ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective loss of motor neurons. Although organotypic spinal slice cultures (OSCs) exposed to inhibitors of glutamate uptake have been used as a model of ALS for screening of potentially therapeutic drugs, little development of such drugs has been achieved. In the present study we attempted to establish OSCs from G93A SOD1 transgenic mice (G93A) and to characterize the specific cell death pathway in motoneurons using glial cell line-derived neurotrophic factor (GDNF) in these mice. In the presence of GDNF, the number of surviving neurons in the OSCs was dramatically increased in both G93A and control mice. Exposure to threo-hydroxyaspartate (THA), a glutamate transport inhibitor, for 14 days induced loss of motoneurons in OSCs in G93A and control mice. In OSCs cultured with GDNF, THA-induced motoneuronal death was significantly inhibited in G93A mice, whereas that in control mice was not significantly affected. Moreover, the cleaved form of caspase-12 was increased after THA in the OSCs in G93A but not in control mice, and the activation of caspase-12 was attenuated by OSCs cultured with GDNF. These results suggest that the pathway responsible for motoneuronal death induced by THA in OSCs in G93A mice involves not only in excitotoxicity but also other mechanisms, and that the caspase-12-dependent ER stress pathway plays a role in spinal neuronal death in G93A mice. Moreover, OSCs prepared from the G93A mouse model of ALS may provide a suitable in vitro drug screening model for ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/physiopathology , Glutamic Acid/toxicity , Motor Neurons/drug effects , Spinal Cord/drug effects , Amyotrophic Lateral Sclerosis/pathology , Animals , Aspartic Acid/analogs & derivatives , Aspartic Acid/toxicity , Caspase 12/metabolism , Cell Death/drug effects , Cell Survival/drug effects , Cell Survival/physiology , Disease Models, Animal , Enzyme Activation/drug effects , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Mice , Mice, Transgenic , Organ Culture Techniques , Spinal Cord/physiopathology , Superoxide Dismutase/geneticsABSTRACT
PURPOSE: Appropriate initial education for type-1 diabetes mellitus patients is important to prevent late complications. However, type-1 diabetic children have not appreciated traditional learning methods since they rarely contain the elements of fun and interactivity. In this study, we developed, implemented and evaluated a preliminary version of edutainment tools for initial education for type-1 diabetic children. METHODS: Three games running on either personal computer (PC) and GameBoy Advance were developed. All games were designed to educate patients about relationships among food (carbohydrate), plasma glucose level, exercise, and insulin dose. A total of 58 testers evaluated degree of entertainment, usability and clinical usefulness of the games. RESULTS: Generally, testers felt all games were intuitive and fun and the usability of games was highly scored. More than 90% of testers showed an interest in the edutainment approach, and approximately 60% agreed that these games could provide attractive educational environment compared to traditional education, especially for children. CONCLUSIONS: Our edutainment systems were accepted as attractive learning tools for type-1 diabetic children who need initial education.
