Dravet syndrome (DS) is an epileptic encephalopathy caused by mutations in the
gene encoding the α1 subunit of the Nav1.1 sodium channel, which is associated with recurrent and generalized seizures, ...even leading to death. In experimental models of DS, histological alterations have been found in the brain; however, the retina is a projection of the brain and there are no studies that analyze the possible histological changes that may occur in the disease. This study analyzes the retinal histological changes in glial cells (microglia and astrocytes), retinal ganglion cells (RGCs) and GABAergic amacrine cells in an experimental model of DS (Syn-Cre/Scn1a
) compared to a control group at postnatal day (PND) 25. Retinal whole-mounts were labeled with anti-GFAP, anti-Iba-1, anti-Brn3a and anti-GAD65/67. Signs of microglial and astroglial activation, and the number of Brn3a+ and GAD65+67+ cells were quantified. We found retinal activation of astroglial and microglial cells but not death of RGCs and GABAergic amacrine cells. These changes are similar to those found at the level of the hippocampus in the same experimental model in PND25, indicating a relationship between brain and retinal changes in DS. This suggests that the retina could serve as a possible biomarker in DS.
Abstract Melanoma is the most aggressive form of skin cancer, it originates from melanocytes and its incidence has increased in the last decade. Recent advances in the understanding of the underlying ...biology of the progression of melanoma have identified key signalling pathways that are important in promoting melanoma tumourigenesis, thus providing dynamic targets for therapy. One such important target identified in melanoma tumour progression is the Nuclear Factor-κB (NF-κB) pathway. In vitro studies have shown that NF-κB binding is constitutively elevated in human melanoma cultures compared to normal melanocytes. It has been found that a short cell-permeable peptide spanning the IKK-β NBD, named NBD peptide, disrupted the association of NEMO with IKKs in vitro and blocked TNFα-induced NF-κB activation in vivo. In the present study we investigated the effect of the NBD peptide on NF-κB activity and survival of A375 human melanoma cells. We found that NBD peptide is able to inhibit the proliferation of A375 cells, which present constitutively elevated NF-κB levels. Inhibition of cell proliferation by NBD peptide was associated with direct inhibition of constitutive NF-κB DNA-binding activity and induction of apoptosis by activation of caspase-3 as confirmed by the cleavage and consequently inactivation of poly (ADP ribose) polymerase (PARP-1) known as the best marker of this process.
