 h to 72 h in parietotemporal cortex in the same experimental model in aged rats. This might be a causal factor in delayed postischemic neuronal damage. A comparison with investigations in young animals reveals an enhanced decrease of glutamate and aspartate tissue contents during the postischemic recirculation period in old rats indicating an enhanced release of these amino acid neurotransmitters. A significant decrease of gaba tissue content seen in hippocampus at 48 h and 72 h of postischemic recirculation with subsequent disproportion of inhibitory AANT (lower) to excitatory AANT (higher) might reflect a greater vulnerability of hippocampus than of parietotemporal cortex to ischemia. A significant decrease in the NMDA-receptor coactivator gly in parietotemporal cortex at the end of CCI and at 48 h, 72 h, and 96 h of postischemic recirculation, which was not seen in hippocampus, might be another reason for higher vulnerability of hippocampus to ischemia.

Journal Article↗
PubMedDate not supplied

Brain oxidative energy and related metabolism, neuronal stress, and Alzheimer's disease: a speculative synthesis.

A reduction in the cerebral metabolic rate of glucose is one of the most predominant abnormalities generally found in the Alzheimer brain, whereas the cerebral metabolic rate of oxygen is diminished only slightly or not at all at the beginning of this dementive disorder. From the cerebral metabolic rates of oxidized glucose and oxygen, the cerebral adenosine triphosphate (ATP) formation rate was calculated in incipient early-onset, incipient late-onset, and stable advanced dementia of the Alzheimer type (DAT). A reduction in ATP formation by various amounts was found, ranging from at least 7% in incipient early-onset DAT, from around 20% in incipient late-onset DAT, and from 35% up to more than 50% in stable advanced dementia. The cerebral diminution in energy availability, along with a loss of functionally important amino acids, ammonia toxicity, supposed membrane damage, dysregulation of Ca2+ homeostasis, and glycogen accumulation in the incipient stages of DAT are assumed to be stress-related abnormalities capable of inducing the formation of heat shock proteins. These events may lead to an enhanced generation of amyloid precursor protein in earlier states of DAT. If abnormally cleaved, amyloid A4 protein may be produced in increased amounts. From the results discussed in this article it is deduced as a speculative synthesis that perturbations in brain oxidative energy and related metabolism may precede the generation of amyloid precursor protein and the formation of plaques in the brain affected by incipient DAT.

Acidosis, Lactic↗
PubMedDate not supplied

[Age as a risk factor for the development of dementias? Consideration of changes in cerebral glucose metabolism with increasing age].

Based on changes in glucose and related brain metabolism in aging, it is discussed whether or not age is a risk factor for dementia. Normal brain function is tightly coupled with the availability of sufficient amounts of ATP which is normally formed from the oxidation of glucose only. The glycolytic and oxidative cerebral glucose metabolism is controlled by various mechanisms. Glucose breakdown also contributes to the formation of the neurotransmitters acetylcholine, glutamate, aspartate, and GABA. ATP yields the basis for the maintenance of neuronal homeostasis via ion homeostasis, integrity of cellular components, and intracellular transportation processes. It is also necessary for the formation of several neurotransmitters and neurohormones. Normal cerebral aging is associated with an incipient perturbation in cerebral glucose and related metabolism causing an energy deficit and thus an imbalance of cell homeostasis beyond the seventh or eighth decade of life, pointing to a threshold phenomenon. Such processes may begin insidiously, but may be assumed to progress exponentially in a self-propagating manner. These events markedly reduce the biological plasticity of the brain which may become abnormal after cerebral stress situations such as ischemia, etc. Thus, the increasing damage of neuronal homeostasis may give rise to the assumption that age, or several age-related metabolic abnormalities at the cellular level, may be regarded as risk factors for dementia.

Aged↗
PubMedDate not supplied

[Psychometric aspects of age-related changes in attention--demonstration in a rat].

Knowledge of human brain functions can often be obtained from psychobiological experiments carried out with animals. Lack of specification and sensitivity of the applied psychometric procedures may occasionally considerably limit the quality and degree of interpretation of the obtained results. The test here described is the first to offer the possibility of isolated quantitative identification of sensory and cognitive attention. It demonstrates the age-related effects on behavior-controlling attention functions in rats. What is assumed to be a general impairment of cognitive function in old age, might possibly turn out to be secondary effects of primarily altered attention thresholds.

Aging↗
PubMedDate not supplied

[Interdisciplinary research strategies in geriatric psychiatry--studies and results in dementia and depressed patients].

Eighty-one patients (mean age: 66 +/- 9 years) who had been in gerontopsychiatric in-patient care were included in the study. As well as physical, psychiatric and neurological examinations, EEG, brain CT scanning and the determination of the Ischemic Scale were performed, in order to confirm the clinical diagnosis of dementia of Alzheimer type (DAT), dementia of vascular type (DVT) or multi-infarct dementia (MID), and depression in old age, as based on the DSM III criteria. A comprehensive psychological test battery was administered, to one section of the subjects. Our results indicate that EEG and Ischemic Score can differentiate patients with DAT and DVT to a satisfactory degree, whereas CT findings and psychometric assessment were apt to confirm the overall diagnosis of dementia (DAT/DVT) and depression. Patients with dementia showed memory impairment to a greater extent than depressive patients, as could be proved by a memory test (Syndrom-Kurztest). However, a dementia screening test (Information-Memory-Concentration Test) could more accurately differentiate dementia and depression. The application of a comprehensive psychometric testing procedure did not prove to be an effective diagnostic tool in the assessment of various stages of dementia. Short dementia tests and rating scales seem to be appropriate to distinguish depression from dementia, especially in cases of mild to moderate dementia. In patients with very mild and insignificant organic brain disturbances these screening methods fall short of diagnostic validity. Beyond this, there is a current need for assessment instruments in the evaluation of alterations in personality and affectivity, such as are seen in depression.

Aged↗
PubMedDate not supplied

[Biologic plasticity of the aging brain].

The study was performed to elucidate whether the biological plasticity of the brain is reduced with advancing age. Both glucose and energy metabolism in the brain cortex of male Wistar rats aged 6, 12, 24 and 30 months were investigated under normal conditions and in 12 and 24 months old rats under complete cerebral ischemia. Under physiological conditions, glucose, fructose-1,6-phosphate and ATP decreased from 6 to 12 months of age whereas pyruvate, malate and creatine phosphate fell from 12 to 30 months of age. It was concluded that glucose and energy metabolism in brain cortex may be slightly reduced with normal aging. Complete cerebral ischemia caused server reduction in cortical glucose, pyruvate, citrate, alpha-ketoglutarate, malate, oxaloacetate, ATP and creatine phosphate and an increase in fructose-1,6-phosphate, lactate, succinate and AMP. Differences between 12 and 24 month old animals became obvious. It is concluded that aged animals as compared to adult animals are not capable of reacting sufficiently to stress conditions. The biological capacity of the brain is assumed to be reduced with aging.

Aging↗
PubMedDate not supplied

[Brain research in Germany from the gerontologic viewpoint. Problem status and international comparison].

Well-documented epidemiological studies unequivocally demonstrated that dementia rapidly increases with advancing age, producing a number of personal, family, medical and socioeconomic problems in the highly developed countries, West Germany included. Therefore, brain research in gerontology should concentrate on dementia research. International endeavors in dementia research are reported and compared with those undertaken in West Germany. Whereas dementia research has for some time been receiving major support either from scientific institutions or the government in countries such as USA, UK, France and Italy, it has not become a central topic of interest in West Germany.

Aged↗
PubMedDate not supplied

[Possibilities and limits of therapy of cognition disorders in the elderly].

Pharmacological treatment of patients suffering from sporadic late-onset dementia of Alzheimer type (DAT) is controversely discussed, omitting the fact that this age-related most frequently occurring DAT form is based on a heterogenous pathogenesis, but forms a rather uniform clinical phenotype. Furthermore, sporadic late-onset DAT is influenced in two different ways, 1) by the aging process, and 2) by the disease process itself. In this context, changes in brain glucose/energy metabolism, maintenance of calcium homeostasis, and membrane stability are discussed. It is concluded that some nootropic drugs such as dihydroergotoxine, Ginkgo biloba, nicergoline, nimodipine, piracetam, and pyritinol-HCI, registered in FRG, exert a positive effect on the clinical phenotype in approximately 30% of treated cases being in an incipient state of the disease. This effect has not been proven for advanced states. There is clear evidence that Ginkgo biloba acts on membrane lability, nimodipine on the maintenance of calcium homeostasis, and both piracetam and pyritinol-HCI on glucose/energy metabolism. These diverse effects on different underlying pathogenetic abnormalities can be assumed to be the reason why only subgroups of patients respond to the treatment with nootropic drugs.

Aged↗