Insulin resistance, impaired glucose handling, hypercholesterolemia, hypertension and obesity contribute to the metabolic syndrome. Recently, there has been a growing interest in the ability of dietary polyphenols to reduce the adverse effects of these factors. Kudzu root extract has a long history of use in traditional Chinese medicine, and our previous studies demonstrate that kudzu root extract provides cardiovascular benefits and improves glycemic and lipid control in spontaneously hypertensive rats. The present study tested whether dietary kudzu root extract also improves glycemic control and hyperinsulinemia in ob/ob mice. Male ob/ob and control mice (2‐month‐old) were placed on a 0.2 % kudzu containing diet or a control diet that was otherwise polyphenol free. After 3 and 8 months on the diets, plasma glucose concentration was lower in kudzu‐treated vs. control mice. Oral glucose tolerance tests (2 g/kg bw) demonstrated that in ob/ob mice dietary kudzu root extract decreased peak elevations in blood glucose (179 [kudzu diet] vs. 273 mg/dl [control diet] increases at 45 minutes). Plasma insulin concentration was lower in kudzu treated compared to control mice. The results indicate that dietary kudzu root extract improves glucose handling in ob/ob mice and suggest that kudzu polyphenols improve insulin resistance in this model.
Transgenic AD model mice overexpressing APPswe develop plaques (with a thioflavine S positive core) and diffuse deposits. We have shown that these amyloid β deposits have a specific time course of development with plaques appearing before diffuse deposits. We hypothesized that local overexpression of APP would cause APP overproduction leading to Aβ pathology, i.e., the mice would show locally increased amyloid deposition. Young adult, C57BL/6 animals were injected in the entorhinal cortex with an adeno–associated virus (AAV) that expresses human APP (with the swedish mutation), and sacrificed 1 and 3 months later. The animals were transcardially perfused, the brains were cut and stained for APP, Aβ and inflammatory markers. In the animals with 1 month of survival following the injection there is a high number of cells expression APP at the injection site, and APP and a few amyloid deposits are present. Mice with 3 months survival demonstrated significantly increased numbers of amyloid deposits, further, some diffuse deposits were present. These results support the hypothesis that amyloid deposits can originate from local brain APP metabolism, independent of (over)expression of mutant or normal protein. Focal expression of mutant APP may overwhelm catabolic or transport mechanisms that normally dispose of amyloidogenic APP fragments.
Untreated essential hypertension leads to cardiovascular and renal disease and stroke, but antihypertensive drug therapy effectively reduces these consequences of hypertension. Several studies indicate that hypertension can negatively impact on cognitive function, especially on learning and memory, but the ability of antihypertensive drugs to ameliorate these cognitive dysfunctions is less clear. None of the recent studies convincingly demonstrates that any of the antihypertensive drugs currently in use has a major deleterious effect on cognition in hypertensive patients, but some of the drugs more reliably benefit cognitive function in the hypertensive patient. As a class, the angiotensin-converting enzyme inhibitors most consistently lead to cognitive improvement in the overall hypertensive population, but pradrenergic receptor blockers and a subset of calcium channel blockers appear to have very similar effects. Animal studies and clinical studies in demented patients suggest that angiotensin-converting enzyme in the cerebral cortex plays a role in normal learning and memory, a finding that provides a theoretic foundation to the beneficial actions of this class of drugs on cognitive function in hypertensive individuals.
Abstract The morphology and connections of the indusium griseum (IG) and anterior hippocampal continuation (AHC) suggest that this cortex contains analogues to several portions of the hippocampal formation. Whereas the outer neuronal layer of this cortex is made up of cells which are similar in structure to the neurons of the granule cell layer of the dentate gyrus, the three successively deeper layers contain morphological analogues to the neurons of the dentate hilus, Ammon's horn, and the subiculum, respectively. The neurons within each of these four layers of the AHC and IG have afferent and efferent connections which are quite similar to the connections of their hippocampal counterparts. Thus, the granule cells of the IG and AHC receive laminar inputs from the entorhinal cortex, the IG‐AHC itself, and the supramammillary region. Each of these three classes of inputs ends at successively more proximal positions on the dendritic tree of these granule cells. Other inputs to this region include those from the septal nuclei and the olfactory bulb. The deeper layers of the IG and AHC receive several inputs, including those from the thalamic and septal nuclei and the entorhinal cortex. The efferent cell bodies of the IG and AHC are segregated in such a way that the granule cells appear to give rise to only short connections, while the hilar cells project to the granule cells, the intermediate pyramidal neurons project to other portions of the IG and AHC and to the olfactory bulb, and the deep pyramidal neurons project to the diencephalon. These results demonstrate that the IG‐AHC is a continuation of the hippocampal formation.
Summary: Our previous studies demonstrate that chronic insulin administration exacerbates hypertension in spontaneously hypertensive rats (SHR). In the present study, we tested the hypothesis that the pressor effect of insulin in SHR is medicated by sympathetic nervous system overactivity. Male SHR (7 weeks old) were given daily subcutaneous injection of insulin or vehicle for 3 days, after which each rat received an intravenous infusion of the peripheral ganglionic blocker hexamethonium. Two days later, in a second experiment, the infusion protocol was repeated with the α2-adrenoceptor agonist clonidine, which more selectively inhibits sympathetic (as compared with parasympathetic) nervous system activity. Insulin treatment for 3 days caused a significant increase in mean arterial pressure (MAP; 164 ± 2 mm Hg vs. saline control 148 ± 3 mm Hg), but ganglionic blockade with hexamethonium eliminated the difference in blood pressure (BP) between the insulin-treated and control SHR. Infusion of clonidine significantly reduced MAP in the insulin-treated group to the level of the untreated control SHR, but the infusion did not reduce MAP in the latter group. In a second group of rats, acute administration of prazosin also eliminated the difference in MAP between insulin-treated and control SHR. We conclude that in SHR the sympathetic nervous system contributes importantly to the pressor effect of insulin administration and that this effect may be mediated by the central nervous system.
