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Perinatal asphyxia results in altered expression of the hippocampal acylethanolamide/endocannabinoid signaling system associated to memory impairments in postweaned rats.

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Date

2015-11-03

Authors

Blanco, Eduardo
Galeano, Pablo
Holubiec, Mariana I
Romero, Juan I
Logica, Tamara
Rivera, Patricia
Pavón, Francisco J
Suarez, Juan
Capani, Francisco
Rodríguez de Fonseca, Fernando

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Frontiers Media
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Abstract

Perinatal asphyxia (PA) is an obstetric complication that strongly affects the CNS. The endocannabinoid system (ECS) is a lipid transmitter system involved in several physiological processes including synaptic plasticity, neurogenesis, memory, and mood. Endocannabinoids, and other acylethanolamides (AEs) without endocannabinoid activity, have recently received growing attention due to their potential neuroprotective functions in neurological disorders, including cerebral ischemia. In the present study, we aimed to analyze the changes produced by PA in the major metabolic enzymes and receptors of the ECS/AEs in the hippocampus using a rodent model of PA. To induce PA, we removed uterine horns from ready-to-deliver rats and immersed them into a water bath during 19 min. Animals delivered spontaneously or by cesarean section were employed as controls. At 1 month of age, cognitive functions were assessed and immunohistochemical procedures were carried out to determine the expression of NeuN and glial fibrillary acidic protein, enzymes responsible for synthesis (DAGLα and NAPE-PLD) and degradation (FAAH) of ECS/AEs and their receptors (CB1 and PPARα) in the hippocampus. Postweaned asphyctic rats showed impaired recognition and spatial reference memory that were accompanied by hippocampal astrogliosis and changes in the expression of enzymes and receptors. The most remarkable findings in asphyctic rats were a decrease in the expression of NAPE-PLD and PPARα in both hippocampal areas CA1 and CA3. In addition, postweaned cesarean delivery rats showed an increase in the immunolabeling for FAAH in the hippocampal CA3 area. Since, NAPE-PLD and PPARα are proteins that participate in the biochemical process of AEs, specially the neuroprotective oleoylethanolamide, these results suggest that PA dysregulates this system. These data encourage conducting future studies using AEs as potential neuroprotective compounds in animal models of PA.

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Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Diseases::Wounds and Injuries::Asphyxia
Medical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Psychophysiology::Arousal::Attention
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Physical Therapy Modalities::Balneology::Baths
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes
Medical Subject Headings::Phenomena and Processes::Biological Phenomena::Biological Processes
Procesos biológicos
Medical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Brain Ischemia
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Obstetric Surgical Procedures::Delivery, Obstetric::Cesarean Section
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Glial Fibrillary Acidic Protein
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus
Medical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Memory
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Animal
Medical Subject Headings::Diseases::Nervous System Diseases
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Morphogenesis::Embryonic and Fetal Development::Organogenesis::Neurogenesis
Medical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal Plasticity
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Monounsaturated::Oleic Acids
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Peroxisome Proliferator-Activated Receptors::PPAR alpha
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes
Medical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats

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Keywords

Perinatal asphyxia, Hippocampus, Memory, DAGLα, NAPE-PLD, CB1, PPARα, FAAH, Animales, Asfixia, Atención, Baños, Procesos bioquímicos, Isquemia cerebral, Cesárea, Cognición, Endocannabinoides, Proteína ácida fibrilar de la glía, Memoria, Modelos animales, Enfermedades del sistema nervioso, Neurogénesis, Plasticidad neural, Ácidos oleicos, Embarazo, Procesos fisiológicos, Ratas

Citation

Blanco E, Galeano P, Holubiec MI, Romero JI, Logica T, Rivera P, et al. Perinatal asphyxia results in altered expression of the hippocampal acylethanolamide/endocannabinoid signaling system associated to memory impairments in postweaned rats. Front Neuroanat. 2015; 9:141