Prolyl oligopeptidase (POP) have been suggested to participate in the pathogenesis of Alzheimer's disease (AD). In this study the activity of POP is evaluated in AD patients and in transgenic mice with substantial deposits of beta-amyloid (Abeta). In AD cases, the POP activity displayed a significant negative correlation with the scores of senile/neuritic plaques and neurofibrillary tangles but not with Abeta-load. The transgenic mice with high levels of Abeta did not have altered POP activity compared to wild type mice. Based on our results, the low POP activity in AD seems to be associated with neuronal degeneration rather than to Abeta accumulation.
The long-term effects of portacaval anastomosis (PCA) on histamine H3 receptors in rat brain were studied by in vitro and in vivo methods. The overflow of histamine from the anterior hypothalamus and from cortex after long-term PCA was determined by in vivo microdialysis. The binding properties of [3H]-R-alpha-methylhistamine in membranes from cortex, cerebellum, and rest of brain (ROB) were examined with saturation binding experiments. The regional distribution of [3H]-R-alpha-methylhistamine binding sites in the brain of sham- and PCA-operated rats was assessed also with autoradiography. The tissue levels of histamine were significantly elevated in cortex and ROB of PCA-operated rats. In addition, the spontaneous and K+-evoked overflow of histamine from anterior hypothalamus, and the thioperamide-induced overflow from both anterior hypothalamus and cortex were increased after chronic PCA. In spite of the significantly elevated tissue concentrations and the moderate increase in histamine release, the binding properties of [3HI-R-alpha-methylhistamine to cortical membranes were not significantly changed. However, the autoradiography study did reveal a decrease in [3H]-R-alpha-methylhistamine binding density, particularly in striatum and cortex, where H3 receptors are located mainly at non-histaminergic neurons. In conclusion, we suggest that there is a region-selective increase in the histaminergic activity in chronic PCA, which leads to the down-regulation of somadendritic and pre-synaptic H3 receptors located at non-histaminergic neurons. At the same time, the autoreceptor mediated control of histamine neuronal activity via pre-synaptic H3 receptors located at histaminergic neurons is preserved after long-term PCA.
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