[Conditions for the understanding of aging].
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Aged↗
Biomedical subjects
W Meier-Ruge
Publications and source records attributed to W Meier-Ruge.
Quantitative morphology of synaptic plasticity in the aging brain.
Quantitation of synaptic ultrastructural changes is of great importance in neurobiology, since merely qualitative alterations, if not extreme, are not readily detectable. In the present paper we discuss our previous and present findings on the number (numerical density: Nv), size (average length of the synaptic profiles: L) and surface contact area (surface density: Sv) of the synaptic junctions in aging rodent and human brains. We found that number and size of the synapses are in a close inverse relationship so as to maintain the total surface contact are among the nerve cells constant. These three parameters are closely related to each other, their quantitation may thus represent a reliable index of the morphological aspects of synaptic plasticity, i.e. the modification of ultrastructure occurring at synaptic membranes after transient changes in synaptic activity. During aging, the morphological plasticity of synapses appears to be seriously impaired: the number of synapses and the total surface contact area among the nerve cells are markedly reduced. However, old nerve cells seem to retain the ability to modify their synaptic endings and to partially compensate for the reduced surface density of the contact zones by expanding the average size of the persisting junctions. Our recent studies on synaptic plasticity in human brains from old and demented subjects showed that while the size of the synaptic contacts remains constant, the numerical and surface densities undergo a further decrease in demented brains relative to that in normal aging.
Adult↗
Effects of brovincamine on the stereological parameters of corticocerebral capillaries.
A number of clinical studies in patients with cerebrovascular insufficiency or symptoms resulting from multiple cerebral infarctions have shown that brovincamine significantly reduces the number of ischaemic regions and the left/right asymmetry of blood flow to the hemispheres, and brings about general improvement of the microcirculation. An optical-electronic image analysis technique was used to investigate whether brovincamine (7.5 mg/kg/day orally for 4 weeks) had any effect on stereological parameters of the corticocerebral capillaries of 1-year-old and 3-year-old OFA rats (n = 20). The older group of rats was included since in man changes in capillary geometry are known to be one of the manifestations of aging. The results show that brovincamine significantly increases the efficiency of capillary clearance, which is accompanied by an increase in capillary length and capillary volume per unit volume of tissue, resulting in a shortening of the mean intercapillary diffusion paths, a rise in capillary density and an increase in capillary diffusion area. No significant difference was observable between young and old rats. The changes in both groups of animals took the same form. From the above findings it was concluded that brovincamine improves the corticocerebral microcirculation by virtue of its effect on capillary geometry.
Age Factors↗
Effects of prolonged co-dergocrine mesylate (Hydergine) treatment on local cerebral glucose uptake in aged Fischer 344 rats.
Hydergine (co-dergocrine mesylate) was administered orally for 4 weeks to adult (10-12 months old) and aged (28 months old) Fischer 344 rats at dosages ranging from 0.1 mg to 4.0 mg/kg daily, in order to investigate its effect on 14C-deoxyglucose (DOG) uptake by the brain and the dose-effect relation. In the aged rats the dose-effect curve was bell-shaped, with maximal increases in DOG uptake at 0.6 mg/kg co-dergocrine. These were particularly pronounced in the caudoputamen (+47%), nucleus ventralis thalami (+32%), nucleus ventromedialis hypothalami (+57%) and the nucleus suprachiasmaticus (+39%), while the nucleus ambiguus, nucleus dorsalis nervi vagi, nucleus cuneatus and nucleus loci coeruleus also showed increases in DOG utilisation of between 23% and 29%. The dose-effect curve for the adult rats was similar in shape to that for the aged rats, but the peak was much lower and occurred at the lowest dosage (0.1 mg/kg). Cerebral DOG uptake responded considerably more sensitively in the adult rats than in the aged rats, so that the higher dosages were associated with a fall in DOG uptake. Parallels may be detected between the pharmacological effects exerted by co-dergocrine and its effects on DOG uptake in the nuclei of the extrapyramidal system (dopaminergic stimulation), in the hypothalamus (autonomic and neuroendocrine effects, regulation of body temperature and sleep) and in the alpha-receptor nuclei (alpha-blockade, cardiovascular regulation).
Age Factors↗
Effects of hyperinsulinism and of diabetes on proteoglycans of the intervertebral disc in weanling sand rats.
Weanling sand rats (Psammomys obesus) develop hyperinsulinemia or diabetes or both, if fed a standard laboratory diet without a supplement of fiber rich salt bush. The annuli fibrosi of hyperinsulinemic or diabetic animals, which are still hyperinsulinemic, show a slight but statistically significant increase in chondroitin sulfate and a lesser, statistically nonsignificant increase in keratan sulfate. Possible causes of these changes are discussed and the likelihood of a role of hyperinsulinism in their production is pointed out.
Animal Feed↗
Morphometric investigation of nerve cells, neuropil and senile plaques in senile dementia of the Alzheimer type.
Eight brains from patients with a mean age of 82 years showing clinical and neuropathological manifestations of senile dementia of the Alzheimer type (SDAT) and 6 control brains from individuals with a mean age of 89 years who were mentally normal or who had minimal senile impairment of memory, were selected by a rigorous elimination procedure for final evaluation from a total of 26 brains. Using an optical electronic image-analysis system, stereological measurements were made of the size and number of senile plaques, and of nerve cell area, capillary diameter, capillary length and intercapillary distance in the medial frontal gyrus, medial temporal gyrus and precentral gyrus. The number and size of senile plaques did not correlate with any of the other parameters measured, whereas Mountjoy et al. (1983) found a correlation between neuronal count and plaque count. In SDAT the cerebral cortex displayed significant atrophy of the neuronal perikarya (mean decrease approximately 50%). The greatest decrease in nerve cell area (55%) was seen in layers III and IV of the medial temporal cortex. Stereological measurements on the capillary network revealed only moderate neuropil shrinkage. Capillary volume was on average 30% greater in SDAT as a result of a decrease in intercapillary distance. These findings indicate that nerve cell shrinkage is a characteristic indicator of senile dementia. Neuropil atrophy may be of secondary importance.
Aged↗
[Ultrashort segment Hirschsprung disease. An objective picture of the disease substantiated by biopsy].
The enzyme histotopochemical characteristics of 18 cases with ultrashort Hirschsprung's disease - investigated during the past 20 years - are analysed. The aganglionic segment, having an extension of 1-3 cm, is characterised by an increase of acetylcholinesterase activity in parasympathetic nerve fibres of the muscularis mucosae. A similar increase of acetylcholinesterase in the nerve fibres of the lamina propria mucosae - as characteristic in Hirschsprung's disease - is usually absent. Strip biopsies which include mucosa of the linea dentata and the distal rectum often show the transition from the aganglionic to the innervated mucosa. To avoid a faulty diagnosis by overlooking an ultrashort Hirschsprung's disease, it is recommended to take the first biopsy from the linea dentata, and biopsies 1 cm, 2 cm and 4 cm above this level, or to conduct a strip biopsy of 1-2 cm length taken from this area. 2/3 of the cases investigated were diagnosed during the first year of life. In 1/3 of the cases the diagnosis was made in patients who were 4 to 21 years of age. The average incidence of the ultrashort Hirschsprung's disease is 10% in relation to all aganglionoses studied. In recent years, however, diagnosis of this particular rectum disease was made more often (14%) due to a better knowledge of the disease (6.8% of all investigated inborn innervation failures of the colon). Ultrashort Hirschsprung is a rare disease, although it is observed more often than total aganglionosis of the colon (Zuelzer-Wilson syndrome). The sex ratio, being 5 male male: 1 female, is within the range of Hirschsprung's disease. Hence, enzyme histotopochemical means enable substantiation of ultrashort Hirschsprung's disease as a special form of an aganglionosis of the distal rectum.
Acetylcholinesterase↗
Neurochemical enzyme changes in Alzheimer's and Pick's disease.
Neurochemical investigations of the whole temporal lobe of cases with Alzheimer's disease (n = 15); 80.7 +/- 1.7 yr), Pick's disease (n = 3; 65 +/- 1.7 yr), and age-matched controls (n = 18; 74.7 +/- 2.6 yr), demonstrate that Alzheimer's and Pick's disease are primary degenerative brain diseases. The activities of glycolytic enzymes, ATPases, carbonic anhydrase, acetylcholinesterase and protein kinase were significantly lower in Alzheimer's and in Pick's disease than in age-matched controls. Pick's disease is characterised by a more pronounced reduction of the enzymes investigated, which is considered to be an expression of a more dramatic degenerative process. The differences between Alzheimer's disease and Pick's disease are quantitative.
Acetylcholinesterase↗
[Stereomorphometric studies of capillaries and nerve cells in the normal brain of the aged subject and in Alzheimer's disease].
Stereological investigations of putamen, frontal gyrus and precentral gyrus in Alzheimer's disease and in age-matched controls were performed with an optical electronic image analysis system (Leitz). In all layers of the frontal cortex, a significant atrophy of neuronal perikarya is observed in Alzheimer's disease compared with normally aged specimen. In putamen, a non significant decrease is measured in the area of nerve cells. The morphometric results of the capillary measurements show a 40% increase of the capillary volume in the brain cortex of the Alzheimer group compared with the controls. These results which are probably localized in cortex represent gross atrophy of the frontal brain in senile dementia of the Alzheimer type. No changes of this kind can be observed in young individuals (19-45 years) or the normal aged group (85-95 years).
Adult↗
[Neuronal intestinal dysplasia. Critical 10-years' analysis of clinical and biopsy diagnosis].
61 cases of neuronal intestinal dysplasia are compared in a follow-up study. Two clinically and bioptically different types of intestinal dysplasia can be distinguished. One type with involvement of the sympathetic nerves and the clinical signs of intestinal spasticity, ulcerative colitis with haemorrhagic stools. Histotopochemically, this disease pattern shows aplasia or hypoplasia of the sympathetic nerves with enhanced parasympathetic activity (elevated acetylcholinesterase activity in the lamina propria mucosae and orbicular musculature). One type with involvement of the plexus submucosus clinically accompanied by adynamia of the colon with megacolon formation. This type becomes manifest usually around the 6th month of life. Bioptically there are large groups of ganglion cells and Schwann's cells, but there is also acetylcholinesterase activity as in the other type. This 2nd form is seen more frequently. A third form is a combination of both diseases. The incidence rate of neuronal intestinal dysplasia is equal to that of Hirschsprung's disease.
Acetylcholinesterase↗
Pharmacological aspects of gerontological brain research.
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Aging↗
Localized and disseminated forms of neuronal intestinal dysplasia mimicking Hirschsprung's disease.
Neuronal intestinal dysplasia is characterized by structural changes consisting of hyperplasia of the myenteric plexus, an increase of the acetyl cholinesterase activity and the formation of giant ganglia. The condition gives rise to signs and symptoms similar to Hirschsprung's disease. Neuronal intestinal dysplasia can occur as a clinical entity itself in a localized or disseminated form. It may also accompany Hirschsprung's disease either as a localized defect or as a disseminated disorder of the entire intestinal tract. In localized forms, resection of the entire diseased segment is curative. Disseminated forms often have a fetal outcome despite ileostomy and colectomy. It is conceivable that differences in the severity of symptoms depend upon the development or absence of sympathetic innervation.
Diagnosis, Differential↗
Neurochemical findings in the aging brain.
We studied the influence of normal aging on 13 glycolytic enzymes, ATPase, carbonic anhydrase, and protein kinase in the human brain cortex and putamen, where there is a significant increase in soluble HK activity with age. This phenomenon is considered to be the result of an increased release of HK from mitochondrial membranes. A significant negative correlation of the activity of F6PK with age is observed in brain cortex and putamen. While the regulation of glycolysis imposes a limit on the formation of ATP with increasing age, no change appears to occur in the enzymatic capacity to break down ATP. Na+/K+-ATPase and Mg++-ATPase do not change with age. Carbonic anhydrase, important in the regulation of the pO2/pCO2 ratio in the brain tissue, demonstrates a significant decline with increasing age. Thus pCO2-dependent regulation of tissue pH, ionic transport processes, and cerebral blood flow regulation have the tendency to become more and more unstable. Protein kinase demonstrates a progressive age-dependent decline in cAMP-dependent activity, which is most significant in brain cortex and thalamus, followed by hippocampus, amygdala, and globus pallidus. The enzyme is of importance for the phosphorylation of the cell membrane and is thus of functional relevance for the nerve cell.
Adenosine Triphosphatases↗
[Quantitative-morphological changes of capillaries and neurons in the aging human putamen (author's transl)].
Stereological investigations (Classimat) of the capillary net of 4 age-groups, ranging between 19 and 94 years, revealed significant increase of capillary volume and total length, and decreased intercapillary distances in the aging putamen. Neuronal size and shape measurements (Texture-Analyzer-System) of the same brain region showed significant changes between the young (19-44 y.) and oldest (85-94 y.) group, indicating senile atrophy of the neuronal perikarya. Quantitative image-analysis facilitates to evaluate new morphometrical data of the aging process in the human brain, which are important for a pharmacological concept of treating cerebral insufficiency symptoms.
Adult↗
[Capillary changes in the brain in aging men and their pathophysiological significance].
In autoptic brains of neurologically and psychiatrically healthy patients, aged between 19 and 94 years, structural changes of capillaries and neurons were stereologically investigtaed in different parts of the brain. The results of the putamen reveal a significant increase of the capillary volume and a decrease of the neuronal perikaryon area with age. The cerebral cortex shows only a slight increase of the capillary length, while the nerve cells are significantly smaller. These results lead to the assumption that a decrease of cerebral circulation in old age might be on one hand a symptom of a decreased nerve cell activity but on the other hand the results of changed stereological capillary parameters due to changes of the volume particularly of subcortical brain structures. In animal experiments with functional changes of the brain by hypovolemic oligemia, ischemia and respiratory hypoxia a correlation between electrical brain activity, oxygen consumption, microcirculation and morphometrical capillary parameters could be demonstrated.
Adult↗
Accelerated ageing or selective neuronal loss as an important cause of dementia?
Extensive biochemical analysis of whole temporal lobe from cases of dementia and controls suggests that Alzheimer's disease is a primary degenerative nerve-cell disorder and not the result of accelerated ageing. There is selective loss of neocortical cholinergic neurones. Transmitter systems apart from the cholinergic system appears to be affected, but to a lesser extent, and there are no significant changes in the caudate nucleus. The change in cholinergic neurones has been confirmed in biopsy samples.
Aged↗
Micropreparation techniques in quantitative histochemistry - density gradient centrifugation, manual microdissection and laser microbeam preparation of tissue.
Each quantitative histochemical problem needs its specific method for tissue preparation. In this connection two of the most important preparation methods, density gradient centrifugation and microdissection of freeze-dried tissue slices, are described. Density gradient centrifugation is a very effective procedure for preparative separation of cell particles such as cell nuclei. The details of the preparation of glial and neuronal cell nuclei are described. The in vitro phosphorylation of histone in the chromatin in relation to age is given as a practical example of the quantitative histochemical application to a preparation of cell nuclei. Other techniques of tissue preparation are the manual tissue microdissection according to Lowry and the Laser microbeam preparation. Advantages and disadvantages of both methods are compared. It is shown, that the introduction of Laser microbeam dissection technique, as alternative to manual microdissection, add new dimensions to Lowry's ultramicrochemical methods. One has greater freedom in the choice of the sample size and the number of samples dissected from the same slice. Furthermore, the need for a well-trained person for the preparation is eliminated. The preparation is also considerably less time consuming and easier to perform than the manual free hand preparation. Two quantitative histochemical methods used for the investigation of microdissected tissue samples are described: the gas-chromatography-massfragmentography (GC/MS)-method for determination of transmitters and its metabolites as well as the enzymatic cycling technique of Lowry. The GC/MS-method is explained with an example of noradrenaline and dopamine determination. The enzymatic cycling technique is demonstrated in combination with the Oil-Well-Technique for determination of the NADP-cycle.
Cell Fractionation↗
[The protein kinase system of the human brain: a contribution to the study of normal aging (author's transl)].
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Adult↗