The metabolic and neuroinflammatory changes induced by consuming a cafeteria diet are age-dependent.

OBJECTIVES: To compare the effects of a palatable cafeteria diet on serum parameters and neuroinflammatory markers of young and aged female Wistar rats. METHODS: Three-month-old (young) and 18-month-old (aged) female Wistar rats had access to a cafeteria diet (Caf-Young, Caf-Aged) or a standard chow diet (Std-Young, Std-Aged). RESULTS: The Caf-Young group showed a higher food consumption, weight gain, visceral fat depot, serum insulin and leptin levels, and the insulin resistance index (HOMA-IR) than the Std-Young group. The Caf-Aged group exhibited an increase in interleukin-1 levels in the cerebral cortex and hippocampus. The number of GFAP-positive cells did not differ between the groups, but there was a diet effect in the cerebral cortex and an age effect in the hippocampus. Phospho-tau expression did not differ between the groups. DISCUSSION: The 3- and 18-month-old rats responded differently to a cafeteria diet. Insulin and leptin levels are elevated in young animals fed a cafeteria diet, whereas aged animals are prone to neuroinflammation (indicated by an increase in interleukin-1ß levels). A combination of hypercaloric diet and senescence have detrimental effects on the inflammatory response in the brain, which may predispose to neurological diseases.

Female rats are more susceptible to metabolic effects of dehydroepiandrosterone treatment.

Dehydroepiandrosterone (DHEA) is a steroid hormone that presents several effects on metabolism; however, most of the studies have been performed on male animals, while few authors have investigated possible sex differences regarding the metabolic effects of DHEA. Therefore, the aim of this study was to evaluate the effect of different doses of DHEA on metabolic parameters of male and ovariectomized female Wistar rats. Sex differences were found in the metabolism of distinct substrates and in relation to the effect of DHEA. In respect to the glucose metabolism in the liver, the conversion of glucose to CO2 and the synthesis of lipids from glucose were 53% and 33% higher, respectively, in males. Also, DHEA decreased hepatic lipogenesis only in females. Regarding the hepatic glycogen synthesis pathway, females presented 73% higher synthesis than males, and the effect of DHEA was observed only in females, where it decreased this parameter. In the adipose tissue, glucose uptake was 208% higher in females and DHEA decreased this parameter. In the muscle, glucose uptake was 168% higher in females and no DHEA effect was observed. In summary, males and females present a different metabolic profile, with females being more susceptible to the metabolic effects of DHEA.

Effects of progesterone on the neonatal brain following hypoxia-ischemia.

Progesterone displays a strong potential for the treatment of neonatal hypoxic-ischemic encephalopathy since it has been shown to be beneficial in the treatment of the central nervous system injuries in adult animals. Here, we evaluated the effects of the administration of progesterone (10 mg/kg) in seven-days-old male Wistar rats submitted to neonatal hypoxia-ischemia (HI). Progesterone was administered immediately before ischemia and/or 6 and 24 h after the onset of hypoxia. The body weight of the animals, the volume of brain lesion and the expression of p-Akt and procaspase-3 in the hippocampus were evaluated. All animals submitted to HI showed a reduction in the body weight. However, this reduction was more remarkable in those animals which received progesterone before surgery. Administration of progesterone was unable to reduce the volume of brain damage caused by HI. Moreover, no significant differences were observed in the expression of p-Akt and procaspase-3 in animals submitted to HI and treated with either progesterone or vehicle. In summary, progesterone did not show a neuroprotective effect on the volume of brain lesion in neonatal rats submitted to hypoxia-ischemia. Furthermore, progesterone was unable to modulate p-Akt and procaspase-3 signaling pathways, which may explain the absence of neuroprotection. On the other hand, it seems that administration of progesterone before ischemia exerts some systemic effect, leading to a remarkable reduction in the body weight.

Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS.

DHEA is a neuroactive steroid, due to its modulatory actions on the central nervous system (CNS). DHEA is able to regulate neurogenesis, neurotransmitter receptors and neuronal excitability, function, survival and metabolism. The levels of DHEA decrease gradually with advancing age, and this decline has been associated with age related neuronal dysfunction and degeneration, suggesting a neuroprotective effect of endogenous DHEA. There are significant sex differences in the pathophysiology, epidemiology and clinical manifestations of many neurological diseases. The aim of this study was to determine whether DHEA can alter glucose metabolism in different structures of the CNS from male and female rats, and if this effect is sex-specific. The results showed that DHEA decreased glucose uptake in some structures (cerebral cortex and olfactory bulb) in males, but did not affect glucose uptake in females. When compared, glucose uptake in males was higher than females. DHEA enhanced the glucose oxidation in both males (cerebral cortex, olfactory bulb, hippocampus and hypothalamus) and females (cerebral cortex and olfactory bulb), in a sex-dependent manner. In males, DHEA did not affect synthesis of glycogen, however, glycogen content was increased in the cerebral cortex and olfactory bulb. DHEA modulates glucose metabolism in a tissue-, dose- and sex-dependent manner to increase glucose oxidation, which could explain the previously described neuroprotective role of this hormone in some neurodegenerative diseases.

DHEA administration modulates stress-induced analgesia in rats.

An important aspect of adaptive stress response is the pain response suppression that occurs during or following stress exposure, which is often referred to as acute stress-induced analgesia. Dehydroepiandrosterone (DHEA) participates in the modulation of adaptive stress response, changing the HPA axis activity. The effect of DHEA on the HPA axis activity is dependent on the state and uses the same systems that participate in the regulation of acute stress-induced analgesia. The impact of DHEA on nociception has been studied; however, the effect of DHEA on stress-induced analgesia is not known. Thus, the aim of the present study was to evaluate the effect of DHEA on stress-induced analgesia and determine the best time for hormone administration in relation to exposure to stressor stimulus. The animals were stressed by restraint for 1h in a single exposure and received treatment with DHEA by a single injection before the stress or a single injection after the stress. Nociception was assessed with a tail-flick apparatus. Serum corticosterone levels were measured. DHEA administered before exposure to stress prolonged the acute stress-induced analgesia. This effect was not observed when the DHEA was administered after the stress. DHEA treatment in non-stressed rats did not alter the nociceptive threshold, suggesting that the DHEA effect on nociception is state-dependent. The injection of DHEA had the same effect as exposure to acute stress, with both increasing the levels of corticosterone. In conclusion, acute treatment with DHEA mimics the response to acute stress indexed by an increase in activity of the HPA axis. The treatment with DHEA before stress exposure may facilitate adaptive stress response, prolonging acute stress-induced analgesia, which may be a therapeutic strategy of interest to clinics.

Sex-related differences in the effects of high-fat diets on DHEA-treated rats.

Several studies have investigated the beneficial effects of dehydroepiandrosterone (DHEA) on lipid and glucose metabolism. However, many of these studies are inconclusive about the effects of DHEA administration on metabolic disorders, and there appear to be sex-related differences in the effects of DHEA treatment. Few animal studies have addressed the effects of DHEA on diet-induced metabolic disorders. The present study sought to ascertain whether sex differences exist in the effects of a high-fat diet (HFD) on weight gain, adiposity, and biochemical and hormonal parameters in DHEA-treated rats. Rats were fed a HFD for 4 weeks and simultaneously received treatment with DHEA (10 mg/kg by subcutaneous injection) once weekly. Body weight, retroperitoneal fat depot weight, serum glucose, insulin, and leptin levels, and hepatic lipids were measured. HFD exposure increased the adiposity index in both sexes, the hepatic triglyceride content in both sexes, and the hepatic total cholesterol level in males. Moreover, the HFD induced an increase in blood glucose levels in both sexes, and hyperinsulinemia in males. In this experimental model, DHEA treatment reduced hepatic triglyceride levels only in females, regardless of HFD exposure. Exposure to a HFD, even if it does not cause obesity, may enhance risk factors for metabolic disorders, and males are more sensitive to this effect. DHEA treatment can help prevent metabolic derangements, but its effect varies with sex.

Effect of acute stress on sexual behavior in female rats: participation of the central angiotensinergic system.

Stress might influence the reproductive behavior in females, and central angiotensin II (Ang II) is a peptide that plays a role in stress response and in the modulation of sexual behavior. The medial amygdala (MeA), an important structure that regulates this behavior, is strongly involved in stress response. The aim of the present study was to evaluate the effect of acute restraint stress on the night of proestrus on sexual receptivity in female rats and the participation of Ang II and MeA in this effect. Adult female Wistar rats with regular estrous cycles were utilized. The acute stress protocol utilized was the restraint stress for 15 min on the night of proestrus. The participation of Ang II was evaluated by injecting Ang II and Ang II receptor antagonists (losartan and PD12319) into the MeA. The lordosis quotient was recorded. The stress or the microinjection of Ang II into the MeA significantly reduced sexual behavior. The blockade of AT(1) or AT(2) receptors in the MeA prevented the effect of stress and the effect of Ang II microinjection into this nucleus on sexual receptivity. We concluded that acute restraint stress on the night of proestrus reduces sexual behavior in rats, and this effect is mediated by both AT(1) and AT(2) receptors in the MeA.