Folate administration ameliorates neurobehavioral effects of third trimester-equivalent ethanol exposure

LEONARDO MARENGO; AGOSTINA BAREY; AGUSTÍN SALGUERO; FABIO M.C.; D'ADDARIO, CLAUDIO; PAUTASSI R.M.

Montevideo

Congreso; 2das Jornadas de Investigación en consumo de sustancias en Uruguay; 2023

Universidad de la República (Montevideo, Uruguay)

FOLATE ADMINISTRATION AMELIORATES NEUROBEHAVIORAL EFFECTS OF THIRD TRIMESTER-EQUIVALENT ETHANOL EXPOSUREMarengo, Leonardoa,*; Barey, Agostinaa; Salguero, Agustína; Fabio, María Carolinaa,b; D?Addario, Claudioc, Pautassi, Ricardo Marcosa,baInstituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET-UNC), Córdoba, Argentina.bFacultad de Psicología, Universidad Nacional de Córdoba, Argentina.cUniversidad de Téramo, Departamento de Biociencia y Tecnología Agroalimentaria y Ambiental*Corresponding author: Leonardo Marengo, Instituto de Investigación Médica M. y M. Ferreyra (INIMEC-CONICET-UNC), Friuli 2434, Barrio Colinas de Vélez Sarsfield, Córdoba, CP 5016. Email: lmarengo@immf.uncor.eduIntroduction: Prenatal ethanol (alcohol) exposure (PEE) is one of the main preventable causes of developmental disabilities worldwide. PEE exerts a myriad of physical malformations and cognitive impairments in the exposed fetus. The third trimester ?brain growth spurt? equivalent (i.e., PDs 4?9) is characterized by neuronal maturation, including axonal growth, dendritic arborization, among others relevant neural processes. Importantly, this is an ontogenetic period particularly sensitive to ethanol insults. Currently, there are pharmacological and environmental treatments to reverse the deleterious effects of PEE, but more recently, nutritional supplements like folate (i.e., B9 vitamin) have gained more attention. Objective: In this study, we examined whether folate administration during this ontogenetic period reverses neurobehavioral effects associated with ethanol exposure. Methods: between PDs 4-9 male and female Wistar rats were administered with folate (20 mg/kg, i.g) or vehicle (tap water, i.g.). 2 hours apart the rats were exposed to ethanol (2.5 g/kg i.g. at 0 and 2 h, total dose: 5.00 g/kg) or to sham intubations. At PD 10, pups received only a folate ?booster? or vehicle. At PDs 15-18, rats were evaluated in validated behavioral tests that measure anxiety-like and exploratory and risk-taking behaviors. At PDs 23-26, rats were evaluated in the sucrose preference test (two sessions, 2% sucrose). Results: We found significant differences (and a possible protective effect of folate) between the groups treated with folate and ethanol in the behavioral tests conducted. Significant differences between sessions in the sucrose preference test was observed in animals treated with ethanol, an effect reversed by animals that received folate. Discussion: Folate could possibly be an economically viable alternative, easily administered in rats to reduce numerous neurobehavioral effects associated with ethanol exposure during the third gestational trimester.Keywords: folate, ethanol, third trimester, brain growth spurt, rats