title: β2-adrenoceptor stimulation restores frontal cortex plasticity and improves visuospatial performance in hidden-prenatally-malnourished young-adult rats.
abstract: Moderate reduction in dietary protein composition of pregnant rats from 25% to 8% casein, calorically compensated by carbohydrates, has been described as a "hidden malnutrition" because it does not alter body and brain weights of pups at birth. However, this dietary treatment leads to altered central noradrenergic systems, impaired cortical long-term potentiation (LTP) and worsened visuo-spatial memory performance. Given the increasing interest on the role played by β2-adrenoceptors (β2-ARs) on brain plasticity, the present study aimed to address the following in hidden-malnourished and eutrophic control rats: (i) the expression levels of β2-ARs in the frontal cortex determined by immunohistochemistry, and (ii) the effect of the β2 selective agonist clenbuterol on both LTP elicited in vivo in the prefrontal cortex and visuospatial performance measured in an eight-arm radial maze. Our results showed that, prenatally malnourished rats exhibited a significant reduction of neocortical β2-AR expression in adulthood. Concomitantly, they were unable to elicit and maintain prefrontal cortex LTP and exhibited lower visuospatial learning performance. Administration of clenbuterol (0.019, 0.038 and 0.075 mg/kg i.p.) enhanced LTP in malnourished and control animals and restored visuospatial learning performance in malnourished but not in normal rats, in a dose-dependent manner. The results suggest that decreased density of neocortical β2-ARs during postnatal life, subsequent to hidden prenatal malnutrition might affect some synaptic networks required to elicit neocortical LTP and form visuospatial memory, since those neuroplastic deficits were counteracted by β2-AR stimulation.
authors.affiliation: Faculty of Medicine, University of Santiago de Chile, Santiago, Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Sáez-Briones
authors.affiliation: Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile.
authors.forename: Rubén
authors.initials: R
authors.lastname: Soto-Moyano
authors.affiliation: School of Psychology, Central University of Chile, Santiago, Chile; School of Psychology, University of Santiago de Chile, Santiago, Chile.
authors.forename: Héctor
authors.initials: H
authors.lastname: Burgos
authors.affiliation: School of Psychology, Autonomous University of Chile, Santiago, Chile; Doctoral Program in Psychology, Faculty of Social Sciences, University of Chile, Santiago, Chile.
authors.forename: Amparo
authors.initials: A
authors.lastname: Castillo
authors.affiliation: Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Valladares
authors.affiliation: Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile. Electronic address: cmorgan@inta.uchile.cl.
authors.forename: Carlos
authors.initials: C
authors.lastname: Morgan
authors.affiliation: Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile.
authors.forename: Hernán
authors.initials: H
authors.lastname: Pérez
authors.affiliation: Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile.
authors.forename: Rafael
authors.initials: R
authors.lastname: Barra
authors.affiliation: Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Constandil
authors.affiliation: Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Laurido
authors.affiliation: Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile. Electronic address: alejandro.hernandez@usach.cl.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Hernández
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage; D000818:Animals; D002976:Clenbuterol / Q000008:administration & dosage; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology*; D011502:Protein-Energy Malnutrition / Q000378:metabolism / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2; D002976:Clenbuterol
keywords: Clenbuterol; Long-term potentiation; Prefrontal cortex; Prenatal protein malnutrition; Visuospatial performance; β(2)-Adrenoceptor