Endocannabidiome as a tool to determine biomarkers candidates of the gut-brain-axis development during the first 1,000 days of life

• Grant number: 23/04619-7
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2023
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Alline Cristina de Campos
• Grantee: Alline Cristina de Campos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto
• Associated researchers: André Carlos Ponce de Leon Ferreira de Carvalho ; André Fujita ; Carla Romano Taddei ; Patricia Cristina Baleeiro Beltrão Braga ; Tamires Amabile Valim Brigante
• Associated scholarship(s): 25/13091-1 - Molecular and bioinformatics analyses of lipidomics-related data in the Laboratory of Pharmacology of Neuroplasticity and Cannabinoid Research Center, BP.TT; 24/17131-5 - Molecular and bioinformatics analyses of lipidomics-related data in the Laboratory of Pharmacology of Neuroplasticity and Cannabinoid Research Center, BP.TT

Abstract

The first one thousand days of life are essential and, at the same time, a critical and vulnerable period for brain development. During the embryonic period, our central nervous system, neurons, microglia and astrocytes are formed and given their specific (but still basic) designations related to location (anatomical and histological), neurotransmitters (release and expressed receptors) etc. Neurodevelopment is not interrupted after birth, this being the moment when the processes of myelination and organization of synaptic contacts and metabolic processes, orchestrated mainly by astrocytes, begin to take shape. During the first years of life, our newly formed brain is extremely plastic and, during this period, its cellular components "learn" how to connect, how to communicate and specialize to perform functions, mainly executive calls. However, it is also during this period that other peripheral systems of our body begin processes aimed at gaining function and maturation. A process that seems to follow, in a way, the rhythm of formation and maturation, in complexity, of our central nervous system is the intestinal microbiota. In addition, it is known that the microbiota has a connection with the central nervous system through the brain-gut-microbiota axis, which coincidentally seems to develop during the first years of life, a fact that remains little known (mainly in the clinical/human context). Thus, in the present project, we will investigate possible neuromodulators involved in the brain-gut-microbiota communication during the first thousand days of life of babies born in the city of São Paulo and from different socioeconomic levels. In this context, knowing that: 1- endocannabinoids of lipid origin are involved in processes of division, migration and maturation of the central nervous system during neurodevelopment, controlling several behavioral functions and stress resilience; 2- That the hydrolysis of these compounds can give rise to a group of n-acyl neurotransmitters and fatty acids; 3- that in addition to being expressed in the brain, endocannabinoids also control peripheral systems such as the gut and the immune system; Therefore, the present proposal aim to test the hypothesis that endocannabinoids and n-acyl neurotransmitters are the link between neurodevelopment and the brain-gut-microbiota axis during the first 1,000 days of life .(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)

FATORI, DANIEL; SHEPHARD, ELIZABETH; BENETTE, DANILO; NASPOLINI, NATHALIA FERRAZZO; GUZMAN, GROVER CASTRO; WANG, JAQUELINE YU TING; TOTOLO, PEDRO; MAFRA, ANTHONIETA LOOMAN; ISAIAS, CAIO; DOS SANTOS, DAVI PEREIRA; et al. Identifying biomarkers and trajectories of executive functions and language development in the first 3 years of life: Design, methods, and findings of the Germina cohort study. DEVELOPMENT AND PSYCHOPATHOLOGY, v. N/A, p. 11-pg., 2025-03-05. (20/05964-1, 23/04619-7)