Stress during fetal life increases the risk of affective and immune disorders later in life. The altered peripheral immune response caused by prenatal stress may impact on brain function by the modification of local inflammation. In this study we have explored whether prenatal stress results in alterations in the immune response in the hippocampus of female mice during adult life.

The glucagon-like peptide-1 (GLP-1) is a pleiotropic hormone well known for its incretin effect in the glucose-dependent stimulation of insulin secretion. However, GLP-1 is also produced in the brain and displays a critical role in neuroprotection and inflammation by activating the GLP-1 receptor signaling pathways. Several studies in vivo and in vitro using preclinical models of neurodegenerative diseases show that GLP-1R activation has anti-inflammatory properties. This review explores the molecular mechanistic action of GLP-1 RAS in relation to inflammation in the brain. These findings update our knowledge of the potential benefits of GLP-1RAS actions in reducing the inflammatory response. These molecules emerge as a potential therapeutic tool in treating neurodegenerative diseases and neuroinflammatory pathologies.

Using pharmacological tools, a role for opioid receptors in the regulation of food intake has been documented. However, the involvement of specific receptor subtypes remains questionable, and little information is available regarding a role for opioid receptors in energy metabolism. Using adult male mice lacking the μ-opioid receptor (MOR) gene (MOR^−/−), we show that the MOR is not essential for the maintenance of normal levels of ad libitum food intake but does modulate the efficiency of energy storage during high-fat diets through the regulation of energy partitioning. When fed a regular diet, MOR^−/− mice displayed only subtle alterations in energy homeostasis, suggesting a relative overuse of fat as a fuel source in the fed state. When fed a high-fat diet, MOR^−/− mice were resistant to obesity and impaired glucose tolerance, despite having similar energy intake to wild-type mice. This resistance to obesity was associated with a strong induction of the expression of key mitochondrial enzymes involved in fatty acid oxidation within skeletal muscle. This metabolic role of the MOR, which is consistent with the properties of a “thrifty gene,” suggests that the MOR pathway is a potential target for pharmacological intervention in the treatment of obesity associated with the intake of fatty diets.

It has been previously reported that the neuroprotective hormone oestradiol reduces microglia inflammatory activity. The objective of this study was to test whether two selective oestrogen receptor modulators, tamoxifen and raloxifene, modulate in vivo the activation of microglia induced by the peripheral administration of lipopolysaccharide (LPS). Activation of microglia was assessed in the white matter of the cerebellum using immunoreactivity for major histocompatability complex-II. Oestradiol, tamoxifen and raloxifene decreased microglia activation induced by LPS in male and ovariectomized female rats, although the doses of oestradiol that were effective in decreasing microglia reactivity were not the same in both sexes. Tamoxifen reduced microglia activation in all experimental groups at all doses tested (0.5–2 mg/kg b.w.) while raloxifene lost its anti-inflammatory activity at the higher dose tested (2 mg/kg b.w). In addition, raloxifene had per se a moderate pro-inflammatory activity in the brain of control female rats and its anti-inflammatory activity was partially impaired in female animals after 1 month of deprivation of ovarian hormones. Spots of oestrogen receptor (ER)-α immunoreactivity were detected in the soma and cell processes of microglia. Treatment with LPS, oestradiol or tamoxifen induced an increase of ER-α immunoreactive spots in the perikaryon of microglia, while oestradiol antagonized the effect of LPS. The results indicate that some oestrogenic compounds decrease brain inflammation by a mechanism that may involve ERs expressed by microglia. The findings support the potential therapeutic role of oestrogenic compounds as protective anti-inflammatory agents for the central nervous system.