The anti-inflamamtory action of interleukin-10 in response to physical trainning reduces the Alzheimer's disease progression in an experimental model

Author(s)

Rafael dos Santos Brícola

• Document type: Master's Dissertation
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2022-12-08

Examining board members

Eduardo Rochete Ropelle; Bruno de Melo Carvalho; Igor Luchini Baptista

• Advisor: Eduardo Rochete Ropelle

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease that results in cognitive impairment of affected patients over time. The etiology of disease is multifactorial, with some well-established contributors, including increased gene expression of Amyloid precursor protein (app) and presenilin-1 (ps1), which directly contribute to the accumulation of beta amyloid proteins (?A). Beta-amyloid proteins are neurotoxic and accumulate chronologically and form senile plaques in neural tissue. It is postulated that chronic inflammation may contribute to the accumulation of beta-amyloid and the formation of senile plaques in the hippocampus and cortex over time. On the other hand, studies have shown that physical exercise is able to improve synaptic responses in the hippocampus, reducing inflammatory markers, ?A accumulation and the formation of senile plaques and improving cognitive responses. Here, in silico analysis, we observed that humans with AD have high levels of inflammatory markers in the hippocampus and we report that aerobic physical training promoted a potent anti-inflammatory response, reduced microglial activation and the deposition of beta amyloid proteins in the hippocampus of mice APPswe/PS1?E9 (APP/PS1+) and prevented cognitive decline in the mouse model of AD. We also observed that wild type and APP/PS1+ mice have high expression of IL10 in the hippocampal tissue after a physical exercise session. Furthermore, intranasal treatment with recombinant IL10 (IL10r) in wild-type mice was able to activate the pSTAT3 signaling pathway. Added to this, APP/PS1+ mice that received intranasal rIL10 showed cognitive improvement. Thus, we conclude that the anti-inflammatory activity of IL10 is linked to the cognitive benefits promoted by physical training in individuals predisposed to Alzheimer's disease (AU)

• FAPESP's process: 20/03142-4 - Effect of physical exercise on UPRmt, mitochondrial function and beta-amyloid accumulation in the hippocampus of APOE mice - /-
• Grantee: Rafael dos Santos Brícola
• Support Opportunities: Scholarships in Brazil - Master