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S Hoyer

Publications and source records attributed to S Hoyer.

At least 73 records · Page 4Linked to original sources
PubMed1993

Effects of long-term recovery from transient cerebral ischemia in rat brain: tissue levels of acetylcholine, monoamines, and their metabolites.

Concentrations of acetylcholine and the monoaminergic neurotransmitters dopamine, serotonin and their respective metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 4-hydroxy-3-methoxy-phenylacetic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA) and choline were simultaneously determined in the corpus striatum of rats after 15 min. complete cerebral ischemia (CCI) and in different intervals (1, 24, 48, 72, 96 hours) of postischemic cerebral reperfusion. Results were compared to respective sham-operated control animals. After 15 min. CCI acetylcholine concentration decreased to 15%, and dopamine concentration to 56% of the control values. The metabolite levels of DOPAC decreased to 40% and HVA to 64% of the control values. Acetylcholine, dopamine, serotonin and choline concentrations were not changed significantly after reperfusion. The metabolites HVA and 5-HIAA showed their maximum increases after 1 and 24 hours of reperfusion, additionally HVA was decreased both, after 72 and 96 hours of reperfusion. The data indicate that surprisingly little permanent damage could be caused by a 15 min. ischemia in the striatum. Tissue levels of the neurotransmitters appeared differentially altered but similarly regulated during ischemia and subsequent recirculation. Acetylcholine and dopamine levels decreased profoundly during ischemia. However, acetylcholine levels could be compensated rapidly during reperfusion, whereas the dopaminergic system showed a long-lasting change in its turnover rate. Although serotonin levels were unaffected by CCI, there was an increase of its presumed turnover rate during reperfusion.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Sporadic dementia of Alzheimer type: role of amyloid in etiology is challenged.

Alzheimer's disease is a heterogeneous neurodegenerative disorder. Whereas only a minority is due to genetic abnormalities and mostly with early onset, the majority of all Alzheimer cases is sporadic and with late onset. Therefore, in the latter, age-related disturbances in cellular metabolism may come into focus with respect to the etiopathogenesis rather than the primary formation of amyloid. In this "Editor's note for debate", the role of amyloid as a causative factor of sporadic Alzheimer's disease is challenged. Instead, as a possible primary abnormal event in sporadic Alzheimer's disease, the perturbations in neuronal glucose metabolism and the subsequent ATP deficit with its impacts on the secondary amyloid formation are discussed to open a new field of research and another aspect for debate.

Alzheimer Disease↗
PubMed1993

Intermediary metabolism disturbance in AD/SDAT and its relation to molecular events.

1. Early-onset dementia of Alzheimer type (EODAT; AD) and late-onset dementia of Alzheimer type (LODAT; SDAT) are heterogenous in origin. 2. A common superordinate pathobiochemical principle in the etiopathogenesis of both types of dementia is neuronal energy failure with subsequent abnormalities in cellular Ca2+ homeostasis and glucose-related amino acid metabolism. 3. These metabolic abnormalities are assumed to occur first at axodendritic terminals of the acetylcholinergic-glutamatergic circuit and to cause morphological damage at synaptic sites. 4. Metabolic stress and structural damage at synaptic sites may induce enhanced formation of APP and its cleavage product amyloid. 5. Energy-metabolism related abnormalities along with functional and structural changes at synaptic sites of the acetylcholinergic-glutamatergic circuit may precede the formation of amyloid in DAT brain.

Adenosine Triphosphate↗
PubMed1993

Action of the diabetogenic drug streptozotocin on glycolytic and glycogenolytic metabolism in adult rat brain cortex and hippocampus.

In sporadic Alzheimer's disease (AD), a number of metabolic alterations to the brain have been observed soon after the onset of the initial clinical symptoms. In particular, impairments of glucose utilization and related metabolic pathways are prominent and well-established findings in incipient AD, resembling metabolic abnormalities such as have been found in noninsulin-dependent diabetes mellitus. To mimic these abnormalities, we administered an intracerebroventricular (icv) injection of streptozotocin (STZ) to rats and studied the effects of glucose and glycogen metabolism in the cerebral cortex and hippocampus compared with controls. The enzymatic activities studied dropped significantly by 10-30% in brain cortex (cort.) and hippocampus (hc) 3 and 6 weeks after icv STZ injection: hexokinase (15% 3 weeks cort.; 14% 6 weeks cort.; 12% 3 weeks hc; 28% 6 weeks hc), phosphofructokinase (15%; 15%; 24%; 15%), glyceraldehyde-3-phosphate dehydrogenase (10%; 12%; 30%; 19%), pyruvate kinase (22%; 13%; 22%; 28%), glucose-6-phosphatase (10%; 23%; 14%; 19%) and phosphorylase a (22%; 11%; 30%; 15%). The content of glycogen was significantly higher in STZ-treated rats than in control animals (7% 3 weeks and 15% 6 weeks in cortex). In contrast to the reduced enzymatic activities, we observed no changes in the concentrations of the glycolytic intermediates glucose, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, pyruvate, lactate and glucose-1-phosphate. These data clearly indicate reduced glycolytic enzyme activity after icv administration of STZ and suggest gluconeogenesis consequent on abnormalities in glucose breakdown. This model may thus be assumed to be a useful tool to investigate pathogenetic factors involved in sporadic dementia of Alzheimer type.

Animals↗
PubMed1993

Stimulation of glycolytic key enzymes in cerebral cortex by insulin.

In adult male Wistar rats, a test was conducted to find whether or not insulin, administered intracerebroventricularly, would stimulate the activities of the glycolytic key enzymes hexokinase and phosphofructokinase in brain tissue as in non-neuronal tissue. The data clearly demonstrated an increase in these enzyme activities in cerebral cortex by approximately 20% after 80 mU insulin, whereas the increase in the hippocampus was just short of statistical significance. It is concluded that insulin controls glycolytic flux in the brain, and the suggestion that any perturbation in insulin signal transduction has severe impacts on brain glucose metabolism seems justified.

Animals↗
PubMed1993

Immunocytochemical localization of androgen receptors in human skin using monoclonal antibodies against the androgen receptor.

Androgen receptors were localized in cryostat sections of human skin using monoclonal antibodies to the human androgen receptor. Bound antibodies were detected using biotinylated rabbit anti-rat IgG, peroxidase-conjugated streptavidin, and diaminobenzidine as chromogen. In the neonatal foreskin, antibody to androgen receptor bound to keratinocytes in the epidermis and to fibroblasts and vascular endothelial cells in the dermis. Immunohistochemical staining was stronger in nuclei than in cytoplasm. This staining was specific, because there was no significant staining when antibody to the androgen receptor was replaced with IgG from nonimmunized rats or with buffer, or when antibody to androgen receptor was incubated, prior to immunostaining, with a trp E-human androgen-receptor fusion protein used as immunogen. Incubation of androgen receptor antibody with trp E alone did not affect staining. Androgen-receptor antibody also bound to keratinocytes, fibroblasts, and endothelial cells in skin from adult men and women. Skin from the scalp, nose, lip, back, and chest gave positive staining for androgen receptor. Antibody to androgen receptor also bound to the coil and ductal cells of eccrine glands, external root sheath of hair follicles, epithelium in the hair bulb, dermal papilla cells, and sebocytes. There was no significant binding to adipocytes, collagen, or stratum corneum. These results show that androgen receptor is present in cells that are known to be targets for androgens and also in cells in which the biologic effects of androgens are yet to be characterized.

Adult↗
PubMed1992

Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism.

Intracerebroventricular (ICV) injection of streptozotocin (STZ) has been reported to impair cerebral glucose utilization and energy metabolism (Nitsch and Hoyer: Neurosci Lett, 128:199-202, 1991) and also to prejudice passive avoidance learning in adult rats (Mayer et al.: Brain Res 532:95-100, 1990). It is well established that the forebrain cholinergic system, whose integrity is essential for learning and memory functions, depends on the target-derived retrograde messenger nerve growth factor (NGF). Therefore, we measured NGF and choline acetyltransferase (ChAT) activity levels in the forebrain cholinergic system in adult rats that had received a single injection of either STZ or artificial cerebrospinal fluid into the left ventricle 1 or 3 weeks prior to sacrifice. One week after ICV STZ treatment, NGF content was significantly decreased (-32%) in the septal region, where NGF-responsive cell bodies are located and NGF exerts its neurotrophic action after retrograde transport from NGF-producing targets. In contrast, NGF levels in the cortex and hippocampus, which are target regions for the basal forebrain cholinergic neurons, and in the brainstem and cerebellum were increased (+12% to +47%) within 3 weeks after ICV STZ treatment. The alterations in NGF levels were not related to changes in ChAT activity that decreased in the hippocampus by only 15%. This might be due to masking effects exerted by compensatory NGF-mediated stimulation of ChAT activity in remaining functional neurons. It is suggested that impaired behavior which has been observed after STZ-induced impairment of cerebral glucose and energy metabolism may be at least partially related to a diminished capacity of central NGF-responsive neurons to bind and/or transport NGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Age influences abnormalities in striatal dopamine metabolism during and after transient forebrain ischemia.

Age has been found to be a significant risk factor for brain ischemia and its mortality. After cerebral ischemia, the nigrostriatal dopaminergic system undergoes selective vulnerability with necrosis of striatal neurons. To study the effect of age and transient forebrain ischemia on striatal dopamine metabolism, investigations were performed in 1-year-old (adult) and 2-year-old (aged) male Wistar rats. A 15 min period of bilateral transient incomplete ischemia (ICI) was induced, and the concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA) were measured in the striatum by means of HPLC and electrochemical detection at the end of ischemia without reperfusion, and after 1 h, 24 h, 72 h, 144 h, and 288 h of postischemic cerebral reperfusion. In normal conditions, no 3-MT was detectable in either age group studied, and no other age-related changes could be found in DA or its metabolites. During ICI, an age-related difference became obvious in the 3-MT concentration, which was higher in aged animals. In this group, DOPAC dropped and DA turnover increased. After 1 h of postischemic reperfusion, the concentrations of DOPAC and HVA, as well as the turnover rate, had increased in both age groups, whereas an increase in the DA concentration became apparent in the adult animals only. The enhancement of the concentration of both DOPAC and HVA was more marked in adult animals than in aged ones. At 24 h of postischemic cerebral reperfusion, DA concentration was still elevated in both age groups, and HVA in the 1-year-old animals only. At 72 h of postischemic cerebral reperfusion, no differences were obvious between adult experimental animals and controls, whereas the elevated DA concentration persisted in aged animals, being higher than in the control group and in the 1-year-old rats. DA turnover was reduced. Longer periods of postischemic cerebral reperfusion were not found to be followed by any abnormalities compared with controls except for the DA concentration at 288 h (1-year-old group); nor were there any differences between the two age groups studied. The data obtained in this investigation clearly indicate age-related differences in the striatal dopaminergic neurotransmission after transient cerebral ischemia, in that in the aged brain reactions are markedly delayed after an injurious event such as ischemia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Oxidative energy metabolism in Alzheimer brain. Studies in early-onset and late-onset cases.

Reduction of 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 only slightly diminished or not at all the beginning of this dementive disorder. This metabolic abnormality may induce severe functional disturbances, obviously preceding morphobiological changes. From the cerebral metabolic rates of oxidized glucose and oxygen, the cerebral ATP formation rate was calculated in incipient early-onset, incipient late-onset and stable advanced dementia of Alzheimer type. A reduction of ATP formation was found from at least 7% in incipient early-onset, to around 20% in incipient late-onset DAT, and from 35% to more than 50% in stable advanced dementia. This approximation was adjusted to findings demonstrating diminished activities of enzymes active in glucose metabolism and formation of oxidation equivalents for ATP production from substrates other than glucose. A reduction for energy formation to the same range was found, as was also recently reported, in vivo in Alzheimer patients. From this rather theoretical point of view, a permanent loss of energy by at least 7-20% in incipient and progressively advancing dementia of the Alzheimer type may be assumed, with an increasing tendency in stable advanced dementia to around 50% energy loss. This energy deficit may have drastic impacts on brain function.

Adenosine Triphosphate↗
PubMed1992

Changes in brain monoaminergic neurotransmitter concentrations in rat after intracerebroventricular injection of streptozotocin.

The tissue concentrations of the monoaminergic neurotransmitters noradrenaline (NA), dopamine, and serotonin (5-HT) and of their major metabolites were measured by HPLC and electrochemical detection in several rat brain areas after intracerebroventricular injection of streptozotocin (STZ). NA levels were found to be decreased in the frontal cortex by 14%, in the entorhinal cortex by 18%, and in the striatum by 38%. In the entorhinal cortex, 5-HT levels were decreased by 19% and the 5-HT turnover rate, measured as the 5-hydroxyindoleacetic acid/5-HT ratio, was found to be increased by 48%. These results may be indicative of a distinct susceptibility of some neurotransmitters in certain brain areas after a more general impairment of brain metabolism by means of intracerebroventricular application of the diabetogenic compound STZ.

Animals↗
PubMed1992

[Vascular etiopathogenesis and degenerative dementias--current state of knowledge].

Dementia due to vascular and degenerative abnormalities has become more frequent with increasing life expectancy. Although the origin of both dementia types is still unknown, pathobiochemical perturbations comprising energy loss, lactic acidosis, calcium homeostasis and free radical formation have been found in both dementia types in incipient stages at the neuronal level. A therapeutic rational against these abnormalities is discussed.

Alzheimer Disease↗
PubMed1991

Local action of the diabetogenic drug, streptozotocin, on glucose and energy metabolism in rat brain cortex.

Glucose is the principal source for energy production in the brain, and undisturbed glucose metabolism is pivotally significant for normal function of this organ. Peripheral glucose metabolism is impaired by streptozotocin (STZ), which induces diabetes mellitus. In this investigation, we have studied the local effects of intracerebroventricular (i.c.v.) STZ on glucose and energy metabolism in cerebral cortex. Three weeks after one single i.c.v. administration of STZ, ATP and phosphocreatine (CrP) concentrations as well as the ATP/ADP ratio and the energy charge potential were decreased, while the concentrations of glucose and ADP were increased, in cerebral cortex. Arterial blood glucose levels were not altered by i.c.v. STZ. It is concluded that brain energy metabolism is locally impaired by i.c.v. STZ. We propose that the disturbance of brain energy metabolism by i.c.v. STZ administration may provide a model for the study of prolonged metabolic neuronal stress.

Adenosine Diphosphate↗
PubMed1991

Changes in striatal dopamine neurohistochemistry and biochemistry after incomplete transient cerebral ischemia in the rat.

To evaluate the development of striatal ischemic cell damage in relation to alterations in dopamine (DA) transmission, one year old male Wistar rats underwent a 15 min incomplete cerebral ischemia (ICI) induced by occlusion of the common carotid arteries and by hypovolemic hypotension. The animals were divided into the following experimental groups: sham operated rats, rats with ICI without reperfusion, and rats with ICI followed by 60 min, 24 h, 72 h and 144 h of recirculation. The ischemia induced striatal lesions were investigated in serial coronal brain sections, stained with cresylviolet or immunostained for dopamine and cAMP regulated phosphoprotein (DARPP-32), for tyrosine hydroxylase (TH) and for glial fibrillary acidic protein (GFAP) immunoreactivities (IR). Measurements of striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels were made on analogous experimental groups using HPLC methods. Signs of degeneration in small to medium sized neurons were already seen after 60 min of postischemic reperfusion together with slight decreases of DARPP-32 IR and increases of GFAP IR. The damage continued to increase up to 144 h, and after 24 h of recirculation there were clearly defined areas of reduced DARPP-32 IR, overlapping with increased TH IR and increased GFAP IR. The levels of DA, DOPAC and HVA increased sharply after 60 min (151%, 462% and 201%, respectively) remained high after 24 h and normalized after 72 h of recirculation. The DA metabolism was high after 60 min and had already normalized after 24 h of recirculation. The increased DA metabolism in striatal nerve terminals in response to ischemic injury may reflect an early degenerative change in the DA terminals. The long-lasting increase in TH IR may to some extent represent an adaptive change in response to the disappearance of DA receptor-containing nerve cells. Based on the present findings it is possible that an increased D1 transmission in neostriatum immediately following the ischemic injury may contribute to striatal nerve cell degeneration in which an enhancement of NMDA receptor transduction may be implicated.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer type: a cross-sectional comparison against advanced late-onset and incipient early-onset cases.

Global cerebral blood flow and the cerebral metabolic rates of oxygen, CO2, glucose and lactate were studied in 11 patients aged 61-78 years who had been clinically diagnosed as suffering from incipient late-onset dementia of the Alzheimer type (DAT), and in 7 patients aged 66-83 years, in whom advanced late-onset DAT had been diagnosed, using the Kety-Schmidt technique. In incipient late-onset DAT, the predominant abnormality was a 45% reduction in cerebral glucose utilization, whereas cerebral blood flow and the cerebral metabolic rate of oxygen were diminished by only 17% and 18%, respectively. A severe imbalance between oxygen utilization and glucose utilization thus became obvious. In contrast, in advanced stages of late-onset DAT, this imbalance between oxygen and glucose utilization rates in the brain became smaller and smaller, and cerebral blood flow diminished markedly; these biological brain parameters finally all settled down at between 55% and 65% of the corresponding control values. The predominant abnormality in brain glucose utilization in incipient late-onset DAT may be associated with an impairment of its control mechanism(s), which are assumed to be either an influence of brain insulin action, or brain insulin receptor function, or both.

Aged↗
PubMed1991

Abnormalities of glucose metabolism in Alzheimer's disease.

In normoglycemic patients with either incipient early-onset or incipient late-onset dementia of the Alzheimer type, the predominant disturbance consisted of a significant reduction in cerebral glucose utilization. Alterations in cerebral blood flow and oxygen consumption first occurred in late-onset dementia types. In advanced late-onset dementia, these parameters had decreased most severely. The calculated ATP production rate from glucose indicated a drastic loss of energy in all patients studied. As not all oxygen consumed by the brain was used for glucose oxidation, oxidation of substrates other than glucose (endogenous amino acids and free fatty acids) is assumed to minimize the energy loss from glucose. The possibility that the abnormalities in oxidative and energy metabolism in dementias of the Alzheimer's type are due to metabolic abnormalities in glycolytic glucose breakdown and pyruvate oxidation, rather than to an uncoupling of oxidative phosphorylation, is discussed.

Adult↗
PubMed1991

The influence of etomidate upon cerebral metabolites after complete brain ischaemia in the rat.

The influence of etomidate on post-ischaemic cerebral metabolism was examined in 1-year-old male Wistar rats. Ten rats were randomly allocated to each of three groups. Group 1 animals received etomidate for 60 min without undergoing cerebral ischaemia. In Group 2, there was a 60-min recovery period following 15 min of complete cerebral ischaemia. Etomidate was administered to Group 3 animals after 15 min of ischaemia. At the end of the study period, the brains were frozen in situ using liquid nitrogen. The cortex was then biochemically analysed. Considering glycolysis as well as the citric-acid cycle, the pattern of metabolite changes with etomidate application was almost identical to the pattern of spontaneous recovery. The content of energy-rich phosphates was reduced when Groups 2 and 3 were compared with the non-ischaemia group, indicating previous depletion of energy reserves of brain tissue. However, the energy charge as a parameter of energy balance had already been returned to normal values. We conclude that post-ischaemic application of etomidate has no favourable effect on recovery after complete cerebral ischaemia in the rat.

Animals↗
PubMed1990

Effects of changes in peripheral and cerebral glucose metabolism on locomotor activity, learning and memory in adult male rats.

Interactions of glucose and cognitive function have been reported both in the presence of elevated arterial blood glucose levels and with decreased cerebral glucose metabolism. In order to test the peripheral vs. central effects of this phenomenon, we induced irreversible hyperglycemia and depression of cerebral glucose metabolism in separate designs by means of either intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of streptozotocin (STZ), which is known to damage insulin-producing cells. Behavioral functions, such as locomotor activity, learning, and memory, were investigated under these different conditions. IP treatment with STZ decreased locomotor activity and increased initial step-through latencies on the passive avoidance test. No effects of elevated arterial blood glucose levels on retention of passive avoidance learning checked at 24 h and 144 h after training were observed. I.c.v. treatment of STZ increased the rate of locomotor activity and impaired retention in the passive avoidance test at 24 h, without further forgetfulness at 144 h. This finding may indicate disturbed acquisition and/or consolidation of memory, which may remain impaired but at a constant level, without further deterioration. Enhanced motor activity and impaired acquisition of passive avoidance learning without further impairment have also been reported as a characteristical behavioral pattern after disruption of the cholinergic system. It is therefore postulated that the observed behavioral abnormalities consequent on an impairment of cerebral glucose metabolism may be suggestive of cholinergic dysfunction.

Animals↗