Evaluation of structural and neurochemical alterations caused by selective lesion of Locus coeruleus in the non-motor symptoms of 6-OHDA model of Parkinson's Disease

Abstract

Parkinson's disease (PD) is a chronic neurodegenerative and progressive disease, characterized by the loss of dopaminergic neurons of the substantia nigra (SN). Patients with PD present symptoms such as tremor at rest, muscle stiffness, bradykinesia, hypokinesia, and changes in posture and balance. The degeneration of the dopaminergic neurons is observed in PD, mostly in SNpc neurons, who send projections to the striatum area (nigrostriatal dopaminergic pathway), formed by the base nuclei- caudate and putamen. The SNpc neurodegeneration causes decrease on the dopamine levels and functional loss of these nuclei, and the reduction of approximately 70% to 80% of striatal dopamine, resulting on the motor manifestations mentioned above. In addition to SN, a proportion of noradrenergic neurons of the Locus Coeruleus (LC) also present significant degeneration in PD patients. Thus, strong evidence shows that the progression of the pathology, as well as the degeneration of brain nuclei in PD, follows a caudo-rostral way. Clinical studies in PD patients have shown that LC degeneration occurs before and to a greater extent than nigro-striatal dopaminergic neurons. Therefore, the aim of this project are to verify if the lesion of the catecholaminergic neurons of the LC could cause structural and neurochemical alterations in the hippocampus leading to alterations in spatial and attentional memory in the non-motor symptoms of 6-OHDA model of Parkinson's Disease. (AU)