Dopaminergic neuroprotective effects of rotigotine via 5-HT1A receptors: Possibly involvement of metallothionein expression in astrocytes

Astrocytes exert neuroprotective effects through production of antioxidant molecules and neurotrophic factors. A recent study showed that stimulation of astrocyte serotonin 1A (5-HT1A) receptors promotes astrocyte proliferation and upregulation of the antioxidant molecules metallothionein (MT)-1,2, which protect dopaminergic neurons against oxidative stress. Rotigotine, an anti-parkinsonian drug, can bind to dopamine and 5-HT1A receptors. In this study, we examined neuroprotective effects of rotigotine in models of Parkinson's disease and involvement of astrocyte 5-HT1A receptors in neuroprotective effects of rotigotine against dopaminergic neurodegeneration. Rotigotine increased the number of astrocytes and MT-1,2 expression in cultured astrocytes. Pretreatment with conditioned media from rotigotine-treated astrocytes significantly inhibited 6-hydroxydopamine (6-OHDA)-induced dopaminergic neurotoxicity. These effects were completely blocked by a 5-HT1A antagonist or MT-1,2 specific antibody. Subcutaneous administration of rotigotine increased MT-1,2 expression in striatal astrocytes and prevented reduction of dopaminergic neurons in the substantia nigra of a 6-OHDA-lesioned mouse model of Parkinson's disease. These effects were blocked by co-administration with a 5-HT1A antagonist. These results suggest that rotigotine exerts neuroprotective effects through upregulation of MT expression in astrocytes by targeting 5-HT1A receptors. Our findings provide a possible therapeutic application of rotigotine to prevent dopaminergic neurodegeneration in Parkinson's disease

Agropastoral economies and land use in Bronze Age Western Anatolia

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Effect of olfaction on the sensitivity of bitter taste

味覚と嗅覚の受容は異なる経路で脳へと伝達される一方、嗅覚の存在によって味の感じ方が変わることが知られているが、香気成分が味成分の受容そのものに与える影響については明確にされていない。本研究では、ラットを用いた飲水選択嗜好実験を行い、香気成分の添加により苦味溶液の選択率に変化が見れるかどうかを確認することにより、香気成分が苦味の感受性に与える影響について検討した。濃度の異なる塩酸キニーネ水溶液を用いた４瓶選択嗜好実験では、通常水群、香気水群（苦味溶液に10ppmの酪酸ブチルを添加）ともに苦味濃度が増加するほど嗜好率が低下したが、香気水群では0.001mMの苦味溶液で嗜好率が有意に増加した（p＜0.01)。一方、不快臭を示すヘキサナールを用いた場合では、個体差が大きく有意差は認められなかった。ヒトを用いた官能検査では、10ppmの酪酸ブチル、ヘキサナール、イソバレルアルデヒドのいづれの添加でも、0.01mM塩酸キニーネ水溶液の苦味を増加させた。これらの結果から、酪酸ブチルのような香気成分は苦味の感受性を変化させることが示唆され、香気成分の添加により苦味を修飾できる可能性が示された。It is known that not only taste but also olfaction (aroma) largely contributes the flavor of food, however, there is insufficient information about the interaction of olfaction and sensitivity of taste. In the present study, we investigated the effect of olfaction on the sensitivity of bitter taste by four-bottle preference test using rats. Ten male Sprague Dawley rats (6-weeks age) were divided into two groups: control and odor groups, and the drinking water of the odor group were added 10 ppm of butyl acetate (fruit-like odor). Rats were provided four bottles of drinking water containing different concentrations of quinine hydrochloride (0, 0.001, 0.01, 0.1 mM), and the preference rates were measured. The positions of the 4 bottles were randomized and switched every 48 h to avoid positional preference. During 8 days of experimental period, the volume of the 0.001 mM quinine hydrochloride consumed by the rats in the odor group was higher than that in the control group (p<0.01). In contrast, the addition of 10 ppm of 1-hexanal (off-flavor odor) had no effect on the preference rate of the 0.001 mM quinine hydrochloride by rats. Further, any addition of 10 ppm of butyl acetate, 1-hexanal, or isovaleraldehyde increased the sensitivity of bitter taste of 0.01mM quinine hydrochloride by human sensory evaluation. The results indicate that some odors such as butyl acetate may modify sensitivity of bitter taste in human and rat

The Effects of English Language Learner Classification on Students’ Educational Experience and Later Academic Achievement

English Language Learner (ELL) students are the fastest growing student population within the United States. In spite of federal and state laws and regulations that require states and local districts to provide ELLs with support services, prior research has indicated that ELL students are in general lagging behind non-ELL students in academic achievement. An unanswered question is whether and how the initial designation of students as ELL (apart from their actual skill level) may influence their later academic progress and experiences. The main purpose of this study, then, was to examine the effects of initial ELL classification (while controlling for their actual skill level) on students’ academic experiences and later academic achievement. In particular, it compared outcomes for high-scoring ELL students (just below the cutoff for being classified as Initially Fluent English Speaking, IFEP) and students just above the cutoff who were classified as IFEP. This study also investigated whether students’ particular profiles of proficiency at the time of the initial classification (speaking, listening) influenced their academic experiences and achievement, as well as the experiences and achievement of students who retained their ELL status over a long term despite having initial scores placing them near the cutoff for being classified as IFEP.This study used student-level longitudinal data (Kindergarten through tenth grade) from a very large school district in southern California. The sample consisted of 13,335 students who were near the cutoff score of the initial CELDT (administered in Kindergarten) for distinguishing ELL from Initially Fluent English Proficient (IFEP) students. Outcomes examined included standardized test scores, course grades, and whether students enrolled in gate-keeper courses (e.g., Algebra) in the normative year (e.g., 8th grade). Regression discontinuity analyses showed that for students who were near the cutoff score for ELL and IFEP classification, being initially classified as ELLs was not a disadvantage. ELLs outperformed IFEPs in English Language Arts and Mathematics in early elementary grades; this difference disappeared in later grades, and the two groups showed equivalent performance. The patterns of differences and similarities between ELLs and IFEPs did not depend on whether students were more skilled in listening or speaking.Among students who were initially near the cutoff for being classified as ELL, students who retained their ELL classification for a long term (at least five years) showed lower academic performance and developed English proficiency more slowly than students who were reclassified as IFEP in early years (before five years.) On average, students retaining their ELL classification for a long term tended to have lower initial CELDT scores, lower parent education levels, lower attendance rates in school, a higher proportion of students who were male, and a higher proportion of students who were designated as needing special education services