Cognitive impairment in an experimental model of Parkinson´s Disease

HERRERA, MACARENA LORENA; DEZA PONZIO, ROMINA; BASMADJIAN, OSVALDO MARTIN; OCCHIEPPO, VICTORIA BELÉN; MOLINA, VICTOR ALEJANDRO; BELLINI, MARÍA JOSÉ; HEREÑÚ, CLAUDIA

Florianópolis

Congreso; Joint Meeting NTS & INA: Neurotoxicity Society and International Neurotoxicology Association; 2017

Neurotoxicity Society and International Neurotoxicology Association

BACKGROUND: Parkinson´s disease is a neurodegenerative disorder that results from a progressivedopaminergic neuronal loss. It is considered a multifactorial condition due to the multiplicity of symptomsexperienced by patients. While this condition is known for its characteristic motor deficits, patients also havewide variety non-motor symptoms among them, impaired learning and memory deficits which severely affecttheir quality of life. These non-motor symptoms result from the dysfunction of interconnected systems,including the striatum, the neocortex and the hippocampus. OBJECTIVES: To determine, in an experimentalmodel of the neuropathology, the progression of working memory deficits and its correlation with the loss ofdopaminergic neurons. METHODS: Adult male Wistar rats were stereotaxically injected with the neurotoxin6OHDA in dorsal lateral striatum (DLS) or with the control solution of ascorbic saline. Independent groups ofanimals (12-15 rats per group) were tested only once in the behavioral tasks after 7, 14, 20 and 28 days. Agroup of animals were tested in the working memory task Y-maze and motor function was characterized usinglocomotor activity with amphetamine administration, stick and hot plate tests. After that, the rats were perfusedand their brain processed for immunohistochemical of tyrosine hydroxylase (TH) in the substantia nigra (SN),DLS, dorsal hippocampus (CA1) and prefrontal cortex (PFC). RESULTS: Working memory deficits wereobserved in 6OHDA rats compared to Vehicle rats after 20 and 28 days of neurodegeneration (p<0.05). By theother hand, motor deficits were increased at 28 days after lesion in 6OHDA (p<0.05) and we discarded theserats for cognitive performance consideration. At 7 and 15 days post lesion there were no significant changes inany behavioral task (p>0.05). In parallel, we observed that this early memory impairment occurring at apremotor stage of PD is associated with a partial lesion of the nigrostriatal dopaminergic system.CONCLUSION: 1) bilateral intra-DLS injection of 6-OHDA was sufficient to cause working memoryimpairments without locomotor alterations 2) Knowledge of this neurodegenerative progression could result inpotential new therapeutic strategies, which motivates us to further studies under this experimental model.