PPAR-α Expression Inversely Correlates with Inflammatory Cytokines IL-1β and TNF-α in Aging Rats

Abstract

Dehydroepiandrosterone (DHEAS) was given the name "fountain of youth" in reference to its beneficial properties in memory, cognition and aging. Cultured cell studies showed that DHEAS may mediate its action by counteracting aging-associated inflammation via PPAR-alpha activation. In the present study, we demonstrated an age-dependent increase in IL-1beta and TNF-alpha expression in the brain and the spleen of aging rats, while PPAR-alpha expression was decreased in the spleen of 18 month-old rats. Oral treatment with DHEAS increased PPAR-alpha mRNA in 3 month-old rats and decreased PPAR-alpha protein expression in 18 month-old rats in the spleen. In contrast, DHEAS did not alter cytokine expression in spleen and brain of the three age groups. These findings underline a differential role for DHEAS in PPAR-alpha expression that is age-dependent, and also, that beneficial effects of DHEAS on cognitive function are unlikely mediated by a decrease in cytokine expression.

The Multifaceted Profile of Activated Microglia

“…We have consistently reported that IL-1β concentration is increased in the hippocampus of aged rats where it is inversely related to the ability of rats to sustain LTP [173,199] and, although a correlation between these changes and expression of cell surface markers of microglial activation has been shown, these changes do not always occur simultaneously [204]. Like IL-1β, an increase in IL-6 has also been observed in brain tissue of aged, compared with young, animals [205] and a similar change in TNF-α has been reported in rats [206] and in aged senescenceaccelerated mice [207]. These findings, which are indicative of age-related neuroinflammation, are consistent with data obtained from microarray analysis of brain tissue prepared from young and aged animals in which an agerelated upregulation of genes involved in the immune response were documented [200,208].…”

Manganese Treatment Modulates the Expression of Peroxisome Proliferator-activated Receptors in Astrocytoma and Neuroblastoma Cells

“…Recent findings indicate that activation of PPARc attenuates b-amyloid-induced neurodegeneration [14]. A most recent study on rat brain and spleen suggests that PPARa mediates the effects of dehydroepiandrosterone, which has beneficial effects in memory, cognition and aging [39]. That study implicates a role of dehydroepiandrosterone in PPARa expression that is age-dependent.…”

“…The study on the spleen revealed PPARa expression decreased with age [39]. PPARc ligand (e.g., troglitazone) is known to induce growth inhibition in human brain tumor cell lines and this growth inhibition was found to be facilitated by PPARc-mediated induction of apoptosis [33,39]. Such findings suggest that treatment of glioma cells with PPARc agonists may have therapeutic potential for treatment of gliomas [33,40,41].…”

“…That study implicates a role of dehydroepiandrosterone in PPARa expression that is age-dependent. The study on the spleen revealed PPARa expression decreased with age [39]. PPARc ligand (e.g., troglitazone) is known to induce growth inhibition in human brain tumor cell lines and this growth inhibition was found to be facilitated by PPARc-mediated induction of apoptosis [33,39].…”

Advantages of nonhuman primates as preclinical models for evaluating stem cell-based therapies for Parkinson's disease

“…While rodents and humans share a great deal of similarity in the organization of the immune system (Haley, 2003;Bailey et al, 2013;Cho et al, 2015;Plackett et al, 2003;Gelinas and McLaurin, 2005;Ferrari et al, 2001), a growing body of literature suggests that immune systems of rodents and humans differ in ways that significantly hamper translation of results obtained in preclinical trials in rodents to successful therapeutics in humans (Renshaw et al, 2002;Boehmer et al, 2004;Rhoades and Orne, 1998;Swift et al, 2001;Rammos et al, 2014;Wang et al, 2014;Bruhns, 2012;Rousseaux et al, 1983;Mestas and Hughes, 2004). Rodents and humans respond differently to infectious agents and possess disparate inflammatory responses (Leist and Hartung, 2013;Tuomela and Lahesmaa, 2013).…”