Do Event-Related Evoked Potentials Reflect Apathy Tendency and Motivation?

Apathy is a mental state of diminished motivation. Although the reward system as the foundation of the motivation in the human brain has been studied extensively with neuroimaging techniques, the electrophysiological correlates of motivation and apathy have not been fully explored. Thus, in 14 healthy volunteers, we examined whether event-related evoked potentials (ERP) obtained during a simple number discrimination task with/without rewards reflected apathy tendency and a reward-dependent tendency, which were assessed separately using the apathy scale and the temperament and character inventory (TCI). Participants were asked to judge the size of a number, and received feedback based on their performance in each trial. The P3 amplitudes related to the feedback stimuli increased only in the reward condition. Furthermore, the P2 amplitudes related to the negative feedback stimuli in the reward condition had a positive correlation with the reward-dependent tendency in TCI, whereas the P3 amplitudes related to the positive feedback stimuli had a negative correlation with the apathy score. Our result suggests that the P2 and P3 ERPs to reward-related feedback stimuli are modulated in a distinctive manner by the motivational reward dependence and apathy tendency, and thus the current paradigm may be useful for investigating the brain activity associated with motivation

Bulk Functional Materials Design Using Oxide Nanosheets as Building Blocks: A New Upconversion Material Fabricated by Flocculation of Ca₂Nb₃O₁₀^– Nanosheets with Rare-Earth Ions

A new upconversion (UC) material was designed by flocculating a Ca₂Nb₃O₁₀^– nanosheet, which acts as thermal and structural stabilizer, with Ho³⁺ photoactivator, Yb³⁺ sensitizer, and Y³⁺ space filler. The flocculated product consists of the restacked nanosheets and the rare-earth ions in the internanosheet gallery. The restacked sheet faces of the Ca₂Nb₃O₁₀^– nanosheet building blocks are self-organized in a parallel manner, and their crystallographic coherency extends to three layers on average. On the other hand, the nanosheet building blocks are randomly staggered along the in-layer direction. Chemical composition of the flocculated product was estimated as (Ho_0.096Yb_0.23Y_0.164)­Ca_1.76□_0.24Nb₃O₁₀·1.4H₂O. Heat treatment of the flocculated product at 500 °C was necessary in order to suppress nonradiative energy loss via OH vibration and to induce UC emission. Even after the heat treatment, perovskite-type atomic arrangement of the Ca₂Nb₃O₁₀^– nanosheet building block was retained. Upon laser irradiation at 980 nm, two UC emission bands around 550 and 660 nm were observed, and the emission was visible to the eye. The result from this study suggests that flocculation of nanosheets, as building blocks, with counterions is a promising way to design bulk functional materials that are rather difficult or impossible to prepare by conventional synthetic approaches

Design, synthesis and radioprotecting activity of metal-chelator and hydroxyquinoline-based derivatives.

In radiation therapy, adverse side effects are often induced due to the excessive cell death that occurs in radiosensitive normal cells. Therefore, radioprotective drugs that can protect normal cells from radiation and thus suppress adverse side effects would be highly desirable. The radiation-induced cell death of normal cells is caused, at least in part, by apoptosis, which undergoes via activation of p53 and increase in the p53 protein, a zinc-containing transcriptional factor, in response to cellular damage. The mechanisms responsible for p53-induced apoptosis are classified into a transcription-dependent pathway and a transcription-independent pathway. In this paper, we report on the radioprotective activity of Zn2+ chelators such as TPEN (Tetrakis(2-pyridylmethyl)ethylenediamine) and bispicen (N,N’-Bis(2-pyridylmethyl)-1,2-ethanediamine) , and 8-hydroxyquinoline (8HQ) derivatives that were designed so as to interact with the Zn2+ in p53. It was revealed that bispicen induces a conformational change in p53, resulting in inhibition of its complexation with DNA and the inhibition of both the p53-mediated transcription-dependent and independent pathways (Oncotarget, 4, 2439-2450, 2013).As for the 8HQ derivatives, the 5,7-bis(methylaminosulfonyl)-8HQ and 8-methoxyquinoline derivatives considerably protected MOLT-4 cells against g-ray radiation (10 Gy), accompanied by a low cytotoxicity. Mechanistic studies revealed that the interaction of these drugs with p53 is weak and the mechanism for inhibiting apoptosis appears to be different from that of previously reported radioprotectors such as bispicen, which inhibits apoptosis via the denaturation of p53 as well as by blocking both transcription-dependent and –independent apoptotic pathways (Bioorg. Med. Chem. 22, 3891-3905, 2014; Biochem. Biophys. Res. Commun. 450, 1498-1504, 2014). Key words: 8-Hydroxyquinoline, Radioprotector, Mechanistic study日本放射線影響学会第58回大会(学会出席・発表)参加日程: 平成27年5月25日〜29

Validation of a new mass screening tool for cognitive impairment: Cognitive Assessment for Dementia, iPad version

Keiichi Onoda,1 Tsuyoshi Hamano,2 Yoko Nabika,1 Atsuo Aoyama,1 Hiroyuki Takayoshi,1 Tomonori Nakagawa,1 Masaki Ishihara,1 Shingo Mitaki,1 Takuya Yamaguchi,1 Hiroaki Oguro,1 Kuninori Shiwaku,3 Shuhei Yamaguchi1 1Department of Neurology, 2Center for Community-Based Health Research and Education, Shimane University, Izumo, 3Shimane University, Matsue, Shimane, Japan Background: We have developed a new screening test for dementia that runs on an iPad and can be used for mass screening, known as the Cognitive Assessment for Dementia, iPad version (CADi). The CADi consists of items involving immediate recognition memory for three words, semantic memory, categorization of six objects, subtraction, backward repetition of digits, cube rotation, pyramid rotation, trail making A, trail making B, and delayed recognition memory for three words. The present study examined the reliability and validity of the CADi. Methods: CADi evaluations were conducted for patients with dementia, healthy subjects selected from a brain checkup system, and community-dwelling elderly people participating in health checkups. Results: CADi scores were lower for dementia patients than for healthy elderly individuals and correlated significantly with Mini-Mental State Examination scores. Cronbach’s alpha values for the CADi were acceptable (over 0.7), and test–retest reliability was confirmed via a significant correlation between scores separated by a one-year interval. Conclusion: These results suggest that the CADi is a useful tool for mass screening of dementia in Japanese populations. Keywords: dementia, mass screening, early detection, iPa

AS-2, a novel inhibitor of p53-dependent apoptosis, prevents apoptotic mitochondrial dysfunction in a transcription-independent manner and protects mice from a lethal dose of ionizing radiation

In a previous study, we reported that some tetradentate zinc(II) chelators inhibit p53 through the denaturation of its zinc-requiring structure but a chelator, Bispicen, a potent inhibitor of in vitro apopto- sis, failed to show any efficient radioprotective effect against irradiated mice because the toxicity of the chelator to mice. The unsuitability of using tetradentate chelators as radioprotectors prompted us to undertake a more extensive search for p53-inhibiting agents that are weaker zinc(II) chelators and therefore less toxic. Here, we show that an 8-hydroxyquinoline (8HQ) derivative, AS-2, suppresses p53-dependent apoptosis through a transcription-independent mechanism. A mechanistic study using cells with different p53 characteristics revealed that the suppressive effect of AS-2 on apoptosis is specifically mediated through p53. In addition, AS-2 was less effective in preventing p53-mediated transcription-dependent events than pifithrin-l (PFTl), an inhibitor of transcription-independent apoptosis by p53. Fluorescence visualization of the extranuclear distribution of AS-2 also supports that it is ineffective on the transcription-dependent pathway. Further investigations revealed that AS-2 suppressed mitochondrial apoptotic events, such as the mitochondrial release of intermembrane proteins and the loss of mitochondrial membrane potential, although AS-2 resulted in an increase in the mitochondrial translocation of p53 as opposed to the decrease of cytosolic p53, and did not affect the apoptotic interaction of p53 with Bcl-2. AS-2 also protected mice that had been exposed to a lethal dose of ionizing radiation. Our findings indicate that some types of bidentate 8HQ chelators could serve as radioprotectors with no substantial toxicity in vivo