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Excessive accumulation of amyloid beta (Abeta) has been proposed as a pivotal event in the pathogenesis of Alzheimer's disease. Possible mechanisms underlying Abeta-induced neuronal cytotoxicity include excess production of reactive oxidative species (ROS) and apoptosis. Neuroglobin (Ngb), a newly discovered globin in vertebrates that exhibits neuroprotective functions, may have a potential role in scavenging ROS. To examine the potential protective role of Ngb in Abeta-induced cytotoxicity, PC12 cells were treated with Abeta (1-42 fragment) for 24h. Abeta treatments increased ROS production in PC12 cells. Overexpression of Ngb but not Ngb mutant in the PC12 cells significantly attenuated Abeta-induced ROS production and lipids peroxidation. Furthermore, overexpression of Ngb also attenuated Abeta-induced mitochondrial dysfunction and apoptosis, and promoted cell survival in PC12 cells. Therefore, Ngb may act as an intracellular ROS scavenger, and such antioxidant properties may play a protective role against Abeta-induced cell injury.

Purpose Intracerebroventricular (ICV) administration of ouabain, a potent sodium pump inhibitor, has been used to model mania. Antipsychotic agents have demonstrated efficacy in the management of acute mania. This study was undertaken to determine the prophylactic efficacy of olanzapine and haloperidol in the ouabain mania model. Methods Male Sprague–Dawley rats (4–8/group) were treated with two haloperidol decanoate intramuscular shots one week apart (21 mg/kg) or twice daily olanzapine intraperitoneal injections at low dose (1 mg/kg/day) or high dose (6 mg/kg/day) for 7 days prior to ICV administration of ouabain. Open field locomotion was quantified at baseline and after ouabain administration. Results Ouabain caused a significant increase in open field locomotion (253.7 ± SEM 55.12 vs control 53.1 ± 12.13 squares traversed in 30 min in the olanzapine experiments, P

Neuroglobin (Ngb) is a newly discovered globin in the vertebrate brain that exhibits neuroprotection against hypoxic/ischemic injury. Hypoxic/ischemic brain injury is associated with accumulation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS), and antioxidants or ROS scavengers promote cell survival. Therefore, Ngb may serve as a scavenger of toxic reactive species, such as hydrogen peroxide. To examine the anti-oxidative role of neuroglobin, PC12 cells were transfected with wild type and mutant (H64 V/H96A) Ngb for 48 h and then treated with H2O2 (0.1, 0.2 and 0.4 mM) for 6 h. Ngb siRNA decreased the H2O2-induced Ngb expression and exacerbated H2O2-induced cell injury. Transient transfection of Ngb induced dose-dependent increases in Ngb protein expression and did not alter SOD, GPX, and catalase activities. Overexpression of wild type Ngb, but not of mutant Ngb, significantly attenuated H2O2-induced ROS/RNS accumulation and lipid peroxidation, decreased H2O2-induced mitochondrial dysfunction and apoptosis, and promoted overall cell survival. Thus, Ngb plays a protective role against oxidative stress, which appears to be primarily mediated by intrinsic Ngb antioxidant properties.