Dopaminergic Receptors as Neuroimmune Mediators in Experimental Autoimmune Encephalomyelitis.

The dopaminergic system plays an essential role in maintaining homeostasis between the central nervous system (CNS) and the immune system. Previous studies have associated imbalances in the dopaminergic system to the pathogenesis of multiple sclerosis (MS). Here, we examined the protein levels of dopaminergic receptors (D1R and D2R) in different phases of the experimental autoimmune encephalomyelitis (EAE) model. We also investigated if the treatment with pramipexole (PPX)-a dopamine D2/D3 receptor-preferring agonist-would be able to prevent EAE-induced motor and mood dysfunction, as well as its underlying mechanisms of action. We report that D2R immunocontent is upregulated in the spinal cord of EAE mice 14 days post-induction. Moreover, D1R and D2R immunocontents in lymph nodes and the oxidative damage in the spinal cord and striatum of EAE animals were significantly increased during the chronic phase. Also, during the pre-symptomatic phase, axonal damage in the spinal cord of EAE mice could already be found. Surprisingly, therapeutic treatment with PPX failed to inhibit the progression of EAE. Of note, PPX treatment inhibited EAE-induced depressive-like while failed to inhibit anhedonic-like behaviors. We observed that PPX treatment downregulated IL-1ß levels and increased BNDF content in the spinal cord after EAE induction. Herein, we show that a D2/D3 receptor-preferred agonist mitigated EAE-induced depressive-like behavior, which could serve as a new possibility for further clinical trials on treating depressive symptoms in MS patients. Thus, we infer that D2R participates in the crosstalk between CNS and immune system during autoimmune and neuroinflammatory response induced by EAE, mainly in the acute and chronic phase of the disease.

Evaluation of effect of cyclosporine A on the bone tissue with induced periodontal disease to ligature in rats.

The administration of cyclosporine A (CsA) has been associated with significant bone loss and increased bone remodeling. The present investigation was designed to evaluate the effects of CsA on alveolar bone of rats subjected to experimental periodontitis, using histomorphometric and histological analysis. Twenty-four rats were divided into groups with 6 animals each: 1, control; 2, rats with ligature around the lower first molars; 3, rats with ligature around the lower first molars and that were treated with 10 mg CsA/kg of body weight/d; and 4, rats treated with 10 mg CsA/kg of body weight/d. At the end of 30 days, rats were humanely killed and subjected to a histological processing, with analysis of the distance cemento-enamel junction and alveolar bone crest, bone area, eroded bone area, and cemento surface. All of them were assessed at the mesial region of the alveolar bone. The CsA therapy combined with ligature placement decreased bone area and increased the eroded bone area around the tooth surface. The results at the histological analysis showed the same combination and changes. Therefore, in spite of the lack of a direct effect on the alveolar bone height, the CsA therapy intensified the imbalance of the alveolar bone homeostasia in a rat model of experimental periodontitis.