COGNITIVE EVALUATION IN RATES WITH APICAL PERIODONTITIS TREATED WITH MELATONIN

• Grant number: 24/07729-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Endodontics
• Principal Investigator: Doris Hissako Matsushita
• Grantee: Anna Clara Cachoni
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Associated scholarship(s): 25/08439-9 - Effects of melatonin on the activation and inflammation of astrocytes in the central nervous system: an ex vivo study on primary cell cultures, BE.EP.MS

Abstract

Currently, it is well established in the literature that chronic inflammations in the teeth such as Apical Periodontitis (AP) and Periodontal Disease (PD) can cause systemic disorders. AP is an inflammation at the apex of the dental root, generally caused by infection by bacteria originating from the root canal system. The inflammatory response generated by this infection promotes an increase in pro-inflammatory cytokines that can spread systemically. Furthermore, these cytokines are related to the increased expression of TAU and beta-amyloid proteins, which are involved in the development of cognitive alterations present in neurodegenerative pathologies such as dementia. Due to all these factors, there is a correlation between inflammation and Alzheimer's. However, the literature is scarce in relation to studies that relate BP to systemic cognitive changes. In addition, studies demonstrate that melatonin (MEL) has anti-inflammatory and antioxidant effects and can reverse systemic changes induced by PD and AP. Furthermore, scientific evidence shows the strong effectiveness of MEL in inhibiting the hyperphosphorylation of the TAU protein. In view of this, the objectives of the present study will be to investigate whether young rats will suffer cognitive changes after 90 days AP induction and whether treatment with MEL can prevent the progression of the infection. To this end, 52 Wistar rats (2 months old) will be distributed into 4 groups: 1) control rats (CN); 2) control rats treated with MEL (CNMEL); 3) rats with 4 PAs induced in the 1st and 2nd upper and lower molars on the right side (PA); 4) male rats with 4 APs treated with MEL (PAMEL). AP will be induced by exposing the pulp tissue to the oral environment, using a carbon steel drill equipped with a 0.1mm ball at the end. On the 1st day of experiments, behavioral tests will begin (memory test, open field and plus maze) on these animals to begin the cognitive assessment. After 30 days of induction of oral inflammation (AP), treatment with MEL (0.5 mg/kg, orally via gavage) will be initiated for 60 days. After the MEL treatment period, behavioral tests will be performed again in all experimental groups (CN, CNMEL, PA and PAMEL). 24 hours after carrying out the last behavioral test, euthanasia will begin and the following experiments will be carried out: 1) histological analysis of the hippocampus; 2) evaluation of TAU and amyloid ² proteins in the hippocampus using the western blotting technique; 3) analysis of TNF-± content in the hippocampus; 4) evaluation of the plasma concentration of inflammatory cytokines (TNF-± and IL-6). Statistical analyzes will be performed using two or three factor analysis of variance followed by the Bonferroni test (p<0.005).