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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 65 (1984), S. 85-88 
    ISSN: 1432-0533
    Keywords: Nucleus basalis of Meynert ; Neuronal loss ; Creutzfeldt-Jakob disease ; Dementia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a man of 47 with a 2-month history of Creutzfeldt-Jakob-disease verified neuropathologically a morphometric study of the nucleus basalis of Meynert, the major source of cholinergic innervation of the cortex, revealed a neuronal loss of 45%. The degeneration of these neurones may provide the morphological substrate of the cortical cholinergic deficiency which has been reported in this condition. The six subpopulations of the nucleus basalis were affected in different degrees. Neuronal loss was most pronounced in those subpopulations which project to cortical areas most affected by spongiosis and neuronal loss. It is suggested that maintenance of the nucleus basalis complex is a necessary condition for higher cortical function.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Nucleus basalis of Meynert ; Amyloid ; Neuronal loss ; Alzheimer's disease ; Dementia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The deficiency of the cholinergic cortical projection system arising in the different basal forebrain structures collectively referred to as nucleus basalis of Meynert complex is a constant finding in Alzheimer's disease, a disorder which is neuropathologically characterised by the appearance of three intracerebral formes of twisted β-pleated sheet (amyloid) fibrils, neurofibrillary tangles, amyloid-containing neuritic plaques and congophilic amyloid angiopathy. In the present study the quantitative relationship between these hallmarks of the disease, amyloid deposition and neuronal loss in the cholinergic basal forebrain system, was investigated in ten cases of Alzheimer's disease. Besides a constant involvement of the cerebral cortex and hippocampus, all cases of Alzheimer's disease show a large amount of amyloid in the medial septal nucleus, in the diagonal band nucleus and in the substantia innominata which is correlated with neuronal loss in these areas. These amyloid deposits in the basal forebrain are due to congophilic angiopathy associated with plaques and neurofibrillary tangles. The distribution of amyloid deposition in the basal forebrain is restricted entirely to those neuronal clusters which represent the origin of cholinergic innervation of the cerebral cortex and hippocampus. Immediately adjacent structures are not affected. These findings suggest a pathogenetic role of amyloid deposition in the mechanism of degeneration of the cholingeric basal forebrain system.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Key words Aging ; Animal model ; Cortex ; Microtubule-associated protein tau ; Hyperphosphorylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aged individuals of mammalian species displaying hyperphosphorylated tau protein may be suitable natural models for investigating neurodegenerative alterations occurring, for example, in Alzheimer’s disease. Therefore, autoptic tissue from the entorhinal, motor and prefrontal cortices of 14 mammalian species was screened using the monoclonal antibody AT8, which is directed against a phosphorylated epitope of human tau and applicable to the tissues of aged domestic animals, as shown in previous studies. AT8-immunoreactive neuronal processes and perikarya were revealed in Campbell’s guenon, rhesus monkey, baboon, rabbit, spectacled bear, guanaco, reindeer and bison. Signs for considerable neuropathological alterations in aged bisons also included neuropil threads, whereas AT8 immunoreactivity in the other species was only sparsely scattered. Hyperphosphorylated tau in the brain of an 28-year-old rhesus monkey was also detected by AT100, PHF-1 and TG-3 antibodies, but only in the hippocampal formation and entorhinal cortex, which are known as starting point for tangle spreading in the cortex of Alzheimer patients.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: Nucleus basalis of Meynert ; Neuronal loss ; Dementia ; Alzheimer's disease ; Paralysis agitans ; Korsakoff's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The nucleus basalis of Meynert, the major source of cholinergic innervation of the cerebral cortex, was morphometrically investigated in 58 cases of neuropsychiatric disorders and compated to 14 controls. The results demonstrate a loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease (70%), paralysis agitans (77%), and Korsakoff's disease (47%) but no marked reduction of neurons in postencephalitic parkinsonism, Huntington's disease, chronic alcoholism without dementia, schizophrenia and infantile brain damage. Neurons of the three subdivisions of the nucleus basalis of Meynert (the nucleus septi medialis, the nucleus of the diagonal band of Broca and the nucleus basalis Meynert neurons in the substantia innominata) may be affected in a different manner in different patients within a single group homogeneous with respect to the usual clinical and neuropathological diagnostic criteria. Cell loss in the basal forebrain is restricted to the large neurons of the nucleus basalis, the immediately adjacent neurons of the globus pallidus externus not being affected. The selective degeneration of these neurons provides the morphological correlate of the cortical cholinergic deficiency in these neuropathological conditions. The degeneration of this discrete cholinergic neuronal population in several disorders of higher cortical function is probably directly related to the progressive deterioration of memory and cognitive processes in affected patients.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1238
    Keywords: Key words Cytokines ; Euthyroid sick syndrome ; Non-thyroidal illness ; Hypothalamo-pituitary-adrenal axis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine whether cytokine release or activation of the hypothalamo-pituitary-adrenal (HPA) axis is predominantly involved in the development of the euthyroid sick syndrome (ESS). Design: Prospective observational study. Setting: Intensive care unit at a tertiary care medical center in Germany. Patients: Nine patients with sepsis of different causes and eight patients with acute myocardial infarction. Interventions: None. Measurements and results: Immediately on admission and on day 7 the following parameters were determined: total thyroxine (T4), free thyroxine (FT4), total triiodothyronine (T3), thyrotropin (TSH), interleukin-1β (IL-1β), interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), serum cortisol and plasma adrenocorticotropin (ACTH). On admission, concentrations of all thyroid hormones and TSH were significantly lower in septic patients compared to non-septic patients, whereas all cytokines except IL-2 were significantly elevated in the sepsis group. By contrast, there was no difference in serum cortisol and plasma ACTH levels between the two groups. On day 7, T4 and T3 were still lower in the septic group, whereas IL-1β, sIL-2R and IL-6 were still elevated. Again, no differences were found with regard to cortisol and ACTH levels. Conclusions: Euthyroid sick syndrome occurs very early during the course of septic diseases. Significantly decreased levels of total T4, FT4, T3 and TSH in septic patients suggest central suppression of TSH as well as inhibition of thyroid hormone release in ESS. The HPA axis is activated in septic patients and in non-septic patients and does not contribute to the development of ESS.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: 3-Bromopyruvate inhibits pyruvate decarboxylase in brain homogenates and causes a 90% drop in acetylcholine tissue content at a concentration of 2 mM. Stereotaxic injection of 3-bromopyruvate into the basal forebrain causes after 7 days a 40% drop of acetylcholine concentration and pyruvate decarboxylase activity in the cortex and hippocampus, and greater decreases at the site of injection. However, values return to normal 18 days after injection. Choline ace-tyltransferase is partially inhibited only at the site of injection after 7 days. Choline transport and choline concentration are not affected at either 7 or 18 days after injection. Impairments in spontaneous alternation and in retention of passive avoidance were seen only 7 days after the injection. The results suggest that stereotaxic injection of bromopyruvate can induce discrete reversible cholinergic lesions on a time scale useful for behavioural experiments and for comparison with neurodegeneration.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 88 (2004), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Filamentous tau protein deposits are a pathological hallmark of a group of neurodegenerative disorders (tauopathies). Tau protein in these aggregates is highly phosphorylated at different phosphorylation sites. Although tau filaments can be formed by heparin-induced aggregation of unphosphorylated recombinant tau, it is not known how tau phosphorylation modulates aggregation behaviour. Analysis of the effect of tau phosphorylation at defined single or multiple sites is hampered by the low specificity of protein kinases and the highly dynamic turnover of phosphorylation in vivo. To overcome this problem we employed site-directed mutagenesis to convert serine and threonine to aspartic acid or glutamic acid, which introduce a negative charge and conformational change that mimic phosphorylation. We tested 14 different mutated tau proteins for their propensity for self-aggregation and formation of tau filaments. Tau aggregation was monitored with thioflavin S fluorescence in the presence of different inducers such as heparin, Al3+, Fe2+ and Fe3+. We found that mutations in the N-terminal portion up to amino acid 208 mainly suppress tau aggregation, whereas mutations in the C-terminal region mainly lead to an enhanced aggregation. Mutations in the middle portion of tau showed a mixed picture of suppression and enhancement of aggregation. A single amino acid change Ser422Glu has aggregation-favouring properties with all four inducers.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 107 (2000), S. 451-461 
    ISSN: 1435-1463
    Keywords: Keywords: Primary guinea pig neurons, okadaic acid, metabolic labelling, amyloid precursor protein, Aβ peptide, Alzheimer's disease, DNA fragmentation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Primary cultures of guinea pig neurons were used as a model system to study the influence of the protein phosphatase inhibitor okadaic acid (OA) on the secretion, processing and phosphorylation of the amyloid precursor protein (APP). This primary cell culture system mimics more closely than other cell culture systems the human in vivo condition, as guinea pig APP is 98% homologous to human APP at the protein level, identical regarding the Aβ sequence and is processed in a similar manner as human APP. Both intracellular and secreted APP was upregulated by OA treatment (0.3 nM–10 nM) of 14 days old cultures in a concentration dependent manner while the amount of Aβ in the medium was decreased. OA treatment did not affect cell membrane integrity of primary neurons but induced DNA fragmentation. Phosphorylation of APP was unchanged by the low OA concentration used. These results show that OA treatment of guinea pig primary cultures might be used as a model to study the effects of modulation of signal transduction on secretion and processing of APP.
    Type of Medium: Electronic Resource
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