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51.
A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. 总被引:36,自引:0,他引:36
S Weggen J L Eriksen P Das S A Sagi R Wang C U Pietrzik K A Findlay T E Smith M P Murphy T Bulter D E Kang N Marquez-Sterling T E Golde E H Koo 《Nature》2001,414(6860):212-216
Epidemiological studies have documented a reduced prevalence of Alzheimer's disease among users of nonsteroidal anti-inflammatory drugs (NSAIDs). It has been proposed that NSAIDs exert their beneficial effects in part by reducing neurotoxic inflammatory responses in the brain, although this mechanism has not been proved. Here we report that the NSAIDs ibuprofen, indomethacin and sulindac sulphide preferentially decrease the highly amyloidogenic Abeta42 peptide (the 42-residue isoform of the amyloid-beta peptide) produced from a variety of cultured cells by as much as 80%. This effect was not seen in all NSAIDs and seems not to be mediated by inhibition of cyclooxygenase (COX) activity, the principal pharmacological target of NSAIDs. Furthermore, short-term administration of ibuprofen to mice that produce mutant beta-amyloid precursor protein (APP) lowered their brain levels of Abeta42. In cultured cells, the decrease in Abeta42 secretion was accompanied by an increase in the Abeta(1-38) isoform, indicating that NSAIDs subtly alter gamma-secretase activity without significantly perturbing other APP processing pathways or Notch cleavage. Our findings suggest that NSAIDs directly affect amyloid pathology in the brain by reducing Abeta42 peptide levels independently of COX activity and that this Abeta42-lowering activity could be optimized to selectively target the pathogenic Abeta42 species. 相似文献
52.
Viscero-somatic reflexes have been studied by recording monosynaptic reflexes following distension of the urinary bladder in intact, decerebrate and spinal animals. It was observed that the viscero-somatic responses following bladder distension are inhibitory in nature and this inhibition was highest in decerebrates and least in spinal animals. The site of viscero-somatic interaction probably lies in the bulbar area (supraspinal) and spinal cord. 相似文献
53.
Electron microscopic analysis of neocortical transplants in the cerebellum of the host animals showed that the nerve cells, glial cells, and neuropil of the transplants were normal. These transplants showed anatomical integration with the host brain through various regions of interface. Neuropil interfaces were found to have a high density of synaptic profiles, and medullary interfaces had a very small number of synaptic profiles. 相似文献
54.
Transplantation of neural tissues in the brains of laboratory mammals: technical details and comments. 总被引:1,自引:0,他引:1
Various technical details on the transplantation of the embryonic neural tissues in the brains of the neonatal and adult rats are presented. Conditions determining successful or leading to unsuccessful survival, growth and differentiation of these transplants are critically examined. 相似文献
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Summary The calcitonin cells of adult rhesus monkeyMacaca mulatta are located in the central region of thyroid along the median axis. The anterior and posterior poles, the isthmus and peripheral regions of thyroid are completely devoid of C cells. The parathyroid also lacks C cells. 相似文献
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