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Effect of deep brain stimulation and cannabidiol treatment in the subthalamic nucleus on the motors and non-Motors symptoms in the experimental model of Parkinson Disease

Grant number: 17/13560-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2018
Effective date (End): February 28, 2021
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Norberto Cysne Coimbra
Grantee:Priscila de Medeiros
Home 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)

Scientific publications (4)
(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)
P. MEDEIROS; I.R. DOS SANTOS; A.C. MEDEIROS; J.A. DA SILVA; S.H. FERREIRA; R.L. DE FREITAS; N.C. COIMBRA. Indomethacin attenuates mechanical allodynia during the organization but not the maintenance of the peripheral neuropathic pain induced by nervus ischiadicus chronic constriction injury. Brazilian Journal of Medical and Biological Research, v. 53, n. 5, p. -, 2020. Web of Science Citations: 0.
CALVO, FABRICIO; ALMADA, RAFAEL CARVALHO; DA SILVA, JULIANA ALMEIDA; MEDEIROS, PRISCILA; SOARES, JR., RAIMUNDO DA SILVA; DE PAIVA, YARA BEZERRA; RONCON, CAMILA MARRONI; COIMBRA, NORBERTO CYSNE. The Blockade of mu(1)- and kappa-Opioid Receptors in the Inferior Colliculus Decreases the Expression of Panic Attack-Like Behaviours Induced by Chemical Stimulation of the Dorsal Midbrain. NEUROPSYCHOBIOLOGY, v. 78, n. 4, p. 218-228, NOV 2019. Web of Science Citations: 0.
MEDEIROS, PRISCILA; NEGRINI-FERRARI, SYLMARA ESTHER; PALAZZO, ENZA; MAIONE, SABATINO; FERREIRA, SERGIO HENRIQUE; DE FREITAS, RENATO LEONARDO; COIMBRA, NORBERTO CYSNE. N-methyl-d-aspartate Receptors in the Prelimbic Cortex are Critical for the Maintenance of Neuropathic Pain. Neurochemical Research, v. 44, n. 9, p. 2068-2080, SEP 2019. Web of Science Citations: 2.
CALVO, FABRICIO; ALMADA, RAFAEL CARVALHO; DOS ANJOS-GARCIA, TAYLLON; FALCONI-SOBRINHO, LUIZ LUCIANO; PASCHOALIN-MAURIN, TATIANA; BAZAGLIA-DE-SOUSA, GUILHERME; MEDEIROS, PRISCILA; DA SILVA, JULIANA ALMEIDA; LOBAO-SOARES, BRUNO; COIMBRA, NORBERTO CYSNE. Panicolytic-like effect of mu(1)-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers. JOURNAL OF PSYCHOPHARMACOLOGY, v. 33, n. 5, p. 577-588, MAY 2019. Web of Science Citations: 2.

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