Cognitive impairment in an experimental model of Parkinson´s Disease

HERRERA M.; DEZA-PONZIO R.; BASMADJIAN M; OCCHIEPPO V.; MOLINA V.; BELLINI 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 is a neurodegenerative disorder that results from a progressive dopaminergic neuronal loss. It is considered a multifactorial condition due to the multiplicity of symptoms experienced by patients. While this condition is known for its characteristic motor deficits, patients also have wide variety non-motor symptoms, among them, impaired learning and memory deficits which severely affect their 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 experimental model of the neuropathology, the progression of working memory deficits and its correlation with the loss of dopaminergic neurons. METHODS: Adult male Wistar rats were stereotaxically injected with the neurotoxin 6OHDA in dorsal lateral striatum (DLS) or with the control solution of ascorbic saline. Independent groups of animals (12-15 rats per group) were tested only once in the behavioral tasks after 7, 14, 20 and 28 days. A group of animals were tested in the working memory task Y-maze and motor function was characterized using locomotor activity with amphetamine administration, stick and hot plate tests. After that, the rats were perfused and their brains processed for immunohistochemical of tyrosine hydroxylase (TH) in the substantia nigra (SN), DLS, dorsal hippocampus (CA1) and prefrontal cortex (PFC).RESULTS: Working memory deficits were observed in 6OHDA rats compared to Vehicle rats after 20 and 28 days of neurodegeneration (p<0.05). By the other hand, Motor deficits were increased at 28 days after lesion in 6OHDA (p<0.05) and we discarded these rats for cognitive performance consideration. At 7 and 15 days post lesion there were no significant changes in any behavioral task (p>0.05). In parallel, we observed that this early memory impairment occurring at a premotor 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 memory impairments without locomotor alterations 2) Knowledge of this neurodegenerative progression could result in potential new therapeutic strategies, which motivates us to further studies under this experimental model.