Brain research
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Interleukin-1 beta (IL-1β) is one of pro-inflammatory cytokines. Recent studies have shown that IL-1β impairs hippocampal neurogenesis, mediates proliferation and differentiation of multipotent neural precursor cells (NPCs), and exerts effects of anti-proliferation, anti-neurogenesis, and pro-gliogenesis on embryonic hippocampal NPCs. The aim of this study was to examine the effect of IL-1β on the differentiation of hippocampal NPCs into functional serotonergic neurons, which play important roles in the pathophysiology and treatment of depression. ⋯ After three passages and phenotyping, hippocampal NPCs were cultured in a differentiating medium with various concentrations (5, 10, and 20 ng/mL) of IL-1β for 7 days. At the endpoint, the serotonergic differentiation of hippocampal NPCs in IL-1β-treated cultures decreased in a dose-dependent manner and this effect was blocked by IL-1ra, an IL-1 receptor antagonist capable of blocking the effects of IL-1 by binding to the same receptor (IL-1R1) without triggering signaling; serotonin in the lysate of the differentiated hippocampal NPCs decreased in IL-1β-treated cultures; and levels of Bcl-2 and phosphorylated extracellular-regulated kinase (pERK) were also lower in differentiated hippocampal NPCs with IL-1β treatment. These results support the hypothesis that IL-1β is an important factor in the stress-associated neuropathology and psychopathology and has relevance to the treatment of depressive symptoms in patients with depression.
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Traumatic axonal injury (TAI), a feature of traumatic brain injury (TBI), progressively evolves over hours through impaired axonal transport and is thought to be a major contributor to cognitive dysfunction. In spite of various studies suggesting that pharmacologic or physiologic interventions might reduce TAI, clinical neuroprotective treatments are still unavailable. Edaravone, a free radical scavenger, has been shown to exert neuroprotective effects in animal models of several brain disorders. ⋯ With treatment 1h after impact, axonal injury was also significantly suppressed and this therapeutic effect persisted up to 6h after impact. Furthermore, behavioral tests performed 9 days after injury showed memory deficits in saline-treated traumatized mice, which were not evident in the edaravone-treated group. These results suggest that edaravone protects against memory deficits following TBI and that this protection is mediated by suppression of TAI and oxidative stress.