Lactose intolerance: relationship with psychiatric disorders and neurobiological and reproductive and enteric pathophysiological characterizations

• Grant number: 24/05651-4
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Thiago Berti Kirsten
• Grantee: Thiago Berti Kirsten
• Host Institution: Vice-Reitoria de Pesquisa e Pós-Graduação. Universidade Paulista (UNIP). São Paulo , SP, Brazil

Abstract

Lactose intolerance presents high incidence, with symptoms such as diarrhea and abdominal pain. The mechanisms have not yet been elucidated and there are few and limited experimental models. Women are more reported and correlations with psychiatric disorders and reproductive impairments have been described. The objective of this project is to propose and study experimental models of lactose intolerance in rats, studying the manifestation of clinical signs, their pathophysiological and neurobiological bases, and possible relationships with psychiatric disorders, reproduction, and sexual dimorphism. It is intended to: propose and apply two experimental models of lactose intolerance; evaluate the manifestation of characteristics related to lactose intolerance (monitoring clinical signs); evaluate behavioral tests related to psychiatric disorders (anxiety, socialization, and depression); evaluate central and peripheral pathways (monoamine-related biomarkers); evaluate enteric and reproductive organs pathophysiological bases; evaluate the gene and epigenetic expression of hypothalamic-pituitary-gonadal (HHG) axis biomarkers; and evaluate hormonal levels. Solutions with different concentrations of lactose will be prepared to define the best dose. Male and female Wistar rats will be induced to symptoms of lactose intolerance with the provision of diets rich in lactose (lactose solution and commercial formula for 14 days). It will be evaluated: stool consistency, body weight, diet consumption, behaviors (light-dark box, social preference, and forced swimming tests), enteric, uterine, and ovarian tissues morphology (histopathology and morphometry), brain levels of dopamine, genetic and epigenetic expressions of the enzyme tryptophan hydroxylase 1 in the intestine and of HHG axis biomarkers, and serum levels of serotonin and of HHG axis hormones. (AU)