Cortistatin as a Novel Multimodal Therapy for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a complex disorder characterized by the impairment of the dopaminergic nigrostriatal system. PD has duplicated its global burden in the last few years, becoming the leading neurological disability worldwide. Therefore, there is an urgent need to develop innovative approaches that target multifactorial underlying causes to potentially prevent or limit disease progression.

Placental transfer of NMDAR antibodies causes reversible alterations in mice.

Objective: To determine whether maternofetal transfer of NMDA receptor (NMDAR) antibodies has pathogenic effects on the fetus and offspring, we developed a model of placental transfer of antibodies.

Methods: Pregnant C57BL/6J mice were administered via tail vein patients' or controls' immunoglobulin G (IgG) on days 14-16 of gestation, when the placenta is able to transport IgG and the immature fetal blood-brain barrier is less restrictive to IgG crossing. Immunohistochemical and DiOlistic (gene gun delivery of fluorescent dye) staining, confocal microscopy, standardized developmental and behavioral tasks, and hippocampal long-term potentiation were used to determine the antibody effects.

Allosteric modulation of NMDA receptors prevents the antibody effects of patients with anti-NMDAR encephalitis.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disease characterized by a complex neuropsychiatric syndrome in association with an antibody-mediated decrease of NMDAR. About 85% of patients respond to immunotherapy (and removal of an associated tumour if it applies), but it often takes several months or more than 1 year for patients to recover. There are no complementary treatments, beyond immunotherapy, to accelerate this recovery.

Frequency and relevance of IgM, and IgA antibodies against MOG in MOG-IgG-associated disease.

Objective: To determine the frequency and relevance of IgM, and IgA antibodies against myelin oligodendrocyte glycoprotein (MOG) in MOG-IgG-associated disease.

Methods: Evaluation of IgM, and IgA MOG antibodies in serum of 120 patients with MOG-IgG (53 pediatric and 67 adults), and 114 patients with seronegative-MOG-IgG (35 children with first demyelinating syndrome, 20 adults with clinically isolated syndrome, and 59 adults with other diseases). Antibodies were examined by cell-based assays.

Lulling immunity, pain, and stress to sleep with cortistatin.

Cortistatin is a neuropeptide isolated from cortical brain regions, showing high structural homology and sharing many functions with somatostatin. However, cortistatin exerts unique functions in the central nervous and immune systems, including decreasing locomotor activity, inducing sleep-promoting effects, and deactivating inflammatory and T helper (TH )1/TH 17-driven responses in preclinical models of sepsis, arthritis, multiple sclerosis, and colitis. Besides its release by cortical and hippocampal interneurons, cortistatin is produced by macrophages, lymphocytes, and peripheral nociceptive neurons in response to inflammatory stimuli, supporting a physiological role of cortistatin in the immune and nociceptive systems.

Adrenomedullin protects from experimental autoimmune encephalomyelitis at multiple levels.

Adrenomedullin is a neuropeptide known for its cardiovascular activities and anti-inflammatory effects. Here, we investigated the effect of adrenomedullin in a model of experimental autoimmune encephalomyelitis (EAE) that mirrors chronic progressive multiple sclerosis. A short-term systemic treatment with adrenomedullin reduced clinical severity and incidence of EAE, the appearance of inflammatory infiltrates in spinal cord and the subsequent demyelination and axonal damage.

Paradoxical effect of cortistatin treatment and its deficiency on experimental autoimmune encephalomyelitis.

Cortistatin is a cyclic-neuropeptide produced by brain cortex and immune cells that shows potent anti-inflammatory activity. In this article, we investigated the effect of cortistatin in two models of experimental autoimmune encephalomyelitis (EAE) that mirror chronic and relapsing-remitting multiple sclerosis. A short-term systemic treatment with cortistatin reduced clinical severity and incidence of EAE, the appearance of inflammatory infiltrates in spinal cord, and the subsequent demyelination and axonal damage.