Anandamide Effects in a Streptozotocin-Induced Alzheimer's Disease-Like Sporadic Dementia in Rats

Autor(es)

Moreira-Silva, Daniel ^[1] ; Carrettiero, Daniel C. ^[2] ; Oliveira, Adriele S. A. ^[2] ; Rodrigues, Samanta ^[1] ; dos Santos-Lopes, Joyce ^[1] ; Canas, Paula M. ^[3] ; Cunha, Rodrigo A. ^{[3, 4]} ; Almeida, Maria C. ^[2] ; Ferreira, Tatiana L. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed ABC, Ctr Math Comp & Cognit, Sao Bernardo Do Campo - Brazil

^[2] Univ Fed ABC, Ctr Nat & Human Sci, Sao Bernardo Do Campo - Brazil

^[3] Univ Coimbra, Ctr Neurosci & Cell Biol CNC, Coimbra - Portugal

^[4] Univ Coimbra, Fac Med, Coimbra - Portugal

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN NEUROSCIENCE; v. 12, SEP 21 2018.
• Citações Web of Science: 2

Resumo

Alzheimer's disease (AD) is characterized by multiple cognitive deficits including memory and sensorimotor gating impairments as a result of neuronal and synaptic loss. The endocannabinoid system plays an important role in these deficits but little is known about its influence on the molecular mechanism regarding phosphorylated tau (p-tau) protein accumulation - one of the hallmarks of AD -, and on the density of synaptic proteins. Thus, the aim of this study was to investigate the preventive effects of anandamide (N-arachidonoylethanolamine, AEA) on multiple cognitive deficits and on the levels of synaptic proteins (syntaxin 1, synaptophysin and synaptosomal-associated protein, SNAP-25), cannabinoid receptor type 1 (CB1) and molecules related to p-tau degradation machinery (heat shock protein 70, HSP70), and Bcl2-associated athanogene (BAG2) in an AD-like sporadic dementia model in rats using intracerebroventricular (icv) injection of streptozotocin (STZ). Our hypothesis is that AEA could interact with HSP70, modulating the level of p-tau and synaptic proteins, preventing STZ-induced cognitive impairments. Thirty days after receiving bilateral icy injections of AEA or STZ or both, the cognitive performance of adult male Wistar rats was evaluated in the object recognition test, by the escape latency in the elevated plus maze (EPM), by the tone and context fear conditioning as well as in prepulse inhibition tests. Subsequently, the animals were euthanized and their brains were removed for histological analysis or for protein quantification by Western Blotting. The behavioral results showed that STZ impaired recognition, plus maze and tone fear memories but did not affect contextual fear memory and prepulse inhibition. Moreover, AEA prevented recognition and non-associative emotional memory impairments induced by STZ, but did not influence tone fear conditioning. STZ increased the brain ventricular area and this enlargement was prevented by AEA. Additionally, STZ reduced the levels of p-tau (Ser199/202) and increased p-tau (Ser396), although AEA did not affect these alterations. HSP70 was found diminished only by STZ, while BAG2 levels were decreased by STZ and AEA. Synaptophysin, syntaxin and CB1 receptor levels were reduced by STZ, but only syntaxin was recovered by AEA. Altogether, albeit AEA failed to modify some AD-like neurochemical alterations, it partially prevented STZinduced cognitive impairments, changes in synaptic markers and ventricle enlargement. This study showed, for the first time, that the administration of an endocannabinoid can prevent AD-like effects induced by STZ, boosting further investigations about the modulation of endocannabinoid levels as a therapeutic approach for AD. (AU)

• Processo FAPESP: 16/24773-7 - Possível efeito preventivo da anandamida sobre as alterações de neuroplasticidade e modulação do sistema endocanabinoide induzidas pela estreptozotocina
• Beneficiário: Daniel Moreira Silva
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 15/02991-0 - Envolvimento dos canais TRPM8 na termorregulação de ratos Wistar
• Beneficiário: Maria Camila Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/14661-1 - Papel do sistema canabinoide sobre a atividade de tau e sua relação com o desempenho cognitivo em modelo de Doença de Alzheimer esporádica em ratos
• Beneficiário: Daniel Moreira Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/23426-9 - Beta amiloide na patologia de Alzheimer: morte ou sobrevivência? Envolvimento da via NF-kappaB e BAG2
• Beneficiário: Daniel Carneiro Carrettiero
• Modalidade de apoio: Auxílio à Pesquisa - Regular