Advanced glycation end products (AGEs) have been implicated in the chronic complications of diabetes mellitus and have been reported to play an important role in the pathogenesis of Alzheimer's disease. In this study, we examined the immunohistochemical localization of AGEs, amyloid beta protein (A beta), apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer's disease and other neurodegenerative diseases (progressive supranuclear palsy, Pick's disease, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In most senile plaques (including diffuse plaques) and CAA from Alzheimer's brains, AGE and ApoE were observed together. However, approximately 5% of plaques were AGE positive but A beta negative, and the vessels without CAA often showed AGE immunoreactivity. In Alzheimer's disease, AGEs were mainly present in intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs. Pick's bodies in Pick's disease and granulovacuolar degeneration in various neurodegenerative diseases were also AGE positive. In non-Alzheimer neurodegenerative diseases, senile plaques and NFTs showed similar findings to those in Alzheimer's disease. These results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative diseases, including Alzheimer's disease.
To determine the effects of manual acupuncture stimulation (MAS) on skin sympathetic nerve activity (SSNA), SSNA and skin blood flow (SBF) were measured during a resting period and during MAS. Twelve healthy male subjects were divided into an acupuncture group (n = 7) and a control group (n = 5). SSNA was recorded from the left median nerve at the elbow using microneurography, while SBF was recorded using laser Doppler flowmeter. In the acupuncture group, MAS was delivered to LI 4 point in the right thenar muscle. The acupuncture needle was retained for 2 minutes before being removed. SSNA and SBF recordings were performed for a total of 12 minutes, from 5 minutes prior to MAS until the end of the trial. In the control group, the 2-minute period of acupuncture was replaced by 2 minutes of rest. During the first minute of MAS, we observed an increase in SSNA accompanied by a reduction in SBF. In the acupuncture group, these parameters returned to baseline values in the second minute of MAS. Parameters in the control group were unchanged throughout the experimental procedure. A significant negative correlation was observed between changes in SSNA and SBF during the first minute of MAS. In addition, a negative correlation was demonstrated between the basal value of SSNA and the change in SSNA in response to MAS. These results suggest that MAS elicited a transient increase in SSNA and that this increase is dependent on the baseline of SSNA.
Kuru, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler syndrome (GSS) are transmissible dementias affecting humans characterized neuropathologically by intraneuronal vacuolation, spongiform change, astrocytic hypertrophy and hyperplasia and the variable presence of amyloid plaques. It has been suggested that microglia are amyloid-forming cells, which play an essential role in amyloid plaque formation. To study the relationship between microglia and amyloid plaques in kuru, CJD and GSS, cerebellar tissues were examined by the double-immunostaining technique using anti-ferritin antibodies as the microglial marker and anti-scrapie amyloid antibody as plaque marker. Ferritin-immunoreactive microglia were observed interdigitating with and among unicentric, multicentric and diffuse types of scrapie amyloid-immunoreactive plaques and were found to a lesser extent in the neuropil. In kuru and CJD, scrapie amyloid-immunoreactive plaques were predominantly unicentric and were observed in the granular layer. In kuru, 53% of the amyloid plaques were associated with microglia, whereas only 30% of plaques in CJD were. In contrast, scrapie-amyloid-immunoreactive plaques in GSS were of the multicentric type, predominantly observed in the molecular layer, and 90% of these plaques were associated with microglia. Our data indicate that microglia are frequently associated with scrapie amyloid-immunoreactive plaques in GSS, less commonly in kuru and to a much lesser extent in CJD, suggesting that microglia may play a variable but important role in the formation of plaques in the transmissible spongiform encephalopathies.
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