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Biomedical subjects

S Hoyer

Publications and source records attributed to S Hoyer.

At least 91 records · Page 5Linked to original sources
PubMed1990

Ammonia is endogenously generated in the brain in the presence of presumed and verified dementia of Alzheimer type.

The healthy, mature, non-starved brain was found to take up a small amount of ammonia on average 7.22 +/- 0.72 micrograms/100 g x min. In contrast, in patients thought to be suffering from incipient early-onset dementia of the Alzheimer type (DAT) the brain released a larger amount of ammonia on average 25.59 +/- 16.17 micrograms/100 g x min. In advanced DAT states, an average of 2.73 +/- 0.32 micrograms/100 g x min was released indicating the temporary nature of the severe loss of amino-N during the early stages of presumed DAT. Detrimental effects of endogenously formed ammonia on brain metabolism may affect the membrane potential, the excitability of neurons, and the energy metabolism. Ammonia may be assumed to be involved in the morphological changes in astrocytes and in the gliosis observed in early degeneration related to DAT. Endogenously generated brain ammonia thus may have a role in the cascade of cell damaging events in presumed incipient DAT.

Alzheimer Disease↗
PubMed1990

Changes in pyruvate dehydrogenase complex (PDHc) activity and [3H]QNB-receptor binding in rat brain subsequent to intracerebroventricular injection of bromopyruvate.

Pyruvate dehydrogenase complex (PDHc), a link between carbohydrate and acetylcholine metabolism, is a regulatory enzyme for glucose and neurotransmitter metabolism in the brain and is reduced in Alzheimer-diseased brain. To study functional consequences of an inhibition of PDHc on muscarinic receptor binding, bromopyruvate, a suicide inhibitor od PDHc, was injected intracerebroventricularly (icv) in rats. Bromopyruvate caused a reduction of PDHc activity in the 3 brain regions examined, however, reaching significance only in the cerebral cortex and the hippocampus and not in the striatum, 24 h after injection. 3, 6, and 12 weeks later, there was a normalization or transiently increased activity, respectively, of PDHc in these brain regions. No changes in concentrations of energy-rich phosphates could be demonstrated in the cerebral cortex 12 weeks after brompyruvate injection. The number of muscarinic receptors was significantly reduced in the cerebral cortex 12 weeks after injection. The data indicate that a transient reduction of brain PDHc activity in vivo is associated with a long-lasting reduction in muscarinic cholinergic receptors. Because comparable changes of PDHc and muscarinic receptors are found in dementia of Alzhemier type, the model of bromopyruvate inhibition of PDHc in rats is suggested to be useful for experimental dementia research.

Alzheimer Disease↗
PubMed1990

Brain glucose and energy metabolism during normal aging.

The mature, healthy, non-starved mammalian brain uses glucose only as a source of energy in the form of ATP, which is necessary for several metabolic processes, such as the maintenance of cellular homeostasis via ion homeostasis, maintenance of the integrity of cellular compartments, and intracellular transportation processes for the formation of several neurotransmitters, neurotransmission itself and a few anabolic reactions. Glucose breakdown contributes to the formation of the neurotransmitters: acetylcholine, glutamate, aspartate, gamma-aminobutyrate, and glycine. Normal cerebral aging is associated with an incipient perturbation in both cerebral glucose and related metabolism, that determines an energy deficit and thus an imbalance in cell homeostasis after the 7th or 8th decade of human life, indicating a threshold phenomenon. This is evidenced by morphological/morphobiological abnormalities comprising neuronal loss and structural changes. These events are thought to cause a marked reduction in the biological plasticity of the brain, which may be severely involved after additional stress situations such as ischemia, hypoxia or hypoglycemia. The age-related increasing perturbation of neuronal homeostasis may represent a stress situation capable of inducing heat shock proteins effecting gene activity. Thus, several age-related metabolic abnormalities at the cellular level, starting with a deficient neuronal glucose and energy metabolism, can be regarded as risk factors for neuronal damage and death, and hence reduced mental capacity.

Aging↗
PubMed1990

Mapping of a functional autoimmune epitope on the beta 1-adrenergic receptor in patients with idiopathic dilated cardiomyopathy.

The presence and properties of serum autoantibodies against beta-adrenergic receptors in patients with idiopathic dilated cardiomyopathy were studied using synthetic peptides derived from the predicted sequences of the human beta-adrenergic receptors. Peptides corresponding to the sequences of the second extracellular loop of the human beta 1- and beta 2-adrenergic receptors were used as antigens in an enzyme immunoassay to screen sera from patients with dilated cardiomyopathy (n = 42), ischemic heart disease (n = 17), or healthy blood donors (n = 34). The sera of thirteen dilated cardiomyopathy patients, none of the ischemic heart disease patients, and four of the healthy controls monospecifically recognized the beta 1-peptide. Only affinity-purified antibodies of these patients had a inhibitory effect on radioligand binding to the beta 1 receptor of C6 rat glioma cells. They recognized the receptor protein by immunoblot and bound in situ to human myocardial tissue. We conclude that a subgroup of patients with idiopathic dilated cardiomyopathy have in their sera autoantibodies specifically directed against the second extracellular loop of the beta 1-adrenergic receptor. These antibodies could serve as a marker of an autoimmune response with physiological and/or pathological implications.

Adult↗
PubMed1989

Cerebral excess release of neurotransmitter amino acids subsequent to reduced cerebral glucose metabolism in early-onset dementia of Alzheimer type.

A massive cerebral release of amino acids and ammonia was found in early-onset dementia of Alzheimer type. Aspartate and glycine were liberated in high concentrations, whereas glutamate remained rather unchanged. This excess cerebral protein catabolism is due to a 44% reduction in cerebral glucose metabolism. Whereas glutamate and other glucoplastic amino acids may substitute glucose, elevated aspartate may contribute to neuronal damage. The results are discussed with respect to a possible neuronal insulin/insulin receptor deficiency.

Adult↗
PubMed1989

A new psychometric test of attention-related behavior in rats; its validity in the aging process.

The ability to distinguish relevance from irrelevance has been attributed to an attention-related mechanism and may be supposed to be disturbed in aging. The reaction to low electrical stimuli which causes neither pain nor escape behavior was investigated by means of a newly developed test in adult and aged rats. The animals' reaction was classified into two different responses depending on the intensity of the electrical stimuli. The first reaction related to sensitivity, the second reaction contained two components, an orienting response and a cognition-controlled type of discriminative behavior. There was no significant difference between the amperage values of the two reactions in adult rats. With respect to aged rats, the amperage values of both reactions are significantly increased as compared with the adult rats. The sensitivity reaction and the attention-related behaviors diverged considerably. These findings show very precisely that certain behavioral reactions may decline differently or even independently with age indicating different age-related changes in the underlying neuroanatomical systems of attention. The results demonstrate the sensitivity of the test used as a model for studying some types of attention-related mechanisms in the aging process. The use of a relatively simple test of animals' reactivity to sensory stimuli may reveal changes that are critical to understanding not only of the aging brain, but of different types of brain lesions and disorders, as well as of drug treatments.

Aging↗
PubMed1988

Abnormalities in glucose and energy metabolism are more severe in the hippocampus than in cerebral cortex in postischemic recovery in aged rats.

After brain ischemia, dissimilar disturbances in morphology and energy metabolism have become evident in cortex and hippocampus the reason of which has not been completely elucidated as yet. Aged male Wistar rats underwent a 15 min complete cerebral ischemia induced by occlusion of the carotid and vertebral arteries and by hypovolemic hypotension. Thereafter, normotensive recirculation of the brain was established and the animals were allowed to recover for either 60 min, or 24 h, or 48 h, or 72 h, or 96 h. In cerebral cortex and hippocampus, the concentrations of glucose, lactate, and energy-rich compounds were measured by means of standard enzymatic methods. After ischemia, the ischemia induced metabolic abnormalities as measured as concentrations of glucose and lactate, and as energy-rich compounds normalized rapidly. After 48 and 72 h recirculation, a disturbance in glucose breakdown and an imbalance in energy metabolism became manifest in cerebral cortex, and even earlier (24 h) and longer (96 h), and more severe, in hippocampus. These changes may contribute to delayed neuronal damage and cell death in the areas studied.

Aging↗
PubMed1988

Glutamate decarboxylase-immunoreactive neurons in the aging rat hippocampus are more resistant to ischemia than CA1 pyramidal cells.

Glutamate decarboxylase (GAD)-immunoreactive, supposedly GABAergic inhibitory, neurons in various fields of the rat hippocampus and pyramidal cells in area CA1 were quantified 1 week after transient cerebral ischemia by 4-vessel occlusion. Whereas the number of CA1 pyramidal cells in Toluidine blue-stained semithin sections were found reduced by 50% when compared with controls there was no loss of GAD-immunoreactive cells in vibratome sections of hippocampus proper and fascia dentata. These data suggest that GABAergic hippocampal neurons are more resistant to ischemia than CA1 pyramidal cells.

Aging↗
PubMed1988

Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type?

Global cerebral blood flow, oxidative brain metabolism, and the cerebral arteriovenous differences of amino acids and ammonia were studied in 20 clinically diagnosed patients with early-onset dementia of Alzheimer type (DAT). Eleven healthy age-matched subjects and 15 healthy young volunteers served as controls. The most prominent abnormality in patients with early-onset DAT was a 44% reduction in the cerebral metabolic rate of glucose and a fourfold increase of lactate production, whereas cerebral blood flow and the cerebral metabolic rate of oxygen were found not to be altered. The cerebral amino-N balance substantially changed in patients with early-onset DAT, showing a massive loss of amino acids and ammonia from the brain, which was indicative of excess protein catabolism due to cell degeneration in the acutely diseased brain. The abnormality found in glucose metabolism may suggest a perturbed control of glycolytic breakdown of glucose and its first oxidation step at the pyruvate dehydrogenase complex level, this thus being of pivotal significance in early-onset DAT.

Adult↗
PubMed1987

Ischemia in aged brain.

A 15-min complete cerebral ischemia, and repetitive ischemic insults of 15-min duration each cause changes in brain cortical glucose and energy metabolism which are similar in quality but different in quantity. Abnormalities in glycolytic flux, lactate production, cessation of oxidation and energy production were found to be more pronounced with advancing age, thus indicating a reduced biological plasticity of the brain to meet emergency conditions. Repeatedly occurring ischemic insults may damage energy metabolism in particular.

Aging↗
PubMed1987

[No indications for barbiturate therapy following complete cerebral ischemia. A comment on "cerebroprotection" by barbiturates following cardiovascular arrest].

Cardiac arrest is followed by complete cerebral ischemia, which is characterized by delayed hypoperfusion and transient hypermetabolism. Brain metabolism depressant drugs, such as barbiturates, were suggested to improve neuronal outcome. The hypothesis of a cerebroprotective effect of barbiturates remained nevertheless controversial. In order to define the utility of large doses of thiopentone, the effect of thiopentone on carbohydrate and energy metabolism of 1-year old Wistar rats was investigated in an experimental model of complete reversible ischemia followed by a recovery period. No beneficial effect of high-dose thiopentone could be demonstrated by means of changes in the carbohydrate metabolism and the energyrich compounds. There were no differences between the treated group and the spontaneous recovery group. These results are mainly confirmed by other investigators. In contrast to focal ischemia and hypoxemia beneficial effects of barbiturates can not be demonstrated after complete cerebral ischemia in experimental studies and in clinical studies as well. In conclusion there is no indication for high-dose barbiturate therapy after cardiac arrest and successfull resuscitation.

Animals↗
PubMed1986

Senile dementia and Alzheimer's disease. Brain blood flow and metabolism.

Dementia of Alzheimer type is not form of accelerated aging. Blood flow, oxygen consumption and glucose utilization of the normally aged brain are maintained unchanged from the 3rd to the 7th decade of life. Thereafter, these parameters may decrease. Brain blood flow and oxidative metabolism is reduced in dementia of Alzheimer type and thus is different from the aged-matched mentally healthy subjects. There is evidence that the predominant impairment among these parameters may occur in cerebral glucose metabolism. This disturbance may precede changes in cerebral oxygen consumption and blood flow. Cerebral hypometabolism of glucose is accentuated in the temporo-parietal cortex. This finding may be helpful in diagnosing dementia of Alzheimer type.

Adolescent↗
PubMed1986

Classification as a function of the degree of dementia.

Primary dementias may be classified into dementia of Alzheimer type (DAT) and dementia of vascular type (DVT) which differ in morphological and clinical respects. Studies on cerebral blood flow (CBF) and metabolism may support the classification procedure provided the dementias are in their early phase and their symptoms are florid. Generally unchanged CBF and cerebral metabolic rate (CMR) oxygen are accompanied either by reduced CMR glucose (DAT) or by increased CMR glucose (DVT). In chronic dementias, these differences disappear and no classification of DAT and DVT by means of CBF and metabolism may be possible. As far as the degree of dementia is concerned, a close correlation between diminished CBF and metabolism and severity of dementia is generally found. However, in some cases of productive or hyperactive dementia without brain atrophy, this correlation is not evident.

Alcohol Amnestic Disorder↗
PubMed1985

The effect of age on glucose and energy metabolism in brain cortex of rats.

It is well documented that the mature human brain oxidizes only glucose to obtain energy under physiological, nonstarved conditions. Through adulthood to the beginning of senescence, the balance between oxygen and glucose consumption of the brain was found to be unchanged as the basis for energy production. Beyond the age of 70 yr, however, cerebral glucose consumption appears to decrease. In the present study, the effect of advancing age on glucose and energy metabolism in brain cortex of rats was investigated. The study was carried out in male Wistar rats, 6 (young adult), 12 (adult), 24 and 30 (both aged) mth of age. Male Wistar rats may be designated as being 'aged' from 24 mth of life onwards. Intermediates of glycolysis, tricarboxylic acid cycle and energy-rich compounds were measured by means of sensitive standard enzymatic methods under steady-state conditions of arterial normotension, normoxemia, normocapnia and normothermia in anesthesia with 0.5 vol% halothane and nitrous oxide/oxygen 70:30. The 12-mth-old adult rats served as controls. The glucose concentration in brain cortex was found to be about 1.5 times higher in 6-mth-old than in 12-mth-old animals but did not differ in the 12-, 24-, and 30-mth-old rats. Besides glucose, fructose-1,6-phosphate and ATP decreased from young adult to adult rats while pyruvate, malate and creatine phosphate diminish with advancing age. A tendency to reduction with aging was also evident in glucose-6-phosphate, fructose-1, 6-diphosphate, and lactate. The fall in substrate concentrations may be attributed to the reduced activity of enzymes acting in glucose breakdown. It is concluded that glucose and energy metabolism may diminish with the process of normal aging, but that the reduction is of only moderate extent.

Adenosine Triphosphate↗