title: Astroglia-Microglia Cross Talk during Neurodegeneration in the Rat Hippocampus.
abstract: Brain injury triggers a progressive inflammatory response supported by a dynamic astroglia-microglia interplay. We investigated the progressive chronic features of the astroglia-microglia cross talk in the perspective of neuronal effects in a rat model of hippocampal excitotoxic injury. N-Methyl-D-aspartate (NMDA) injection triggered a process characterized within 38 days by atrophy, neuronal loss, and fast astroglia-mediated S100B increase. Microglia reaction varied with the lesion progression. It presented a peak of tumor necrosis factor-α (TNF-α) secretion at one day after the lesion, and a transient YM1 secretion within the first three days. Microglial glucocorticoid receptor expression increased up to day 5, before returning progressively to sham values. To further investigate the astroglia role in the microglia reaction, we performed concomitant transient astroglia ablation with L-α-aminoadipate and NMDA-induced lesion. We observed a striking maintenance of neuronal death associated with enhanced microglial reaction and proliferation, increased YM1 concentration, and decreased TNF-α secretion and glucocorticoid receptor expression. S100B reactivity only increased after astroglia recovery. Our results argue for an initial neuroprotective microglial reaction, with a direct astroglial control of the microglial cytotoxic response. We propose the recovery of the astroglia-microglia cross talk as a tissue priority conducted to ensure a proper cellular coordination that retails brain damage.
authors.affiliation: Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Batlle
authors.affiliation: Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain ; Istituto di Anatomia Umana e Biologia Cellulare, Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ferri
authors.affiliation: Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Andrade
authors.affiliation: Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain ; Vall d'Hebron Institute of Research (VHIR), Passeig de la Vall d'Hebron 119, 08035 Barcelona, Spain.
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Ortega
authors.affiliation: Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Vidal-Taboada
authors.affiliation: Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain ; Vall d'Hebron Institute of Research (VHIR), Passeig de la Vall d'Hebron 119, 08035 Barcelona, Spain.
authors.forename: Marco
authors.initials: M
authors.lastname: Pugliese
authors.affiliation: Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mahy
authors.affiliation: Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Rodríguez
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016202:N-Methylaspartate / Q000008:administration & dosage; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D011965:Receptors, Glucocorticoid; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; D014409:Tumor Necrosis Factor-alpha; D016202:N-Methylaspartate; D001619:beta-N-Acetylhexosaminidases