title: Underwater trauma causes a long-term specific increase in the expression of cyclooxygenase-2 in the ventral CA₁ of the hippocampus.
abstract: The pro-inflammatory enzyme cyclooxygenase-2 (COX-2) is regularly expressed in the hippocampal neurons, but its role in emotional trauma is not known. Here we show that a single acute stress caused by a near-drowning experience results in heightened anxiety-like behavior one month after the trauma. Biochemical analyses of dorsal and ventral hippocampal CA1, CA3 and dentate gyrus revealed decreased ubiquitination and elevated levels of COX-2 in the traumatized animals only in the ventral CA1. To reveal the identity of the ubiquitin E3 ligase that targets COX-2, we tested the effect of several representative E3 ligases on COX-2 expression in vitro. We found that while AIP4 and Nedd4 had no effect, Mdm2 lowered COX-2 expression by nearly 50%, an effect that was not observed by its dominant negative form. To test whether this also occurs in the hippocampus, we immunoprecipitated Mdm2 from dorsal and ventral CA1 of traumatized and control animals and probed for the presence of COX-2. Our results showed that the levels of Mdm2 were not affected by the trauma but there was significantly less COX-2 associated with Mdm2 in the ventral but not dorsal CA1 of the traumatized animals. Together these data propose that an increase in COX-2 expression in ventral CA1 following trauma is likely due to its attenuated degradation. Unraveling the pathways and mechanisms that control hippocampal COX-2 degradation is important to boost the development of novel therapeutic approaches designed to treat stress-related pathologies.
authors: Department of Human Biology, Faculty of Natural Sciences, University of Haifa, 199 Aba Khoushy Ave. Mt. Carmel, Haifa 3498838, Israel.
authors: Rapita
authors: R
authors: Sood
authors: The Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, 199 Aba Khoushy Ave. Mt. Carmel, Haifa 3498838, Israel; The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, 199 Aba Khoushy Ave. Mt. Carmel, Haifa 3498838, Israel.
authors: Gilad
authors: G
authors: Ritov
authors: The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, 199 Aba Khoushy Ave. Mt. Carmel, Haifa 3498838, Israel.
authors: Boris
authors: B
authors: Boltyansky
authors: Department of Human Biology, Faculty of Natural Sciences, University of Haifa, 199 Aba Khoushy Ave. Mt. Carmel, Haifa 3498838, Israel.
authors: Almog
authors: A
authors: Spector-Chotiner
authors: The Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, 199 Aba Khoushy Ave. Mt. Carmel, Haifa 3498838, Israel; The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, 199 Aba Khoushy Ave. Mt. Carmel, Haifa 3498838, Israel; Department of Psychology, Faculty of Social Sciences, University of Haifa, 199 Aba Khoushy Ave. Mt. Carmel, Haifa 3498838, Israel.
authors: Gal
authors: G
authors: Richter-Levin
authors: Department of Human Biology, Faculty of Natural Sciences, University of Haifa, 199 Aba Khoushy Ave. Mt. Carmel, Haifa 3498838, Israel. Electronic address: lbarki@psy.haifa.ac.il.
authors: Liza
authors: L
authors: Barki-Harrington
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006041:Goats; D008297:Male; D051379:Mice; D015701:Near Drowning / Q000378:metabolism* / Q000523:psychology; D051381:Rats; D013315:Stress, Psychological / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D051546:Cyclooxygenase 2; D044767:Ubiquitin-Protein Ligases
keywords: Cyclooxygenase-2; Elevated plus maze; Emotional trauma; Hippocampus; Mdm2; Post trauma; Ubiquitination; Underwater trauma