Objectives: This narrative review article provides an overview on the involvement of microglia and the hypothalamic-pituitary-adrenal (HPA) axis in the pathophysiology of depression, as well investigates the mutual relationship between these two entities: how microglial activation can contribute to the dysregulation of the HPA axis, and vice versa. Methods: Relevant studies and reviews already published in the Pubmed electronic database involving the themes microglia, HPA axis and depression were used to meet the objectives. Results: Exposition to stressful events is considered a common factor in the mechanisms proposed to explain the depressive disorder. Stress can activate microglial cells, important immune components of the central nervous system (CNS). Moreover, another system involved in the physiological response to stressors is the hypothalamic-pituitary-adrenal (HPA) axis, the main stress response system responsible for the production of the glucocorticoid hormone (GC). Also, mediators released after microglial activation can stimulate the HPA axis, inducing production of GC. Likewise, high levels of GCs are also capable of activating microglia, generating a vicious cycle. Conclusion: Immune and neuroendocrine systems seems to work in a coordinated manner and that their dysregulation may be involved in the pathophysiology of depression since neuroinflammation and hypercortisolism are often observed in this disorder.

The present study investigated the effects of oral administration of annatto carotenoids (bixin (BIX) and norbixin (NBIX)) on glucose levels, lipid profiles, and oxidative stress parameters in streptozotocin (STZ)-induced diabetic rats. Animals were treated for 30 days in the following groups: nondiabetic control, diabetic vehicle, diabetic 10 mg/kg BIX, diabetic 100 mg/kg BIX, diabetic 10 mg/kg NBIX, diabetic 100 mg/kg NBIX, diabetic metformin, and diabetic insulin. Blood glucose, LDL cholesterol, and triglyceride levels were reduced in the diabetic rats treated with BIX. BIX treatment prevented protein oxidation and nitric oxide production and restored superoxide dismutase activity. NBIX treatment did not change most parameters assessed, and at the highest dose, it increased LDL cholesterol and triglycerides levels and showed prooxidant action (increased protein oxidation and nitric oxide levels). These findings suggested that BIX could have an antihyperglycemic effect, improve lipid profiles, and protect against damage induced by oxidative stress in the diabetic state. Because NBIX is a water-soluble analog of BIX, we propose that lipophilicity is crucial for the protective effect of annatto carotenoids against streptozotocin-induced diabetes.

Headaches are frequently described in progressive multiple sclerosis (PMS) patients, but their mechanism remains unknown. Transient receptor potential ankyrin 1 (TRPA1) was involved in neuropathic nociception in a model of PMS induced by experimental autoimmune encephalomyelitis (PMS-EAE), and TRPA1 activation causes periorbital and facial nociception. Thus, our purpose was to observe the development of periorbital mechanical allodynia (PMA) in a PMS-EAE model and evaluate the role of TRPA1 in periorbital nociception. Female PMS-EAE mice elicited PMA from day 7 to 14 days after induction. The antimigraine agents olcegepant and sumatriptan were able to reduce PMA. The PMA was diminished by the TRPA1 antagonists HC-030031, A-967079, metamizole and propyphenazone and was absent in TRPA1-deficient mice. Enhanced levels of TRPA1 endogenous agonists and NADPH oxidase activity were detected in the trigeminal ganglion of PMS-EAE mice. The administration of the anti-oxidants apocynin (an NADPH oxidase inhibitor) or alpha-lipoic acid (a sequestrant of reactive oxygen species), resulted in PMA reduction. These results suggest that generation of TRPA1 endogenous agonists in the PMS-EAE mouse model may sensitise TRPA1 in trigeminal nociceptors to elicit PMA. Thus, this ion channel could be a potential therapeutic target for the treatment of headache in PMS patients.