title: Caffeine exposure during rat brain development causes memory impairment in a sex selective manner that is offset by caffeine consumption throughout life.
abstract: Caffeine is the psychostimulant most consumed worldwide. In moderate doses, it affords a beneficial effect in adults and upon aging, but has a deleterious effect during brain development. We now tested if caffeine consumption by rats (0.1, 0.3, 1.0 g/L in the drinking water, only during active cycle and weekdays) during adulthood could revert the potentially negative effects of caffeine during early life. Thus, we compared caffeine intake starting 15 days before mating and lasting either up to weaning (development) or up to adulthood, on behavior and synaptic proteins in male and female rats. Recognition memory was impaired only in female rats receiving caffeine (0.3 and 1.0 g/L) during development, coincident with increased proBDNF and unchanged BDNF levels in the hippocampus. Caffeine in both treatment regimens caused hyperlocomotion only in male rats, whereas anxiety-related behavior was attenuated in both sexes by caffeine (1.0 g/L) throughout life. Both caffeine treatment regimens decreased GFAP (as an astrocyte marker) and SNAP-25 (as a nerve terminals marker) in the hippocampus from male rats. TrkB receptor was decreased in the hippocampus from both sexes and treatment regimens. These findings revealed that caffeine intake during a specific time window of brain development promotes sex-dependent behavioral outcomes related to modification in BDNF signaling. Furthermore, caffeine throughout life can overcome the deleterious effects of caffeine on recognition memory during brain development in female rats.
authors.affiliation: Laboratório de Estudos sobre o Sistema Purinérgico, Universidade Federal Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ardais
authors.affiliation: Laboratório de Estudos sobre o Sistema Purinérgico, Universidade Federal Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Andréia S
authors.initials: AS
authors.lastname: Rocha
authors.affiliation: Laboratório de Estudos sobre o Sistema Purinérgico, Universidade Federal Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Maurício Felisberto
authors.initials: MF
authors.lastname: Borges
authors.affiliation: Laboratório de Estudos sobre o Sistema Purinérgico, Universidade Federal Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Gabriela T
authors.initials: GT
authors.lastname: Fioreze
authors.affiliation: Laboratório de Estudos sobre o Sistema Purinérgico, Universidade Federal Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Cássia
authors.initials: C
authors.lastname: Sallaberry
authors.affiliation: Laboratório de Estudos sobre o Sistema Purinérgico, Universidade Federal Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Mioranzza
authors.affiliation: Laboratório de Estudos sobre o Sistema Purinérgico, Universidade Federal Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Nunes
authors.affiliation: Laboratório de Estudos sobre o Sistema Purinérgico, Universidade Federal Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Natália
authors.initials: N
authors.lastname: Pagnussat
authors.affiliation: Laboratório de Estudos sobre o Sistema Purinérgico, Universidade Federal Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Paulo Henrique S
authors.initials: PH
authors.lastname: Botton
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Cunha
authors.affiliation: Laboratório de Estudos sobre o Sistema Purinérgico, Universidade Federal Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, 90035-003 Porto Alegre, RS, Brazil. Electronic address: loporciuncula@yahoo.com.
authors.forename: Lisiane de Oliveira
authors.initials: Lde O
authors.lastname: Porciúncula
mesh_terms: D000818:Animals; D001007:Anxiety; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002110:Caffeine / Q000008:administration & dosage* / Q000009:adverse effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D005904:Glial Fibrillary Acidic Protein; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D002110:Caffeine
keywords: BDNF; Brain development; Caffeine; Memory; Psychostimulant; Sex differences