Impact of glucocorticoid treatment before pregnancy on glucose homeostasis of offspring exposed to glucocorticoid in adult life.

AIMS: To explore the impact of GC administration periconceptionally on the glucose metabolism of adult offspring (male and female) and whether this periconception exposure might influence the metabolic outcomes when the offspring are also treated with dexamethasone in adult life. MATERIALS AND METHODS: Rats received a daily injection of dexamethasone (1 mg/kg, body mass) or saline solution (1 mL/kg body mass) for 7 consecutive days prior became pregnant. Male and female offspring had glucose homeostasis assessed at 3- and 6-month-old and after dexamethasone treatment (1 mg/kg, body mass) or vehicle for 5 consecutive days. Then, murinometric, functional, biochemical, and histomorphometric analyses were performed. KEY FINDINGS: Male and female offspring born from rats treated with GC prior to becoming pregnant had none of the murinometric and metabolic outcomes (i.e., body mass, food intake, blood glucose, plasma triacylglycerol, and glucose tolerance) changed up to 6-month-old. None of the expected diabetogenic effects caused by dexamethasone treatment at 6-month of age (i.e., elevation in fasting blood glucose, plasma insulin, triacylglycerol, and albumin, glucose intolerance, insulin insensitivity, augmentation in hepatic glycogen content, and increase in pancreatic islet mass) was observed in offspring born from rats treated with dexamethasone in the prepregnancy period. However, periconceptional exposure to GC predisposed the offspring of both sexes to a higher prevalence of augmented fed blood glucose values. SIGNIFICANCE: These results give validity for the use of GC as anti-inflammatory purposes in this critical periconceptional period, but highlight the importance to consider all parental habits when interpreting adult outcomes.

Glucose Homeostasis Is Not Affected in a Murine Model of Parkinson's Disease Induced by 6-OHDA.

There is a mutual relationship between metabolic and neurodegenerative diseases. However, the causal relationship in this crosstalk is unclear and whether Parkinson's disease (PD) causes a posterior impact on metabolism remains unknown. Considering that, this study aimed to evaluate the appearance of possible changes in metabolic homeostasis due to 6-hydroxydopamine (6-OHDA) administration, a neurotoxin that damage dopaminergic neurons leading to motor impairments that resemble the ones observed in PD. For this, male Wistar rats received bilateral 6-OHDA administration in the dorsolateral striatum, and the motor and metabolic outcomes were assessed at 7, 21, or 35 days post-surgical procedure. Dexamethasone, a diabetogenic glucocorticoid (GC), was intraperitoneally administered in the last 6 days to challenge the metabolism and reveal possible metabolic vulnerabilities caused by 6-OHDA. Controls received only vehicles. The 6-OHDA-treated rats displayed a significant decrease in locomotor activity, exploratory behavior, and motor coordination 7 and 35 days after neurotoxin administration. These motor impairments paralleled with no significant alteration in body mass, food intake, glucose tolerance, insulin sensitivity, and biochemical parameters (plasma insulin, triacylglycerol, and total cholesterol levels) until the end of the experimental protocol on days 35-38 post-6-OHDA administration. Moreover, hepatic glycogen and fat content, as well as the endocrine pancreas mass, were not altered in rats treated with 6-OHDA at the day of euthanasia (38th day after neurotoxin administration). None of the diabetogenic effects caused by dexamethasone were exacerbated in rats previously treated with 6-OHDA. Thus, we conclude that bilateral 6-OHDA administration in the striatum causes motor deficits in rats with no impact on glucose and lipid homeostasis and does not exacerbate the adverse effects caused by excess GC. These observations indicate that neurodegeneration of dopaminergic circuits in the 6-OHDA rats does not affect the metabolic outcomes.

Carrageenan hydrogel as a scaffold for skin-derived multipotent stromal cells delivery.

Carrageenan is a thermoreversible polymer of natural origin widely used in food and pharmaceutical industry that presents a glycosaminoglycan-like structure. Herein, we show that kappa-type carrageenan extracted by a semi-refined process from the red seaweed Kappaphycus alvarezii displayed both chemical and structural properties similar to a commercial carrageenan. Moreover, both extracted carrageenan hydrogel and commercial carrageenan hydrogel can serve as a scaffold for in vitro culture of human skin-derived multipotent stromal cells, demonstrating considerable potential as cell-carrier materials for cell delivery in tissue engineering. Skin-derived multipotent stromal cells cultured inside the carrageenan hydrogels showed a round shape morphology and maintained their growth and viability for at least one week in culture. Next, the effect of the extracted carrageenan hydrogel loaded with human skin-derived multipotent stromal cells was evaluated in a mouse model of full-thickness skin wound. Macroscopic and histological analyses revealed some pointed ameliorated features, such as reduced inflammatory process, faster initial recovery of wounded area, and improved extracellular matrix deposition. These results indicate that extracted carrageenan hydrogel can serve as a scaffold for in vitro growth and maintenance of human SD-MSCs, being also able to act as a delivery system of cells to wounded skin. Thus, evaluation of the properties discussed in this study contribute to a further understanding and specificities of the potential use of carrageenan hydrogel as a delivery system for several applications, further to skin wound healing.