title: Short-term psychosocial stress protects photoreceptors from damage via corticosterone-mediated activation of the AKT pathway.
abstract: Apoptotic death of photoreceptors in hereditary retinal degenerations can be prevented by neuroprotective molecules. Here, we report that adrenal glucocorticoids (GC) released during psychosocial stress protect photoreceptors from apoptosis after light damage. Psychosocial stress is known to be the main type of stressor humans are exposed to and was induced here in mice by 10h of chronic subordinate colony housing (CSC). Photoreceptor damage was generated by subsequent exposure to white light. Short-term psychosocial stress prior to illumination significantly reduced the number of apoptotic photoreceptors, an effect that was absent in adrenalectomized (ADX) mice. The neuroprotective effect was completely restored in ADX mice substituted with GC. Moreover, phosphorylation of retinal AKT increased following CSC or exogenous GC treatment, an effect that was again absent in ADX mice exposed to CSC. Finally, inhibition of AKT signaling with triciribine blocked the stress- and GC-mediated neuroprotective effects on photoreceptors. In summary, we provide evidence that 1) short-term psychosocial stress protects photoreceptors from light-induced damage and 2) the protective effect is most likely mediated by GC-induced activation of the AKT signaling pathway.
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: Tembei K
authors.initials: TK
authors.lastname: Forkwa
authors.affiliation: Department of Behavioral and Molecular Neurobiology, Institute of Zoology, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: Inga D
authors.initials: ID
authors.lastname: Neumann
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, 93053 Regensburg, Germany.
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, 93053 Regensburg, Germany. Electronic address: andreas.ohlmann@vkl.uni-regensburg.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ohlmann
authors.affiliation: Department of Behavioral and Molecular Neurobiology, Institute of Zoology, University of Regensburg, 93053 Regensburg, Germany; Laboratory for Molecular Psychosomatics, Clinic for Psychosomatic Medicine and Psychotherapy, University of Ulm, 89081 Ulm, Germany.
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Reber
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D003345:Corticosterone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D019333:Endothelin-2 / Q000235:genetics / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism; D008027:Light / Q000009:adverse effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects*; D012162:Retinal Degeneration / Q000209:etiology / Q000517:prevention & control*; D012263:Ribonucleosides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013315:Stress, Psychological / Q000150:complications / Q000473:pathology*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D019333:Endothelin-2; D005904:Glial Fibrillary Acidic Protein; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D012263:Ribonucleosides; D016222:Fibroblast Growth Factor 2; C023764:triciribine; D003345:Corticosterone
keywords: AKT signaling; Apoptosis; Chronic subordinate colony housing; Glucocorticoids; Hypothalamo-pituitary–adrenocortical axis; Light-induced photoreceptor damage; Neuroprotection; Photoreceptor degeneration; Psychosocial stress