title: Hidden prenatal malnutrition in the rat: role of β₁-adrenoceptors on synaptic plasticity in the frontal cortex.
abstract: Moderate reduction in the protein content of the mother's diet (hidden malnutrition) does not alter body and brain weights of rat pups at birth, but leads to dysfunction of neocortical noradrenaline systems together with impaired long-term potentiation and visuo-spatial memory performance. As β₁-adrenoceptors and downstream protein kinase signaling are critically involved in synaptic long-term potentiation and memory formation, we evaluated the β₁-adrenoceptor density and the expression of cyclic-AMP dependent protein kinase, calcium/calmodulin-dependent protein kinase and protein kinase Fyn, in the frontal cortex of prenatally malnourished adult rats. In addition, we also studied if β₁-adrenoceptor activation with the selective β₁ agonist dobutamine could improve deficits of prefrontal cortex long-term potentiation presenting these animals. Prenatally malnourished rats exhibited half of β₁-adrenoceptor binding, together with a 51% and 65% reduction of cyclic AMP-dependent protein kinase α and calcium/calmodulin-dependent protein kinase α expression, respectively, as compared with eutrophic animals. Administration of the selective β₁ agonist dobutamine prior to tetanization completely rescued the ability of the prefrontal cortex to develop and maintain long-term potentiation in the malnourished rats. Results suggest that under-expression of neocortical β₁-adrenoceptors and protein kinase signaling in hidden malnourished rats functionally affects the synaptic networks subserving prefrontal cortex long-term potentiation. β₁-adrenoceptor activation was sufficient to fully recover neocortical plasticity in the PKA- and calcium/calmodulin-dependent protein kinase II-deficient undernourished rats, possibly by producing extra amounts of cAMP and/or by recruiting alternative signaling cascades.
authors.affiliation: Unit of Nutritional Neuroscience, Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Chile School of Psychology, Autonomous University of Chile, Santiago, Chile.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Flores
authors.forename: Hernán
authors.initials: H
authors.lastname: Pérez
authors.forename: Luis
authors.initials: L
authors.lastname: Valladares
authors.forename: Carlos
authors.initials: C
authors.lastname: Morgan
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Gatica
authors.forename: Héctor
authors.initials: H
authors.lastname: Burgos
authors.forename: Ricardo
authors.initials: R
authors.lastname: Olivares
authors.forename: Alejandro
authors.initials: A
authors.lastname: Hernández
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004032:Diet; D004280:Dobutamine / Q000494:pharmacology; D055724:Electrophysiological Phenomena; D005260:Female; D048070:Fetal Nutrition Disorders / Q000503:physiopathology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008566:Membranes / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects*; D009929:Organ Size / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D018342:Receptors, Adrenergic, beta-1; D004280:Dobutamine; C490511:Frk protein, rat; D019061:src-Family Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2