| Grant number: | 17/13560-5 |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| Start date: | March 01, 2018 |
| End date: | April 30, 2021 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Agreement: | Coordination of Improvement of Higher Education Personnel (CAPES) |
| Principal Investigator: | Norberto Cysne Coimbra |
| Grantee: | Priscila Medeiros de Freitas |
| Host Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
Abstract Parkinson's disease (PD) is a progressive disorder of movement associated with the dopaminergic depletion of the substantia nigra, pars compacta (SNpc). The basal nuclei and motor cortex connexions impairments lead to clinical manifestations like tremor, postural stiffness, bradykinesia and postural instability. However, non-motor symptoms, for example, depression, anxiety, cognitive changes, olfactory disorders and chronic pain may also be present in PD. In fact, manifestations of non-motor symptoms affect the quality of life of patients with PD. Recent studies suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN) could improve the motor, pain, and emotional state of PD patients. Indeed, the pathophysiology and Neuropsychopharmacological mechanisms of PD symptoms need to be better clarified. Therefore, we will evaluate the motor and non-motor symptoms of parkinsonoid syndrome using the animal model of PD with microinjections of the 6-hydroxydopamine (6-OHDA) neurotoxin or sham procedure (without neurotoxin) in the Striatum. The present project will be divided as follows: 1st: Neuroanatomical study: to evaluate the anatomic connections between STN with motor areas [as motor cortex (M1) and basal nuclei] and non-motor areas [as medial prefrontal cortex (mPFC)] will be microinjected BDA 3.000 in STN. 2nd: Neuroelectrophysiological study: we will use the multiuser equipment (Thomas Recording) to stimulate the STN and simultaneously register the neuronal activity of M1 and mPFC [cingulate cortex (Cg1), prelimbic (PrL) and infralimbic (IFL)] in lesioned animals with 6-OHDA or sham. 3rd: Neurophysiological study: To evaluate the effect of the STN neurostimulation on the motor and non-motor aspects of PD, the electrical stimulus (DBS at 20¼A or 100¼A for 15s) in different subareas (motor and non-motor) of the NST in animals treated with or without 6-OHDA. Thus, motor behaviours, like apomorphine-induced rotation test and cylinder test will be performed. The experiments related to non-motor behaviour, such as olfactory discrimination test (sensory), sucrose preference test (depression), recognition test (attention and memory), von Frey test (mechanical allodynia) and acetone test (sensitivity to cold) will also be performed. In order to evaluate the effect of cannabidiol (CBD) treatment on the motor and non-motor components of PD, the behavioural tests mentioned before will be carried out after the pretreatment of the STN with CBD (at 15, 30 and 60 nmol) in an experimental model of Parkinson's disease in Wistar rats. (AU) | |
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