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 MARTIN; BELLINI, MARÍA JOSÉ; MOLINA, VICTOR ALEJANDRO; VIRGOLINI, MIRIAM BEATRIZ; HEREÑÚ, CLAUDIA BEATRIZ

Florianópolis

Congreso; 2017 Joint Meeting of the Neurotoxicity Society and the International Neurotoxicology Association; 2017

Neurotoxicity Society and International Neurotoxicology Association

BACKGROUND: Parkinson?s disease (PD) is the second most common neurodegenerativedisorder and is characterized pathologically by the loss of dopaminergic neurons in thesubstantia nigra. Although motor symptoms are the main clinical features of PD, increasingevidence has shown that PD patients also have non-motor symptoms, where cognitivedysfunction is one of the most common and devastating in this neuropathology. Among thedifferent hypothesis related to PD etiology, an abnormal aldehyde dehydrogenase 2(ALDH2) functionality in neurotransmitter degradation that leads to the accumulation ofneurotoxic metabolites such as DOPAL and DOPEGAL. These molecules have beenassociated with neuronal cell death and neurodegeneration.OBJECTIVES: In this study we aimed to evaluate ALDH2 expression and cognitivefunction in a 6OHDA animal model of PD.METHODS: Male Wistar rats were bilaterally injected in dorsal striatum (CPu) with eitherthe neurotoxicant (6OHDA rats) or vehicle (SHAM rats). Twenty days after the lesion theanimals 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 immunohistochemistryperformed 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-wayANOVA (p0.05) number of visits to the two available arms during the training phase indicating nobaseline differences between them. During the test session, the results revealed that onlythe control rats spent significantly more time in the novel arm in comparison to chancelevel (33% of time) (p0.05) total number of entriesin all the arms during the test session. At the cellular level, and as expected, 6OHDAtreatment induced a reduction in TH positive dopaminergic neurons in the brain areasinvolved in nigrostratial pathway (CPu and SN) (p