6-HYDROHYDOPAMINE DECREASES INTRACELULLAR ALDEHYDE DEHYDROGENASE 2: IMPLICATIONS FOR THE NEUROTOXICITY OF PARKINSON´S DISEASE

DEZA PONZIO, ROMINA; HERRERA, MACARENA LORENA; MARCHESE, NATALIA ANDREA; BASMADJIAN, OSVALDO MARTÍN; BELLINI, M.J.; MOLINA, VICTOR; VIRGOLINI, MIRIAM; HEREÑÚ, C.

Florianopolis

Congreso; International Neurotoxicology Association and Neurotoxicity Society Meeting 2017; 2017

International Neurotoxicology Association and Neurotoxicity Society

BACKGROUND: Parkinson?s disease (PD) is the second most common neurodegenerative disorder and is characterized pathologically by the loss of dopaminergic neurons in the substantia nigra. Although motor symptoms are the main clinical features of PD, increasing evidence has shown that PD patients also have non-motor symptoms, where cognitive dysfunction is one of the most common and devastating in this neuropathology. Among the different hypothesis related to PD etiology, an abnormal aldehyde dehydrogenase 2 (ALDH2) functionality in neurotransmitter degradation that leads to the accumulation of neurotoxic metabolites such as DOPAL and DOPEGAL. These molecules have been associated with neuronal cell death and neurodegeneration.OBJECTIVES: In this study we aimed to evaluate ALDH2 expression and cognitive function in a 6OHDA animal model of PD.METHODS: Male Wistar rats were bilaterally injected in dorsal striatum (CPu) with either the neurotoxicant (6OHDA rats) or vehicle (SHAM rats). Twenty days after the lesion the animals were tested for short-term spatial memory with a modified version of Y-maze test. At the end of the study the rats were perfused, their brains fixed and immunohistochemistry performed for TH and ALDH2 in CPu, substantia nigra (SN), dorsal hippocampus (CA1) and prefrontal cortex (PFC). All data were compared by Student´s t-test and 2-way ANOVA (p<0.05 considered as statistically significant)RESULTS: At the behavioral level we first observed that both groups of rats made a similar (p>0.05) number of visits to the two available arms during the training phase indicating no baseline differences between them. During the test session, the results revealed that only the control rats spent significantly more time in the novel arm in comparison to chance level (33% of time) (p<0.05), whereas the 6-OHDA-treated rats spent similar time exploring the three arms. The observed differences between groups were unrelated to alterations of locomotion since both groups made a similar (p>0.05) total number of entries in all the arms during the test session. At the cellular level, and as expected, 6OHDA treatment induced a reduction in TH positive dopaminergic neurons in the brain areas involved in nigrostratial pathway (CPu and SN) (p<0.05). Interestingly, we also observed a reduction in ALDH2 expression in 6OHDA rats in CPu, SN, CA1 and CPF compared to the SHAM rats (p<0.05).CONCLUSION: Our results suggest that a reduction in TH immunostaining is related to the cognitive dysfunction that we observed in this experimental animal model of PD. Moreover, the decreased ALDH2 expression may be associated to the neurotoxicity and neurodegeneration characteristic of this model.