| First Author | Shichiri M | Year | 2021 |
| Journal | Free Radic Biol Med | Volume | 175 |
| Pages | 171-183 | PubMed ID | 34474105 |
| Mgi Jnum | J:313589 | Mgi Id | MGI:6789379 |
| Doi | 10.1016/j.freeradbiomed.2021.08.236 | Citation | Shichiri M, et al. (2021) Stress-activated leukocyte 12/15-lipoxygenase metabolite enhances struggle behaviour and tocotrienols relieve stress-induced behaviour alteration. Free Radic Biol Med 175:171-183 |
| abstractText | Stress induces emotional arousal causing anxiety, irritability, exaggerated startle behaviour, and hypervigilance observed in patients with trauma and stress-related mental disorders, including acute stress disorder and post-traumatic stress disorder. Central norepinephrine release promotes stress-induced emotional arousal. However, the regulator of emotional arousal remains unknown. Here, we show that the arachidonate-derived metabolite produced by stress-activated leukocyte 12/15-lipoxygenase is remarkably elevated in the plasma and upregulates the central norepinephrine release, resulting in the enhancement of the struggle behaviour (= escape behaviour) in the tail suspension test. Struggle behaviour is mimicking a symptom of emotional arousal. This stress-induced struggle behaviour was absent in 12/15-lipoxygenase deficient mice; however, intravenous administration of a 12/15-lipoxygenase metabolite to these mice after stress exposure rekindled the struggle behaviour. Furthermore, tocotrienols and geranylgeraniol reduced stress-induced 12/15-lipoxygenase metabolite production and suppressed the struggle behaviour. Our findings indicate that arachidonate-derived 12/15-lipoxygenase metabolite is involved in the regulation of stress-enhanced central norepinephrine release and struggle behaviour. In addition, we propose 12/15-lipoxygenase as a potential therapeutic target for the treatment of emotional arousal observed in stress-related mental disorders. |
