huprine-y and 3-nitropropionic-acid

We have investigated the neuroprotective effects of (+/-)-huprine Y on excitotoxic lesions in rat cerebellar granule cells (CGCs). (+/-)-Huprine Y prevented cell death induced by 100 microM glutamate, as well as, 10 microM MK-801, a NMDA receptor antagonist, in a significant manner. On the other hand, intracellular calcium increase induced by NMDA (200 microM), measured by fura-2 fluorescence, was prevented by (+/-)-huprine Y with an EC(50) of 12.44 microM, which evidences the modulatory action of this compound on NMDA-induced calcium currents. In vivo, we have studied (+/-)-huprine Y neuroprotective effects on striatal lesions induced by the subacute administration of the mitochondrial toxin 3-nitropropionic acid (3-NP, 30 mg/kg, ip, for 10 days). We have assessed that both the behavioral and the morphological consequences of the lesion were prevented by pretreatment with (+/-)-huprine Y (2.5 mg/kg/twice a day, ip). Striatal gliosis induced by 3-NP treatment was prevented by (+/-)-huprine Y pretreatment, as demonstrated by the attenuation of both the increase in [(3)H]PK 11195 specific binding indicative of microgliosis and the expression of hsp27 kDa, a chaperone expressed mainly in astrocytes. In conclusion, (+/-)-huprine Y attenuated excitotoxic-induced lesions, both in vitro and in vivo, and further evidence is provided for the potential use of this compound in the prevention of neurodegenerative disorders.

Topics: Aminoquinolines; Animals; Binding, Competitive; Calcium; Cell Death; Cells, Cultured; Cerebellum; Corpus Striatum; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Gliosis; Glutamic Acid; Heat-Shock Proteins; Heterocyclic Compounds, 4 or More Rings; HSP27 Heat-Shock Proteins; Isoquinolines; Mice; Molecular Chaperones; Motor Activity; N-Methylaspartate; Neoplasm Proteins; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Neurotoxins; Nitro Compounds; Propionates; Rats