RESUMO
Studies with multiple sclerosis patients and animal models of experimental autoimmune encephalomyelitis (EAE) implicate adenosine and adenosine receptors in modulation of neuroinflammation and brain injury. Although the involvement of the A(1) receptor has been recently demonstrated, the role of the adenosine A(2A) receptor (A(2A)R) in development of EAE pathology is largely unknown. Using mice with genetic inactivation of the A(2A) receptor, we provide direct evidence that loss of the A(2A)R exacerbates EAE pathology in mice. Compared with wild-type mice, A(2A)R knockout mice injected with myelin oligodendroglia glycoprotein peptide had a higher incidence of EAE and exhibited higher neurological deficit scores and greater decrease in body weight. A(2A)R knockout mice displayed increased inflammatory cell infiltration and enhanced microglial cell activation in cortex, brainstem, and spinal cord. In addition, demyelination and axonal damage in brainstem were exacerbated, levels of Th1 cytokines increased, and Th2 cytokines decreased. Collectively, these findings suggest that extracellular adenosine acting at A(2A)Rs triggers an important neuroprotective mechanism. Thus, the A(2A) receptor is a potential target for therapeutic approaches to multiple sclerosis.
Assuntos
Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Encefalomielite Autoimune Experimental/complicações , Regulação da Expressão Gênica/genética , Microglia/patologia , Receptor A2A de Adenosina/genética , Antagonistas do Receptor A1 de Adenosina/farmacocinética , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Axônios/patologia , Lesões Encefálicas/complicações , Proliferação de Células , Células Cultivadas , Córtex Cerebral/patologia , Citocinas/metabolismo , Doenças Desmielinizantes/etiologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Filtração , Citometria de Fluxo , Adjuvante de Freund/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Glicoproteína Mielina-Oligodendrócito/toxicidade , Fragmentos de Peptídeos/toxicidade , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , RNA Mensageiro/metabolismo , Receptor A2A de Adenosina/deficiência , Medula Espinal/patologia , Baço/citologia , Estatísticas não Paramétricas , Trítio/farmacocinética , Xantinas/farmacocinéticaRESUMO
In the title compound, [Cd(C14H10NO3)2(H2O)2], which crystallizes with Z = 4 in the space group C2c, the Cd atom is located on a twofold rotation axis and coordinated by six O atoms from two water molecules and two carboxylate groups of two planar 4-(2-hydroxybenzylideneamino)benzoate ligands, with a dihedral angle of 85.6 (1) degrees between them. Strong O-H...O hydrogen bonding in the coordination sphere, together with pi-pi stacking interactions, assemble the molecules into two-dimensional layers.
Assuntos
Compostos de Benzilideno/química , Cádmio/química , Compostos Organometálicos/química , Cristalografia por Raios X , Ligação de HidrogênioRESUMO
In the title compound, [Cu(C14H9NO3)(H2O)2], which crystallizes with Z = 18 in the space group R-3, pairs of complexes are linked into dimers by three O-H...O hydrogen bonds. Strong O-H...O hydrogen bonds link the dimers into one-dimensional chains that further assemble into tubes through pi-pi and C-H...pi interactions.
