Seminário: Nitric oxide modulation of the basal ganglia circuitry: therapeutic implication for Parkinson’s disease and sensorimotor disorders

Data:  20/07/16 (Quarta-Feira)

Hora:  12h50

Local: Bloco Beta, Auditório A005 (campus São Bernardo do Campo)

Palestrante: Dra. Elaine Del-Bel

 

Tema: Nitric oxide modulation of the basal ganglia circuitry: therapeutic implication for Parkinson’s disease and sensorimotor disorders.

Several recent studies have emphasized a crucial role for the nitrergic system inmovement control and the pathophysiology of the basal ganglia. These observations

are supported by anatomical evidence demonstrating the presence of nitric oxide synthase (NOS) in all the basal ganglia nuclei. In fact, nitrergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamic nuclei. These brain areas contain a high expression of nitric oxide (NO)-producing neurons, with the striatum having the greatest number, together with important NO afferent input. In this talk, the new avenues that the increasing knowledge of NO in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson’s disease a movement disorder, will be discussed. For example, inhibition of striatal NO/guanosine monophosphate signal pathway by nitric oxide synthase (NOS) seems to be effective in L-DOPA- induced dyskinesia. The effect is dose-dependent, does not suffer tolerance nor interferes with L-DOPA positive motor effects. Hemi-Parkinsonian rats presenting L-DOPA- induced dyskinesia show increased expression in the striatum of neuronal NOS (nNOS) mRNA nNOS and inducible NOS (iNOS) protein, FosB/ΔFosB and inflammatory markers as astrocytes, microglia and COX2. Striatal COX2 co-localized with choline-acetyltransferase, calbindin and DARPP-32 (dopamine-cAMP- regulated phosphoprotein-32), neuronal markers of GABAergic neurons. These changes are decreased by administration of nNOS preferential inhibitor, raising the possibility that the anti-dyskinetic effects of these drugs would include interference in NO-mediated processes. However, the results of experimental studies have to be interpreted with caution given the complexities of nitrergic signalling and the limitations of animal models. Nevertheless, the NO system represents a promising pharmacological intervention for treating Parkinson's disease and related disorders.

 

 

Elaine Del-Bel

É professora de Fisiologia na FORP-Universidade de São Paulo desde outubro de 2015. Em 2013 foi indicada como professora Titular em Fisiologia. Possui mestrado e doutorado (1988) em Farmacologia pela Faculdade de Medicina da Universidade de São Paulo em Ribeirão Preto.

O pós-doutorado foi realizado na Inglaterra em Manchester. Realizou estágios curtos em países com os quais possui projetos em colaboração: Prof. John H Nicholls, Itália Escuola Internazionale di Studi Superiori (SISSA-Trieste); Prof. Walter Sthumer- Instituto Max Planck for Experimental Medicine, Göttingen, Alemanha; Dra. Rita Raisman Vozari INSERM, Hopital de La Salpétriére, Paris, França; Prof. Harry Steinbuch, University of Maastrichth Holanda; Prof. Frank Kirchhoff- Universidade de Homburg- Saarland-Germany.

Tem experiência na área de Bioquímica, Farmacologia e Fisiologia, com ênfase no sistema nervoso central. Atualmente, os estudos concentram-se em modelos experimentais da doença de Parkinson e nas conseqüências do tratamento com o precursor da Dopamina (Levodopa).

 

 

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