Systemic inflammation mediated by sepsis promotes Alzheimer's Disease pathology in animal models

• Grant number: 21/06496-4
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 28, 2022
• End date: February 27, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria José Alves da Rocha
• Grantee: Carlos Henrique Rocha Catalão
• Supervisor: Tatiana Barichello
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Texas Health Science Center at Houston (UTHealth), United States
• Associated to the scholarship: 17/12462-0 - Study of the neuroprotective effect of simvastatin on cognitive impairments in sepsis surviving animals, BP.PD

Abstract

Worldwide, more than 30 million people are affected by sepsis, which is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Several studies suggest that sepsis might act as a significant inflammatory "hit" that potentially increases the susceptibility of the brain to neurodegenerative disease and the development of dementia later in life. Survivors of sepsis are now thought to persistently have high circulating concentrations of proinflammatory mediators after hospital discharge. In that sense, these subjects could also present persistent neuroinflammation, the event that is a common feature preceding the clinical onset of several neurodegenerative diseases, such as Alzheimer's disease (AD). AD is pathologically associated with the accumulation of misfolded amyloid-² (A²) and hyperphosphorylated tau proteins in the brain. The association between AD pathology and bacterial/viral infection is supported by compelling evidence that demonstrates that the presence of microorganisms in the brain increases A² production, facilitating the misfolding and deposition of this protein and triggering pathological cascades. Also, peripheral inflammation is a known risk factor associated with AD and a common outcome in several types of infection. Systemic inflammation triggered by sepsis compromises blood-brain barrier (BBB) permeability, allowing the infiltration of peripheral immune cells into the central nervous system (CNS). These events trigger the activation of glial cells, causing neuronal loss and brain dysfunction. In that sense, both brain and peripheral infections are events that may be putative AD risk factors. In this work, we will assess the contribution of peripheral microbial infection induced by sepsis in AD pathology. (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)

BARICHELLO, TATIANA; GIRIDHARAN, VIJAYASREE V.; CATALAO, CARLOS HENRIQUE R.; RITTER, CRISTIANE; DAL-PIZZOL, FELIPE. Neurochemical effects of sepsis on the brain. Clinical Science, v. 137, n. 6, p. 14-pg., 2023-03-01. (21/06496-4)

GIRIDHARAN, VIJAYASREE V.; CATUMBELA, CELSO S. G.; CATALAO, CARLOS HENRIQUE R.; LEE, JUNEYOUNG; GANESH, BHANU P.; PETRONILHO, FABRICIA; DAL-PIZZOL, FELIPE; MORALES, RODRIGO; BARICHELLO, TATIANA. Sepsis exacerbates Alzheimer's disease pathophysiology, modulates the gut microbiome, increases neuroinflammation and amyloid burden. MOLECULAR PSYCHIATRY, v. N/A, p. 11-pg., 2023-07-14. (21/06496-4)

BARICHELLO, TATIANA; CATALAO, CARLOS HENRIQUE ROCHA; ROHLWINK, URSULA K.; VAN DER KUIP, MARTIJN; ZAHARIE, DAN; SOLOMONS, REGAN S.; VAN TOORN, RONALD; VAN FURTH, MARCELINE TUTU; HASBUN, RODRIGO; IOVINO, FEDERICO; et al. Bacterial meningitis in Africa. FRONTIERS IN NEUROLOGY, v. 14, p. 18-pg., 2023-02-14. (21/06496-4)