6-Hydroxydopamine decreases brain aldehyde dehydrogenase 2 (ALDH2) expression: Implications for neurotoxicity in a Parkinson´s disease model

DEZA-PONZIO R; HERRERA M; VIRGOLINI MB,; HERENNU C

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

Parkinson?s disease (PD) is the second most common neurodegenerative disorder and is characterizedpathologically by the loss of dopaminergic neurons in the substantia nigra (SN). Although motor symptoms arethe main clinical features of PD, increasing evidence has shown that PD patients also have non-motorsymptoms, where cognitive dysfunction is one of the most common and devastating in this neuropathology.Among the different hypothesis related to PD etiology, an abnormal ALDH2 functionality in neurotransmitterdegradation that leads to the accumulation of neurotoxic metabolites such as DOPAL and DOPEGAL has beendescribed. 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 6-hydroxydopamine (6-OHDA) animal model of PD. METHODS: Male Wistar rats were bilaterally injected indorsal striatum (CPu) with either the neurotoxicant (6-OHDA rats) or vehicle (SHAM rats). Twenty days afterthe lesion the animals were tested for short-term spatial memory with a modified version of Y-maze test. At theend of the study the rats were perfused, their brains fixed and immunohistochemistry performed for TH andALDH2 in CPu, SN, dorsal hippocampus (CA1) and prefrontal cortex (PFC). All data were compared byStudent´s t-test and 2-way ANOVA (p0.05) number of visits to the two availablearms during the training phase indicating no baseline differences between them. During the test session, theresults revealed that only the control rats spent significantly more time in the novel arm in comparison tochance level (33% of time) (p0.05) total number of entries in all the arms during the test session. At the cellular level, andas expected, 6-OHDA treatment induced a reduction in TH positive dopaminergic neurons in the brain areasinvolved in nigrostratial pathway (CPu and SN) (p