title: Forced swimming sabotages the morphological and synaptic maturation of newborn granule neurons and triggers a unique pro-inflammatory milieu in the hippocampus.
abstract: Recent experimental data suggest that mood disorders are related to inflammatory phenomena and have led to the "inflammatory hypothesis of depression". Given that the hippocampus is one of the most affected areas in these disorders, we used a model of acute stress (the Porsolt test) to evaluate the consequences of forced swimming on two crucial events related to the pathophysiology of major depression: the functional maturation of newborn granule neurons; and the hippocampal inflammatory milieu. Using PSD95:GFP-expressing retroviruses, we found that forced swimming selectively alters the dendritic morphology of newborn neurons and impairs their connectivity by reducing the number and volume of their postsynaptic densities. In addition, acute stress triggered a series of morphological changes in microglial cells, together with an increase in microglial CD68 expression, thus suggesting the functional and morphological activation of this cell population. Furthermore, we observed an intriguing change in the hippocampal inflammatory milieu in response to forced swimming. Importantly, the levels of several molecules affected by acute stress (such as Interleukin-6 and eotaxin) have been described to also be altered in patients with depression and other mood disorders.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), c/ Nicolás Cabrera 1, 28049 Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), c/ Valderrebollo 5, Madrid, Spain. Electronic address: m.llorens@csic.es.
authors.forename: María
authors.initials: M
authors.lastname: Llorens-Martín
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), c/ Nicolás Cabrera 1, 28049 Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), c/ Valderrebollo 5, Madrid, Spain.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Jurado-Arjona
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), c/ Nicolás Cabrera 1, 28049 Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), c/ Valderrebollo 5, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bolós
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), c/ Nicolás Cabrera 1, 28049 Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), c/ Valderrebollo 5, Madrid, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Pallas-Bazarra
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), c/ Nicolás Cabrera 1, 28049 Madrid, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), c/ Valderrebollo 5, Madrid, Spain. Electronic address: javila@cbm.csic.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ávila
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D003863:Depression / Q000378:metabolism / Q000473:pathology; D003865:Major Depressive Disorder / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D023421:Models, Animal; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*; D013550:Swimming
keywords: Acute stress; Adult hippocampal neurogenesis; Forced swimming; Inflammation; Microglia; Retrovirus