Neuroscience
-
Remyelination is common under physiological conditions and usually occurs as a response to a pathological demyelinating event. Its potentiation is an important goal for the development of therapies against pathologies such as multiple sclerosis and white matter injury. Visualization and quantification in vivo of demyelination and remyelination processes are essential for longitudinal studies that will allow the testing and development of pro-myelinating strategies. ⋯ Daily systemic β-CCB administration for 2 weeks in lesioned animals increased FA and decreased λ⊥, suggesting an improvement in myelination, which was supported by histological analysis. This study shows that structural changes in the demyelination-remyelination of the caudal cerebellar peduncle (DRCCP) model can be monitored longitudinally by MRI, and it suggests that remyelination is enhanced by β-CCB treatment. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.
-
Differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs) is a key event for axonal myelination in the central nervous system (CNS). Several growth factors and neurotransmitters like GABA are postulated as important regulators of that process, and different protein kinases may also participate in OL differentiation and myelination. However, the molecular mechanisms underlying the regulation of myelination by neurotransmitters are only partially known. ⋯ None of these effects are mediated by the GABAAR agonist muscimol. Together, these results highlight the relevance of the GABAergic system in OL differentiation, and indicate that this functional role is mediated through GABABR involving the participation of Src-family kinases. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.
-
In the CNS, chemokines and chemokine receptors are involved in pleiotropic physiological and pathological activities. Several evidences demonstrated that chemokine signaling in the CNS plays key homeostatic roles and, being expressed on neurons, glia and endothelial cells, chemokines mediate the bidirectional cross-talk among parenchymal cells. ⋯ In this review we summarize the evidence that chemokines (CXCL12, CX3CL1, CXCL16 and CCL2) modulate neuroprotective processes upon different noxious stimuli and participate to orchestrate neurons-microglia-astrocytes action to preserve and limit brain damage. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.
-
Myasthenia gravis (MG) is a relatively rare neurological disease that is usually associated with antibodies to the acetylcholine receptor (AChR). These antibodies (Abs) cause loss of the AChRs from the neuromuscular junction (NMJ), resulting in muscle weakness that can be life-threatening. Another form of the disease is caused by antibodies to muscle specific kinase (MuSK) that result in impaired AChR clustering and numbers at the NMJ, and may also interfere with presynaptic adaptive mechanisms. ⋯ All four conditions can be diagnosed by specific clinical features, electromyography and serum antibody tests, and can be treated effectively by a combination of pharmacological approaches and procedures that reduce the levels of the IgG antibodies. They form the first of a spectrum of diseases in which serum autoantibodies bind to extracellular domains of neuronal proteins throughout the nervous system and lead to constellations of clinical features including paralysis, sensory disturbance and pain, memory loss, seizures, psychiatric disturbance and movement disorders. This review will briefly summarize the ways in which this field has developed, since the 1970s when considerable contributions were made in Ricardo Miledi's laboratory at UCL.