Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5.

Hyperphosphorylation of microtubule-associated proteins such as tau and neurofilament may underlie the cytoskeletal abnormalities and neuronal death seen in several neurodegenerative diseases including Alzheimer's disease. One potential mechanism of microtubule-associated protein hyperphosphorylation is augmented activity of protein kinases known to associate with microtubules, such as cdk5 or GSK3beta. Here we show that tau and neurofilament are hyperphosphorylated in transgenic mice that overexpress human p25, an activator of cdk5.

Effects of cholestyramine and diet on small intestinal histomorphometry in rats.

Reports on the effects of cholestyramine on small intestinal structure of rats have produced contradictory data about changes in mucosal histomorphometry, perhaps due to interacting effects of dietary composition. In order to identify effects of cholestyramine and diet on structure of the small intestines, 40 male rats were divided into 4 groups of 10 and fed 1 of each of the following diets for 1 month: standard diet, purified fiber-free diet, standard diet + 2% cholestyramine, or purified fiber-free diet + 2% cholestyramine. Serum concentrations of cholesterol and triglycerides were moderately increased in rats fed the purified fiber-free diet versus the standard diet.

Changes in rat heart histomorphometry due to two-week dietary restriction.

In preclinical safety studies in which the administration of a test compound causes reductions in food consumption, body weights, and organ weights, it may be difficult to differentiate direct compound-induced effects on organ weights from those simply due to reduced nutrition. To address this problem in reference to the heart, hearts were obtained from rats that were known to have had reductions in body weights and absolute heart weights as a result of feed restriction. Rats (40/sex) were divided into 4 groups (10/sex) and given quantities of ad libitum diet for 2 wk as follows: Group 1, 100%; Group 2, 75%; Group 3, 50%; and Group 4, 25%.