Hidden prenatal malnutrition in the rat: role of β1‐adrenoceptors on synaptic plasticity in the frontal cortex

• Published in: Journal of neurochemistry 2011-10, Vol.119 (2), p.314-323
• Main Authors: Flores, Osvaldo, Pérez, Hernán, Valladares, Luis, Morgan, Carlos, Gatica, Arnaldo, Burgos, Héctor, Olivares, Ricardo, Hernández, Alejandro
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Agonists - pharmacology; Animals; Biological and medical sciences; Body Weight - physiology; Brain - drug effects; Brain - embryology; Brain - growth & development; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; CaMKII; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cyclic AMP-Dependent Protein Kinases - metabolism; Diet; Dobutamine - pharmacology; Electrophysiological Phenomena; Female; Fetal Nutrition Disorders - physiopathology; frontal cortex; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Long-Term Potentiation - drug effects; long‐term potentiation; Male; Medical sciences; Membranes - metabolism; Metabolic diseases; Neuronal Plasticity - drug effects; Organ Size - physiology; Other nutritional diseases (malnutrition, nutritional and vitamin deficiencies...); PKA; Prefrontal Cortex - drug effects; Pregnancy; prenatal malnutrition; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta-1 - drug effects; Receptors, Adrenergic, beta-1 - metabolism; Receptors, Adrenergic, beta-1 - physiology; src-Family Kinases - metabolism; Vertebrates: nervous system and sense organs; β1‐adrenoceptor
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2011.07429.x

J. Neurochem. (2011) 119, 314–323. 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.