title: Effect of perinatal asphyxia on tuberomammillary nucleus neuronal density and object recognition memory: A possible role for histamine?
abstract: Perinatal asphyxia (PA) is associated with long-term neuronal damage and cognitive deficits in adulthood, such as learning and memory disabilities. After PA, specific brain regions are compromised, including neocortex, hippocampus, basal ganglia, and ascending neuromodulatory pathways, such as dopamine system, explaining some of the cognitive disabilities. We hypothesize that other neuromodulatory systems, such as histamine system from the tuberomammillary nucleus (TMN), which widely project to telencephalon, shown to be relevant for learning and memory, may be compromised by PA. We investigated here the effect of PA on (i) Density and neuronal activity of TMN neurons by double immunoreactivity for adenosine deaminase (ADA) and c-Fos, as marker for histaminergic neurons and neuronal activity respectively. (ii) Expression of the histamine-synthesizing enzyme, histidine decarboxylase (HDC) by western blot and (iii) thioperamide an H3 histamine receptor antagonist, on an object recognition memory task. Asphyxia-exposed rats showed a decrease of ADA density and c-Fos activity in TMN, and decrease of HDC expression in hypothalamus. Asphyxia-exposed rats also showed a low performance in object recognition memory compared to caesarean-delivered controls, which was reverted in a dose-dependent manner by the H3 antagonist thioperamide (5-10mg/kg, i.p.). The present results show that the histaminergic neuronal system of the TMN is involved in the long-term effects induced by PA, affecting learning and memory.
authors.affiliation: Program of Physiology & Biophysics, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Flores-Balter
authors.affiliation: Program of Physiology & Biophysics, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.
authors.forename: Héctor
authors.initials: H
authors.lastname: Cordova-Jadue
authors.affiliation: Program of Physiology & Biophysics, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Chiti-Morales
authors.affiliation: Program of Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.
authors.forename: Carolyne
authors.initials: C
authors.lastname: Lespay
authors.affiliation: Program of Physiology & Biophysics, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile; Program of Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Espina-Marchant
authors.affiliation: Program of Physiology & Biophysics, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile; Biomedical Neuroscience Institute, BNI, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.
authors.forename: Romina
authors.initials: R
authors.lastname: Falcon
authors.affiliation: Program of Physiology & Biophysics, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile; Biomedical Neuroscience Institute, BNI, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.
authors.forename: Noemi
authors.initials: N
authors.lastname: Grinspun
authors.affiliation: Program of Physiology & Biophysics, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile; Biomedical Neuroscience Institute, BNI, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.
authors.forename: Jessica
authors.initials: J
authors.lastname: Sanchez
authors.affiliation: Program of Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.
authors.forename: Diego
authors.initials: D
authors.lastname: Bustamante
authors.affiliation: Program of Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile.
authors.forename: Paola
authors.initials: P
authors.lastname: Morales
authors.affiliation: Program of Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile; Biomedical Neuroscience Institute, BNI, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. Electronic address: mh-marschitz@med.uchile.cl.
authors.forename: Mario
authors.initials: M
authors.lastname: Herrera-Marschitz
authors.affiliation: Program of Physiology & Biophysics, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile; Biomedical Neuroscience Institute, BNI, ICBM, Faculty of Medicine, University of Chile, Av. Independencia 1027, Santiago, Chile. Electronic address: jlvaldes@med.uchile.cl.
authors.forename: José L
authors.initials: JL
authors.lastname: Valdés
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006632:Histamine / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D011968:Receptors, Histamine / Q000187:drug effects
chemical_list: D006633:Histamine Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011968:Receptors, Histamine; D006632:Histamine; D004298:Dopamine
keywords: Adenosine deaminase; Histidine decarboxylase; Hypoxia; Object recognition; Perinatal asphyxia; Tuberomammillary nucleus