The role of locus coeruleus (LC) in the spatial memory in a non-motor symptoms of 6-OHDA model of Parkinson's Disease

• Grant number: 17/20420-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2018
• End date: June 30, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Ariadiny de Lima Caetano
• Grantee: Isabella Bacci Bustelli
• Host Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil

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. In addition to SN, a proportion of noradrenergic neurons of the Locus Coeruleus (LC) also present significant degeneration in PD patients. Thus, non-motor preclinical symptoms such as changes in sleep, depression and autonomic nervous system dysfunction appear before the motor symptoms in PD, being related to the neurodegeneration of the LC. Data from the literature showed that ventral tegmentar area (VTA) projection to the dorsal hippocampus promoted hippocampal reactivation during sleep and memory stabilization, but it was verified that only 10 % of this projection released dopamine, suggesting that another area could be responsible for the activation of dopaminergic receptors present in the hippocampus. Dopamine is removed from the hippocampal synapses by the norepinephrine transporter, indicating that it may be released by noradrenergic neurons. Further, LC stimulation has been shown to increase dopamine levels in the prefrontal cortex, suggesting that LC inputs are not purely noradrenergic but also dopaminergic in the dorsal hippocampus, and it might has an importance in spatial memory implicit attention . Therefore, the aim of this project is to verify if the selective lesion of the LC neurons is able to promote changes in the spatial memory in rats submitted to a non-motor symptoms of PD model by bilateral injection of 6-OHDA in the striatum.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OLIVEIRA, LUIZ M.; HENRIQUE, ELISANDRA; BUSTELLI, ISABELLA B.; NETTO, NELSON F. C.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.; CAETANO, ARIADINY L.. Depletion of hypothalamic hypocretin/orexin neurons correlates with impaired memory in a Parkinson's disease animal model. Experimental Neurology, v. 323, JAN 2020. (17/20420-5, 16/23281-3, 17/12266-6, 15/23376-1, 15/18842-3)