Prostaglandin E2 (PGE2) was shown to induce neuronal death in the CNS. To characterize the neurotoxicity of PGE2 and E-prostanoid receptors (EP) in motor neurons, we investigated PGE2-induced cell death and the type(s) of EP responsible for mediating it in NSC-34, a motor neuron-like cell line. Immunoblotting studies showed that EP2 and EP3 were dominantly expressed in NSC-34 cells and motor neurons in mice. Exposure to PGE2 and butaprost, an EP2 agonist, but not sulprostone, an EP1/3 agonist, resulted in decreased viability of these cells. These results suggest that PGE2 induces cell death by activation of EP2 in NSC-34 cells.

Amyotrophic lateral sclerosis (ALS) is an adult-onset, progressive, and fatal neurodegenerative disease caused by selective loss of motor neurons. Both ALS model mice and patients with sporadic ALS have increased levels of prostaglandin E2 (PGE2). Furthermore, the protein levels of microsomal PGE synthase-1 and cyclooxygenase-2, which catalyze PGE2 biosynthesis, are significantly increased in the spinal cord of ALS model mice. However, it is unclear whether PGE2 metabolism in the spinal cord is altered. In the present study, we investigated the protein level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key enzyme in prostaglandin metabolism, in ALS model mice at three different disease stages. Western blotting revealed that the 15-PGDH level was significantly increased in the lumbar spinal cord at the symptomatic stage and end stage. Immunohistochemical staining demonstrated that 15-PGDH immunoreactivity was localized in glial fibrillary acidic protein (GFAP)-positive astrocytes at the end stage. In contrast, 15-PGDH immunoreactivity was not identified in NeuN-positive large cells showing the typical morphology of motor neurons in the anterior horn. Unlike 15-PGDH, the level of PGE2 in the spinal cord was increased only at the end stage. These results suggest that the significant increase of PGE2 at the end stage of ALS in this mouse model is attributable to an imbalance of the synthetic pathway and 15-PGDH-dependent scavenging system for PGE2, and that this drives the pathogenetic mechanism responsible for transition from the symptomatic stage.

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We have developed a signalling system which controls signal devices through an IP-Network. This system consists of a Logic Controller (LC) and Field Controllers (FCs) connected with optical cable. The LC is a safety-related device located at the signal house. The LC generates the command data, and transmits the data to the FCs through IP-Network. The FC is a safety-related device equipped in each signal device, and controls the device based on the command data from the LC. In the railway signalling system, high level of safety and reliability are required. In this system, the transmission devices and protocol are based on the general technologies. Therefore, we need to assume all kinds of errors on the transmission devices, and the whole system must keep itself in safe status even if the worst error occurs. In order to comply with the IEC62280-1, we have developed a safety transmission protocol. Moreover, this system needs to operate for 20 years without system down. We have defined the target of the failure rate of each device less than 10 -7 /h. We measured the traffic limitation in order to validate the reliability about the transmission between the LC and the FC, and confirmed that the traffic is much less than the traffic limitation of the transmission device. We have evaluated the safety and reliability of this system with prototype system, and put this system into practical use at Ichikawaono station on the Musashino line in February 2007.

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