A translation of Otto Binswanger's article, 'The delineation of the generalized progressive paralyses'. 1894.
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Arteriosclerosis↗
Biomedical subjects
R Nitsch
Publications and source records attributed to R Nitsch.
Area-specific morphological and neurochemical maturation of non-pyramidal neurons in the rat hippocampus as revealed by parvalbumin immunocytochemistry.
The time course of the morphological differentiation of non-pyramidal neurons in the rat hippocampus shows an area specificity. Thus, non-pyramidal neurons in CA3 appear more mature than in CA1 at early postnatal stages. Physiological data provide evidence for an earlier maturation of GABA-mediated inhibition in CA3 in comparison to CA1. As the calcium-binding protein parvalbumin (PARV) is thought to be a marker for highly active inhibitory neurons, we analyzed the area-specific appearance of PARV in GABAergic neurons during development. Employing combined light and electron microscopic immunocytochemistry, we revealed an area specificity in the time course of the neurochemical and morphological maturation of this functionally important subpopulation of non-pyramidal cells. The first appearance of PARV-immunoreactivity was observed at P7 and was exclusively located in cell bodies in CA3. At P8, neurons in CA3 exhibited PARV-immunoreactivity in cell bodies and dendrites, but very rarely in axon terminals. These neurons displayed the typical light and electron microscopic characteristics of GABAergic non-pyramidal cells. At P10, axon terminals formed typical baskets surrounding the pyramidal cells. The appearance of PARV-immunoreactivity in cell bodies, dendrites and axon terminals in CA1 was noticed about 1 to 2 days later. In the fascia dentata, non-granule cells displayed immunoreactivity not before P10. These data indicate a sequential neurochemical and morphological maturation of non-pyramidal neurons that may be related to differences in the maturation of inhibition during hippocampal development.
Animals↗
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↗
Alterations of phospholipid metabolites in postmortem brain from patients with Alzheimer's disease.
To test the hypothesis that brain cell membranes degenerate in Alzheimer's disease (AD), we measured the levels of phospholipids, their water-soluble metabolites, and glycerophosphocholine (GPC) cholinephosphodiesterase activity in postmortem brain tissue from patients with AD and age-matched controls. We found significantly higher levels of the phospholipid catabolite GPC in AD brain. In contrast, choline and ethanolamine levels were significantly lower in AD, and phospholipid levels were slightly decreased. Furthermore, in AD the activity of the GPC-degrading enzyme GPC cholinephosphodiesterase was unaltered. Our results indicate that membrane phospholipid catabolism is increased in AD brain. Inasmuch as the tissue levels of initial phospholipid precursors were decreased, we suggest that phospholipid turnover is elevated in this neurodegenerative disease.
Alzheimer Disease↗
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↗
Proportion of parvalbumin-positive basket cells in the GABAergic innervation of pyramidal and granule cells of the rat hippocampal formation.
Recent studies have indicated that hippocampal GABAergic neurons in both the dentate gyrus and Ammon's horn contain immunoreactivity for the calcium-binding protein parvalbumin (PARV). Although the distribution of PARV-positive neurons has been previously described, detailed quantitative electron microscopic studies of the PARV-positive axon terminals in the hippocampal formation are lacking. In the present study, immunocytochemical methods were used to localize PARV-positive neurons and axon terminals to determine their similarity to GABAergic neurons. The PARV-positive cells and axon terminals are associated closely with the pyramidal and granule cell layers. In agreement with previous studies, the morphology of PARV-positive neurons is similar to that of GABAergic cells, including the basket cells of both the dentate gyrus and Ammon's horn. The PARV-positive axon terminals form exclusively symmetric synapses with somata, dendrites, dendritic spines, and axon initial segments. However, these terminals represent only a portion of the total number of terminals that form symmetric synapses. Quantitative results indicate that only 32-38% of the total number of terminals forming symmetric axosomatic synapses with principal cells of the dentate gyrus and Ammon's horn are PARV positive. Together with previous findings from light microscopic double-labeling studies, these data indicate that the PARV-positive terminals arise from a subpopulation of GABAergic hippocampal neurons. Finally, it is important to note that the terminal plexus of PARV-positive hippocampal axons overlaps at all postsynaptic sites with a plexus of PARV-negative axons.
Animals↗
Late appearance of parvalbumin-immunoreactivity in the development of GABAergic neurons in the rat hippocampus.
The calcium-binding protein parvalbumin (PARV) is supposed to have a protective function under conditions of experimental seizure and hypoxia in a subgroup of GABAergic inhibitory neurons in the adult rat hippocampus. Here we studied the appearance of PARV immunoreactivity in rat hippocampal non-pyramidal cells during postnatal development in comparison to glutamate decarboxylase (GAD) immunoreactivity. PARV-immunoreactive neurons were not observed before postnatal day 7 whereas GAD-positive neurons and terminal-like puncta were present at postnatal day 2 (P2) and were frequent around P5. From other studies it is known that all GABAergic neurons are formed prenatally. Our data thus indicate that in the early postnatal period GABAergic non-pyramidal cells are poorly protected by calcium-binding proteins against a pathological calcium influx.
Animals↗
Most somatostatin-immunoreactive neurons in the rat fascia dentata do not contain the calcium-binding protein parvalbumin.
A selective loss of somatostatin (SS)-containing neurons in the hilar region has been reported in patients suffering from temporal lobe epilepsy. Conversely, neurons containing calcium-binding proteins such as parvalbumin (PARV) are known to be very resistant under experimental seizure conditions. In this study, we analyzed the coexistence of SS and PARV in neurons of the rat fascia dentata by using serial semi-thin cryostat sections for pre-embedding immunocytochemistry. Our results show that only 5.7% of the SS-immunoreactive hilar neurons contain PARV. The data suggest that SS-containing hilar neurons are less protected against seizure-induced calcium overload than other neurons containing calcium-binding proteins.
Animals↗
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↗
Axo-axonic chandelier cells in the rat fascia dentata: Golgi-electron microscopy and immunocytochemical studies.
Synaptic transmission can be blocked very efficiently by inhibitory synapses on axon initial segments. Inhibitory chandelier cells forming synapses on the axon initial segment of pyramidal neurons have been found in the neocortex and hippocampus proper. Here we describe an axo-axonic local circuit neuron in the rat fascia dentata that establishes synaptic contacts with axon initial segments of numerous dentate granule cells. Examination of a large number of Golgi-impregnated nongranule cells in the fascia dentata of rats revealed a group of neurons with characteristics of chandelier cells. Thus these cells exhibited an extensive axonal plexus within the granular layer that characteristically formed vertical aggregations of axonal varicosities. The cell bodies of these neurons were located in the inner molecular layer or in the outer part of the granular layer. Their dendrites invaded the molecular layer, suggesting an afferent innervation similar to that of the granule cells. Well impregnated putative axo-axonic cells were gold-toned for an electron microscopic analysis. The cell bodies and dendrites of these neurons exhibited characteristic ultrastructural features of nongranule cells, i.e., large amounts of perinuclear cytoplasm, infoldings of the nuclear membrane, and a large number of synaptic contacts on the perikaryon and on the smooth dendritic shafts. The axon originating from the cell body or from a proximal dendrite gave rise to numerous vesicle-filled varicosities that almost exclusively formed symmetric synaptic contacts with axon initial segments. A semiquantitative study of five axonal complexes demonstrated that 92.3% of identified postsynaptic elements were initial segments of granule cell axons. Immunostaining with antibodies against glutamate decarboxylase (GAD) and parvalbumin (PARV) revealed a subpopulation of neurons that very much resembled the Golgi-impregnated axo-axonic cells with regard to cell body location, dendritic arborization, and fine structural characteristics of perikarya and dendrites. GAD and PARV were found to be coexistent in these cells. Moreover, we found GAD- and PARV-immunoreactive terminals in symmetric synaptic contact with axon initial segments of granule cells. The present study has shown a hitherto unknown axo-axonic cell in the rat fascia dentata. On the basis of our immunocytochemical findings, we hypothesize that this cell exerts a strong inhibitory effect on dentate granule cells. This way, signal transmission from the fascia dentata to the hippocampus proper within the "trisynaptic pathway" can efficiently be controlled by a group of highly specialized neurons.
Animals↗
The parvalbumin-containing nonpyramidal neurons in the rat hippocampus.
The calcium-binding protein parvalbumin is considered to be involved in the control of intracellular ion homeostasis of highly active inhibitory neurons. A review of the light and electron microscopical features as well as the identified synaptic connections of these neurons is presented. Parvalbumin-containing neurons are mostly located within or in the vicinity of the granule or pyramidal cell layer. They form a subgroup of GABAergic neurons that has a target specificity for the cell body region. Their fine structural characteristics are identical to those known for hippocampal inhibitory neurons. Parvalbumin-containing neurons are involved in several inhibitory pathways: feed-back inhibition, feed-forward inhibition and disinhibition. The functional implications of our own as well as published data are discussed. Special consideration is given to the possible physiological role of parvalbumin in these neurons.
Animals↗
Entorhinal fibers form synaptic contacts on parvalbumin-immunoreactive neurons in the rat fascia dentata.
The entorhinal cortex gives rise to a dense projection to the outer two-thirds of the dentate molecular layer. The main target neurons are the granule cells. This study demonstrates that entorhinal fibers labeled by anterograde degeneration also terminate on parvalbumin-containing non-granule cells in the rat fascia dentata. Since the calcium-binding protein parvalbumin was recently found coexistent with gamma-aminobutyric acid in inhibitory hippocampal neurons, the described connection provides evidence for a role of entorhinal fibers in feed-forward inhibition of the granule cells.
Animals↗
Cryostat sections for coexistence studies and preembedding electron microscopic immunocytochemistry of central and peripheral nervous system tissue.
Perfusion-fixed tissue blocks were incubated in high molar sucrose solutions, shock frozen in melting isopentane, and sectioned on a conventional cryostat. Semithin sections (2-4 microns) alternatingly stained for parvalbumin and glutamate decarboxylase enabled us to demonstrate the coexistence of both antigens in the same cell. Thick sections (40 microns) of central and peripheral nervous system tissue were immunostained and processed for correlated light and electron microscopic studies. At the electron microscopic level, the preservation of ultrastructural features such as membranes and synaptic contacts was comparable to that normally seen in vibratome sectioned material. Hence, this technique can successfully be used for preembedding coexistence studies and electron microscopic preembedding immunocytochemistry when vibratome sectioning is problematic.
Animals↗
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↗
[The position of the supracondylar correction osteotomie during the treatment of the senile gonarthrosis (author's transl)].
The position of the supracondylar correction osteotomie during the treatment of the senile gonarthrosis is examined by controls of 17 patients with 21 performed osteotomies. The indication, the technique as well as the clinical and radiological results of the operation are critically dealt with. In case of a correct indication and when considering the contra-indication-like and existing strong osteoporosis, a distinct deficit of expansion and a most serious arthrosis-good results can be expected.
Aged↗