6-HYDROXYDOPAMINE DECREASES BRAIN ALDEHYDE DEHYDROGENASE 2 (ALDH2) EXPRESSION: IMPLICATIONS FOR NEUROTOXICITY IN A PARKINSON´S DISEASE MODEL

DEZA-PONZIO R.; HERRERA M.; MARCHESE N.; BASMADJIAN M; BELLINI M,; MOLINA V.; VIRGOLINI M.; HEREÑÚ CB

Florianópolis

Encuentro; International Neurotoxicology Association and Neurotoxicity Society Joint Meeting 2017; 2017

International Neurotoxicology Association and Neurotoxicity Society

BACKGROUND: Parkinson?s disease (PD) is the second most common neurodegenerativedisorder and is characterized pathologically by the loss of dopaminergic neurons in thesubstantia nigra (SN). Although motor symptoms are the main clinical features of PD,increasing evidence has shown that PD patients also have non-motor symptoms, wherecognitive dysfunction is one of the most common and devastating in this neuropathology.Among the different hypothesis related to PD etiology, an abnormal ALDH2 functionalityin neurotransmitter degradation that leads to the accumulation of neurotoxic metabolitessuch as DOPAL and DOPEGAL has been described. These molecules have been associatedwith neuronal cell death and neurodegeneration.OBJECTIVES: In this study we aimed to evaluate ALDH2 expression and cognitivefunction in a 6-hydroxydopamine (6-OHDA) animal model of PD.METHODS: Male Wistar rats were bilaterally injected in dorsal striatum (CPu) with eitherthe neurotoxicant (6-OHDA 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, SN, dorsal hippocampus (CA1) and prefrontalcortex (PFC). All data were compared by Student´s t-test and 2-way ANOVA (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, 6-OHDAtreatment induced a reduction in TH positive dopaminergic neurons in the brain areasinvolved in nigrostratial pathway (CPu and SN) (p