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Background: Converging evidence indicates prolactin (PRL) and diabetes play an important role in the pathophysiology of cognitive impairment. However, little is known about the mechanisms responsible for the effects of PRL and diabetes on cognitive impairment. Summary: We summarize and review the available literature and current knowledge of the association between PRL and diabetes on aspects of cognitive impairment. Key Messages: The phosphatidylinositol 3-kinase/protein kinase B pathway is central to the molecular mechanisms underlying how PRL and diabetes interact in cognitive impairment. Further work is needed to identify the interaction between PRL and diabetes, especially in the molecular aspects of cognitive impairment, which can suggest novel strategies for cognitive dysfunction treatment. [ABSTRACT FROM AUTHOR]

Using proteomic techniques, we investigated peroxynitrite (ONO[O.sup.-]) and 4-hydroxy-2-nonenal (HNE) modified serum proteins from young and old Fischer 344 rats. Two-dimensional gel electrophoresis/western blot analysis of nitrotyrosine and HNE-histidine revealed that serum proteins were differentially modified by ONO[O.sup.-] and HNE. Among them, 16 of the modified proteins, identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), are involved in blood coagulation, lipid transport, blood pressure regulation, and protease inhibition. Furthermore, nitration and HNE adduction were found to increase with age, lending support to the oxidative stress hypothesis of aging. Our data showed that proteomic techniques can be valuable tools in the study of protein profiling modifications during aging.

To investigate effects of aging on adhesion molecules (AMs), the present study assessed the expressions of aortic P-selectin and vascular adhesion molecule-1 (VCAM-1) in young (6-monthold) and old (24-month-old) Fischer 344 rats fed ad libitum (AL) or calorie-restricted diets. Results showed increased levels of aortic P-selectin and VCAM-1 in the old AL rats, causing excessive leukocyte infiltration as indicated by enhanced myeloperoxidase level. These elevations were parallel to increased oxidative stress including lipid peroxides during aging. Then involvement of redox-sensitive transcription factor nuclear factor-[kappa]B was analyzed, and greater activation of nuclear factor-[kappa]B-inducing kinase (NIK)/I[kappa]B kinase (IKK)/Inhibitor of [kappa]B (I[kappa]B) pathway in aorta from old AL rats was found. Further, in cultured endothelial cells challenged by various oxidative stimuli, the induced redox imbalance triggered overexpression and promoter activities of P-selectin and VCAM-1. Our study documented that aortic upregulated AMs with age are closely related to activation of NIK/IKK/I[kappa]B/nuclear factor-[kappa]B pathway brought on by oxidative stress.

Betaine is an important human nutrient obtained from various foods. In the present study, we assessed the anti-inflammatory effect of betaine on nuclear factor-[kappa]B (NF-[kappa]B) during aging. Sprague-Dawley (SD) rats, ages 7 and 21 months, were used in this study. The older rats were fed betaine. To elucidate the effect of betaine on oxidative stress-induced NF-[kappa]B and its signaling pathway at molecular levels, YPEN-1 cells were used. Results showed that betaine suppressed NF-[kappa]B and its related gene expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), vascular cell adhesion molecule-1 (VCAM-1), and intracellular cell adhesion molecule-1 (ICAM-1) in aged kidney. Furthermore, betaine attenuated oxidative stress-induced NF-[kappa]B via nuclear factor-inducing kinase/I[kappa]B kinase (NIK/IKK) and mitogen-activated protein kinases (MAPKs) in the YPEN-1 cells. On the basis of these results, we concluded that betaine suppressed the age-related NF-[kappa]B activities associated with upregulated NIK/IKK and MAPKs that were induced by oxidative stress. Thus, betaine might be useful as a preventive agent against the activation of NF-[kappa]B induced during inflammation and aging.

Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptor superfamily of transcription factors, are key regulators in various pathophysiological processes related to energy metabolism including lipid, carbohydrate metabolism, and inflammation. At present, little information is on the effect of age and calorie restriction (CR) on PPARs. In the present study, we investigated how age and CR (60% of the ad libitum intake) modulate PPARs in kidneys obtained from Fischer 344 rats, ages 13 and 25 months. Results showed that nuclear protein, mRNA level, and DNA binding activity of PPARs decreased with age, while CR blunted the reduction. Our findings were verified in separate experiments in which rats were injected with lipopolysaccharide, with the result of increased susceptibility to inflammation. Based on these findings, we conclude that the altered expression of PPARs may be due to increased oxidative stress with age, and that CR prevents these decreases through its antioxidative action.

The relevance of prostanoids to inflammation, thrombosis, and cardiovascular diseases is well known. The present study attempts to explore age effects on prostanoids and their biosynthesis cascade. Results from comparing prostanoid levels between young (6 months) and old (24 months) Fischer 344 rats showed rises of prostaglandin E2 (PG[E.sub.2]), PG[I.sub.2], and thromboxane [A.sub.2] (TX[A.sub.2]) levels in the old rats. Correlating evidence showed gene expression up-regulation of several prostanoid synthase enzymes in old rat aorta. Further, we found that expression of the antioxidant enzyme glutathione peroxidase was raised by age in the aorta, while superoxide dismutase and catalase expression showed no significant change during aging in the aorta. Moreover, calorie restriction (CR) was found to attenuate age-related prostanoid changes by suppressing inflammatory activities. In conclusion, the data from this study indicated that age-related increases in prostanoids and their biosynthesis might be closely associated with a weakened antioxidant capacity.