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Possible preventive effect of anandamide on alterations of neuroplasticity and modulation of endocannabinoid system induced by streptozotocin

Grant number: 16/24773-7
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): April 05, 2017
Effective date (End): February 04, 2018
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Tatiana Lima Ferreira
Grantee:Daniel Moreira Silva
Supervisor abroad: Attila Kofalvi
Home Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
Local de pesquisa : Universidade de Coimbra (UC), Portugal  
Associated to the scholarship:14/14661-1 - Role of cannabinoid system on tau activity and its relation to the cognitive performance in a model of sporadic Alzheimer's Disease in rats, BP.DR

Abstract

Alzheimer's disease (AD) is characterized by the gradual and continuous increase of multiple cognitive deficits. Cognitive alterations are correlated with reduction of volume and/or synaptic plasticity in regions such as hippocampus and neocortex. Recent studies indicate a great influence of the endocannabinoid system on AD progress, regulating mechanisms of neuroplasticity and cognitive processes. Reduced levels of endocannabinoids such as anandamide (ANA) are observed during the course of AD, and there is a correlation with cognitive deficits and an increase in the density of CB1 receptors in the neocortex, which could act as a compensation for the system.Most AD studies use transgenic animals, with more relation to familial and not sporadic AD, which is multifactorial and corresponds to 95% of the cases. The data obtained from the project developed in Brazil show recognition and emotional memory deficits in sporadic AD and ANA preventive effect on recognition memory impairment. Thus, the aim of the present study is to investigate the synaptic loss and changes in the endocannabinoid system in the sporadic AD model. In addition, to verify if ANA could interfere in these expected changes, aiming to understand the molecular mechanisms underlying the cognitive alterations observed. This objective was foreseen in the Brazil's project work plan and its accomplishment would be essential to complement the already completed molecular analyzes of levels of phosphorylated tau protein and chaperones involved in its degradation.For this, Wistar rats will receive intracerebroventricularly streptozotocin (to induce the pathophysiological aspects of sporadic AD), preceded by the administration of ANA using the same pathway. Afterwards, animals will be submitted to the cognitive test and will have their brains removed for Western Blotting analysis (levels of CB1, CB2 and synaptophysin receptors) and ANA hydrolysis. (AU)

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)
MOREIRA-SILVA, DANIEL; VIZIN, ROBSON C. L.; MARTINS, TALITA M. S.; FERREIRA, TATIANA L.; ALMEIDA, MARIA C.; CARRETTIERO, DANIEL C. Intracerebral Injection of Streptozotocin to Model Alzheimer Disease in Rats. BIO-PROTOCOL, v. 9, n. 20 OCT 20 2019. Web of Science Citations: 0.
MOREIRA-SILVA, DANIEL; CARRETTIERO, DANIEL C.; OLIVEIRA, ADRIELE S. A.; RODRIGUES, SAMANTA; DOS SANTOS-LOPES, JOYCE; CANAS, PAULA M.; CUNHA, RODRIGO A.; ALMEIDA, MARIA C.; FERREIRA, TATIANA L. Anandamide Effects in a Streptozotocin-Induced Alzheimer's Disease-Like Sporadic Dementia in Rats. FRONTIERS IN NEUROSCIENCE, v. 12, SEP 21 2018. Web of Science Citations: 1.

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