title: Neuroprotective effects of hypothermia on synaptic actin cytoskeletal changes induced by perinatal asphyxia.
abstract: Cerebral hypoxia-ischemia damages synaptic proteins, resulting in cytoskeletal alterations, protein aggregation and neuronal death. In the previous works, we have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia that leads to ubi-protein accumulation. Recently, we also showed that, changes in F-actin organization could be related to early alterations induced by hypoxia in the Central Nervous System. However, little is known about effective treatment to diminish the damage. The main aim of this work is to study the effects of birth hypothermia on the actin cytoskeleton of neostriatal post-synaptic densities (PSD) in 60 days olds rats by immunohistochemistry, photooxidation and western blot. We used 2 different protocols of hypothermia: (a) intrahypoxic hypothermia at 15°C and (b) post-hypoxia hypothermia at 32°C. Consistent with previous data at 30 days, staining with phalloidin-Alexa(488) followed by confocal microscopy analysis showed an increase of F-actin fluorescent staining in the neostriatum of hypoxic animals. Correlative photooxidation electron microscopy confirmed these observations showing an increment in the number of mushroom-shaped F-actin staining spines in neostriatal excitatory synapses in rats subjected to hypoxia. In addition, western blot revealed β-actin increase in PSDs in hypoxic animals. The optic relative density measurement showed a significant difference between controls and hypoxic animals. When hypoxia was induced under hypothermic conditions, the changes observed in actin cytoskeleton were blocked. Post-hypoxic hypothermia showed similar answer but actin cytoskeleton modifications were not totally reverted as we observed at 15°C. These data suggest that the decrease of the body temperature decreases the actin modifications in dendritic spines preventing the neuronal death.
authors.affiliation: Laboratorio de Citoarquitectura y Plasticidad Neuronal, Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), UBA-CONICET, C1122AAJ, Buenos Aires, Argentina.
authors.forename: Javier
authors.initials: J
authors.lastname: Muñiz
authors.affiliation: Laboratorio de Citoarquitectura y Plasticidad Neuronal, Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), UBA-CONICET, C1122AAJ, Buenos Aires, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Romero
authors.affiliation: Laboratorio de Citoarquitectura y Plasticidad Neuronal, Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), UBA-CONICET, C1122AAJ, Buenos Aires, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Holubiec
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá DC, Colombia.
authors.forename: George
authors.initials: G
authors.lastname: Barreto
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá DC, Colombia.
authors.forename: Janneth
authors.initials: J
authors.lastname: González
authors.affiliation: Laboratorio de Citoarquitectura y Plasticidad Neuronal, Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), UBA-CONICET, C1122AAJ, Buenos Aires, Argentina.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Saint-Martin
authors.affiliation: Laboratorio de Citoarquitectura y Plasticidad Neuronal, Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), UBA-CONICET, C1122AAJ, Buenos Aires, Argentina; Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Blanco
authors.affiliation: Instituto de Histología y Embriología "Dr. Mario H. Burgos" (IHEM-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Carlos Cavicchia
authors.affiliation: Laboratorio de Citoarquitectura y Plasticidad Neuronal, Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), UBA-CONICET, C1122AAJ, Buenos Aires, Argentina.
authors.forename: Rocío
authors.initials: R
authors.lastname: Castilla
authors.affiliation: Laboratorio de Citoarquitectura y Plasticidad Neuronal, Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), UBA-CONICET, C1122AAJ, Buenos Aires, Argentina; Departamento de Biología, Universidad Argentina John F Kennedy, Buenos Aires, Argentina. Electronic address: fcapani@fmed.uba.ar.
authors.forename: Francisco
authors.initials: F
authors.lastname: Capani
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001238:Asphyxia Neonatorum / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D059330:GABAergic Neurons / Q000473:pathology; D007036:Hypothermia, Induced; D017072:Neostriatum / Q000378:metabolism*; D057907:Post-Synaptic Density / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000199:Actins
keywords: Actin cytoskeleton; Hypothermia; Neostriatum; Neuroprotection; Perinatal asphyxia