Fucoxanthin, a marine derived carotenoid, attenuates surgery-induced cognitive impairments via activating Akt and ERK pathways in aged mice.

BACKGROUND: Fucoxanthin is the most abundant marine carotenoid derived from brown seaweeds, possesses antioxidant, anti-inflammatory, and neuroprotective properties, and might be benefit for the treatment of neurological disorders. Post-operative cognitive dysfunction (POCD) is a neurological symptom with learning and memory impairments, mainly affecting the elderly after surgery. However, there is no effective treatments for this symptom. PURPOSES: In this study, we evaluated the neuroprotective effects of fucoxanthin against POCD in aged mice after surgery. STUDY DESIGN AND METHODS: The animal model of POCD was established in 12 - 14 month aged mice with a laparotomy. Curcumin was used as a positive control. The beneficial effects of fucoxanthin on POCD was analyzed by behavioral tests. Pro-inflammatory cytokines were measured by Enzyme-linked Immunosorbent Assay (ELISA). And the expressions of key proteins in the Akt and ERK signaling pathways were analyzed by Western blotting analysis. The morphology of microglial cells and astrocytes was explored by immunohistochemical staining. The activity of antioxidant superoxide dismutase (SOD) and catalase (CAT) were measured by anti-oxidative enzyme activity assays. RESULTS: Fucoxanthin at 100 - 200 mg/kg significantly attenuated cognitive dysfunction, with a similar potency as curcumin, in aged mice after surgery. In addition, fucoxanthin and curcumin significantly increased the expression of pAkt, prevented the activation of microglial cells and astrocytes, and inhibited the secretion of pro-inflammatory interleukin-1ß (IL - 1ß) and tumor necrosis factor-α (TNF-α). Furthermore, fucoxanthin and curcumin elevated the ERK pathway and potently increased the activity of antioxidant enzymes. Most importantly, U0126, an inhibitor of the ERK pathway, and wortmannin, an inhibitor of the Akt pathway, significantly abolished the cognitive-enhancing effects, as well as the inhibition of neuroinflammation and the reduction of oxidative stress, induced by fucoxanthin in aged mice after surgery. CONCLUSION: Fucoxanthin might be developed as a functional food or drug for the treatment of POCD by inhibiting neuroinflammation and enhancing antioxidant capacity via the activation of the Akt and ERK signaling pathways.

Chronic multiple mild stress induces sustained adverse psychological states in rats.

Adverse psychological states are stimulated by multiple types of environmental factors in human being. However, only few animal models of adverse psychological states were established by applying multiple types of stressors to mimic real conditions. A multisensory stress simulation device was designed to apply a combination of stressors to animals. Selected types and intensity of stressors were stimulated by this multisensory stress simulation device to induce chronic multiple mild stress (CMMS) in rats, modeling sustained adverse psychological states caused by long-term exposure in relative extreme environments with limited social interaction in human being. Fourteen-day treatment of CMMS-induced anhedonia, anxiety, and the loss of body weight in rats, which were similar to those in human being with adverse psychological states. Moreover, CMMS treatment leads to decreased production of serotonin and increased expression of corticotropin-releasing factor receptor 1, adrenocorticotropic hormone, and glucocorticoid in the brain, which were prevented by paroxetine and sertraline, two clinical-used antidepressants. Furthermore, these antidepressants prevented the CMMS-induced inhibition of brain-derived neurotrophic factor/cAMP-response element binding protein pathway, reduction of synaptic protein expression, and the activation of microglia and astrocytes in the hippocampus and the prefrontal cortex of rats. In addition, 14-day CMMS-induced long-term depressive-like behaviors, even after 14 days of CMMS treatment. And sertraline reversed CMMS-induced behavioral and biochemical changes in rats. All these results suggested that CMMS protocol induced sustained adverse psychological states in rats. By adjusting the intensity and the type of stressors in the multisensory stress simulation device, it might be practicable to establish animal models with complicated and changeable environmental factors.