Monoamine oxidase–B (MAO-B) has recently emerged as a potential therapeutic target for Alzheimer’s disease (AD) because of its association with aberrant γ-aminobutyric acid (GABA) production in reactive astrocytes. Although short-term treatment with irreversible MAO-B inhibitors, such as selegiline, improves cognitive deficits in AD patients, long-term treatments have shown disappointing results. We show that prolonged treatment with selegiline fails to reduce aberrant astrocytic GABA levels and rescue memory impairment in APP/PS1 mice, an animal model of AD, because of increased activity in compensatory genes for a GABA-synthesizing enzyme, diamine oxidase (DAO). We have developed a potent, highly selective, and reversible MAO-B inhibitor, KDS2010 (IC50 = 7.6 nM; 12,500-fold selectivity over MAO-A), which overcomes the disadvantages of the irreversible MAO-B inhibitor. Long-term treatment with KDS2010 does not induce compensatory mechanisms, thereby significantly attenuating increased astrocytic GABA levels and astrogliosis, enhancing synaptic transmission, and rescuing learning and memory impairments in APP/PS1 mice.
Highlights d Reactive astrocytes in SNpc produce excessive GABA via MAO-B in animal models of PD d Aberrant tonic inhibition causes reduced DA production in neurons and motor deficits d Dormant neurons are rescued by MAO-B inhibition or optogenetic neuronal activation
As the number of internet users increases, a new game genre using the internet as a networking tool is emerging. Some game genres are regarded as having greater addiction potentials than others. Games and the internet are closely related. We investigated games frequently used by adolescents and classified each of them with the help of game professionals. We also examined internet use patterns to identify relationships between game genre and internet use patterns. 627 middle school and high school students (male 488, female 139) completed questionnaires concerning computer and game use patterns and Korean internet addiction scales. Game genres were divided into eight criteria (simulation, role playing game, web board, community, action, adventure, shooting, and sports). Using Korean internet addiction scales, 627 participants were divided into a normal group (474), a potential risk group (128), and a high-risk group (25). Each group showed significant differences in total internet addiction scores. We classified players into specific game users based upon the game types they most prefer. Role playing game users showed significantly higher internet addiction scores than web board and sports game users. Game and internet addictions are also connected with interpersonal relationship patterns. We suggest that users of some game genre have unique psychological addiction potentials that are different from others and that this influences both game selection and internet use.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.