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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 777 (1996), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Notes: Interactions between abnormal amyloid precursor protein metabolism and cholinergic dysfunction are increasingly apparent. Both of these major features of Alzheimer's disease occur in restricted loci in normal aging–a potential model for early Alzheimer type pathology. Entorhinal cortex is particularly vulnerable to β-amyloidosis and compared with other cortical areas is remarkable for the relatively high density of nicotinic (3H-nicotine) but not other cholinergic or glutamate receptor binding. With increasing age, post-maturity, there is a persistent decline in nicotinic receptor binding in entorhinal cortex whereas muscarinic Ml and non-Ml, glutamate NMDA and non-NMDA receptors are spared. Normal elderly individuals, distinguished by the absence of βA4 immunoreactive plaques in this area, are differentiated from those with plaques by higher nicotine binding. Amongst individuals with an established history of smoking tobacco, nicotinic receptor binding and hippocampal choline acetyltransferase were elevated compared with non-smokers and preliminary evidence indicates a reduced density of cortical plaques. These findings are consistent with the hypothesis that down regulation of the nicotinic cholinergic receptor—a ligand gated calcium channel known to control the expression of neurotrophins—plays a role in the evolution of Alzheimer-type pathology.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The Wobbler mouse (wr) is a mutant that exhibits loss of anterior horn ceils in the spinal cord and brainstem and subsequent muscle wasting, particularly of the fore-limbs and neck. The wr mice, 2–3 months of age, were found to have increased levels of immunoreactive-thyrotrophin-releasing hormone (ir-TRH) in the spinal cord and pons and medulla, but not in other CNS areas. This increase was observed in dorsal and ventral cord and at cervical, thoracic, and lumbar levels and was confirmed by HPLC to be authentic TRH. The levels of immunoreactive-somatostatin,-neurotensin, and-substance P were not raised in the CNS of wr mice. The activities of two peptidases capable of degrading TRH, pyroglutamylaminopeptidase (PGAP, EC 3.4.11.8) and proline endopeptidase (PEP, EC 3.4.21.26), and the level of 5-hydroxyindoleacctic acid were also raised in the spinal cord of 2–3-month-old wr mice although the activities of alanine aminopeptidase and lactate dehydrogenase and the level of 5-hydroxytrypt-amine were not. Increased spinal cord levels of ir-TRH and PGAP and PEP activities were not observed in the 1-month-old wr mice. In addition, a pilot study using spinal cord obtained at autopsy from three patients with motor neurone disease and 12 control subjects indicated no increase in spinal cord ir-TRH, PGAP, or PEP in human motor neurone disease.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 35 (1980), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The free amino acid content of the hippocampus, obtained at postmortem, has been analysed in cases of Alzheimer's disease and compared with normal cases. There were no significant differences in the levels of 23 amino acids including the transmitter candidates γ-aminobutyric, glutamic or aspartic acids. This finding is interpreted in relation to present knowledge of transmitter pathways in the region of the hippocampus. A tendency for some amino acids to be increased in the Alzheimer group reached statistical significance for arginine. This observation is consistent with increased proteolytic or peptidase activity in Alzheimer's disease.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 58 (1992), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: [3H]MK-801 binding was used as an index of the glutamate receptor W-methyl-D-aspartate-subtype channel to examine the influence of gender, age, mode of death (agonal status), interval between death and autopsy (postmortem delay), and time in storage at -70°C in well washed homogenate preparations from postmortem human frontal cortex. Basal binding and the modulatory effects of glutamate, glycine, spermidine, and zinc were examined with respect to these variables. Basal binding was sensitive to agonal status, being higher in sudden death cases. The effect of added glutamate and glycine was sensitive to age, with a trend toward lower binding with increasing age. The effect of added spermidine alone was sensitive to storage time at -70°C, the binding being higher with longer storage time. The effect of added zinc was also sensitive to postmortem delay, with zinc causing a greater reduction in binding with shorter postmortem delays. Thus, with the exception of gender, all variables examined influenced [3H]MK-801 binding, highlighting the attention that should be given to these factors in postmortem studies in normal and diseased human subjects.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract : Neuronal nicotinic acetylcholine receptors labelled with tritiated agonists are reduced in the cerebral cortex in Alzheimer's disease (AD), but to date it has not been demonstrated which nicotinic receptor subunits contribute to this deficit. In the present study, autopsy tissue from the temporal cortex of 14 AD cases and 15 age-matched control subjects was compared using immunoblotting with antibodies against recombinant peptides specific for α3, α4, and α7 subunits, in conjunction with [3H]epibatidine binding. Antibodies to α3, α4, and α7 produced one major band on western blots at 59, 51, and 57 kDa, respectively. [3H]Epibatidine binding and α4-like immunoreactivity (using antibodies against the extracellular domain and cytoplasmic loop of the α4 subunit) were reduced in AD cases compared with control subjects (p 〈0.02) and with a subgroup of control subjects (n = 9) who did not smoke prior to death (p 〈0.05) for the former two parameters. [3H]Epibatidine binding and cytoplasmic α4-like immunoreactivity were significantly elevated in a subgroup of control subjects (n = 4) known to have smoked prior to death (p 〈0.05). There were no significant changes in α3- or α7-like immunoreactivity associated with AD or tobacco use. The selective involvement of α4 has implications for understanding the role of nicotinic receptors in AD and potential therapeutic targets.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 29 (1977), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It is now widely recognized that histamine acts as a neurotransmitter in the mammalian central nervous system. Three selective histamine receptors have been described, all of which are present in the basal ganglia. This study is a detailed, quantitative, autoradiographical examination of the densities of histamine H3-receptors in coronal sections of human basal ganglia, using the selective ligand [3H]-(R)-α-methylhistamine. [3H]-(R)-α-methylhistamine binding was highest within the external and internal segments of the globus pallidus together with the substantia nigra. High levels were also found in the striatum, where density was significantly higher (P 〈 0.05) at a pre-, as opposed to post-, anterior commissure coronal level. Within the striatum, binding was noticeably higher in both the nucleus accumbens and acetylcholinesterase-deficient striosomes, while being undetectable in the subthalamic nucleus and very low in both the ventroanterior and ventrolateral thalamic nuclei. An intermediate level of binding, often with a laminar distribution, was seen in the insular cortex. [3H]-(R)-α-methylhistamine binding was also examined in both Parkinson's disease and Huntington's disease. No difference from control receptor density was found in any area examined in Parkinson's disease, while values were significantly lower in caudate (P 〈 0.001), putamen (P 〈 0.001), external (P 〈 0.001) and internal (P 〈 0.05) globus pallidus, although not the insular cortex, in Huntington's disease cases. These data suggest that H3-receptors are present upon striatonigral projection neurons of the direct and indirect movement pathways thus providing histaminergic control over the activity of both these circuits.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Anaesthesia 60 (2005), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 487 (1986), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 2 (1990), S. 149-158 
    ISSN: 1435-1463
    Keywords: Nicotinic receptor ; muscarinic receptor ; Alzheimer's disease ; Parkinson's disease ; senile dementia of Lewy body type
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cholinergic nicotinic and muscarinic receptor binding were measured in post mortem human brain tissue, using low (nM) concentrations of (3H)-nicotine to detect predominately the high affinity nicotinic site and (3H)-N-methylscopolamine in the presence and absence of 3×10−4 M carbachol to measure both the low and high affinity agonist subtypes of the muscarinic receptor group. Consistent with most previous reports, the nicotinic but not muscarinic binding was reduced in the different forms of dementia associated with cortical cholinergic deficits, including Alzheimer's and Parkinson's disease, senile dementia of Lewy body type (SDLT) and Down's syndrome (over 50 years). Analysis of (3H)-nicotine binding displaced by a range of carbachol concentrations (10−9–10−3 M) indicated 2 binding sites for nicotine and that the high affinity rather than low affinity site was reduced in Alzheimer's disease. In all 3 cortical areas investigated (temporal, parietal and occipital) there were increases in the low affinity muscarinic site in Parkinson's disease and SDLT but not Alzheimer's disease or middle-aged Down's syndrome. This observation raised the question of whether the presence of neurofibrilalry tangles (evident in the latter but not former 2 disorders) is incompatible with denervation-induced muscarinic supersensitivity in cholinoceptive neurons which include cortical pyramids generally affeced by tangle formation.
    Type of Medium: Electronic Resource
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