Neuroprotective effects of (+/-)-huprine Y on in vitro and in vivo models of excitoxicity damage.

Abstract

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.

• Authors: Anna M Canudas, David Pubill, Francesc X Sureda, Ester Verdaguer, Pelayo Camps, Diego Muñoz-Torrero, Andrés Jiménez, Antoni Camins, Mercè Pallàs
• Journal: Experimental neurology (Exp Neurol) Vol. 180 Issue 2 Pg. 123-30 (Apr 2003) ISSN: 0014-4886 [Print] United States
• PMID: 12684026 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoquinolines
• HSP27 Heat-Shock Proteins
• Heat-Shock Proteins
• Heterocyclic Compounds, 4 or More Rings
• Hsbp1 protein, mouse
• Hspb1 protein, rat
• Isoquinolines
• Molecular Chaperones
• Neoplasm Proteins
• Neuroprotective Agents
• Neurotoxins
• Nitro Compounds
• Propionates
• huprine Y
• Glutamic Acid
• N-Methylaspartate
• 3-nitropropionic acid
• Calcium
• PK 11195

Topics

• Aminoquinolines (pharmacology)
• Animals
• Binding, Competitive (drug effects)
• Calcium (metabolism)
• Cell Death (drug effects)
• Cells, Cultured
• Cerebellum (cytology)
• Corpus Striatum (drug effects, pathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Gliosis (chemically induced, prevention & control)
• Glutamic Acid (toxicity)
• HSP27 Heat-Shock Proteins
• Heat-Shock Proteins
• Heterocyclic Compounds, 4 or More Rings (pharmacology)
• Isoquinolines (pharmacokinetics)
• Mice
• Molecular Chaperones
• Motor Activity (drug effects)
• N-Methylaspartate (pharmacology)
• Neoplasm Proteins (biosynthesis)
• Neurodegenerative Diseases (chemically induced, pathology, prevention & control)
• Neurons (cytology, drug effects)
• Neuroprotective Agents (pharmacology)
• Neurotoxins (toxicity)
• Nitro Compounds
• Propionates
• Rats