ABSTRACT
Increasing evidence shows that metabolic abnormalities in body fluids are distinguishing features of the pathophysiology of Parkinson's disease. However, a non-invasive approach has not been established in the earliest or pre-symptomatic phases. Here, we report comprehensive double-cohort analyses of the metabolome using capillary electrophoresis/liquid chromatography mass-spectrometry. The plasma analyses identified 18 Parkinson's disease-specific metabolites and revealed decreased levels of seven long-chain acylcarnitines in two Parkinson's disease cohorts (n = 109, 145) compared with controls (n = 32, 45), respectively. Furthermore, statistically significant decreases in five long-chain acylcarnitines were detected in Hoehn and Yahr stage I. Likewise, decreased levels of acylcarnitine(16:0), a decreased ratio of acylcarnitine(16:0) to fatty acid(16:0), and an increased index of carnitine palmitoyltransferase 1 were identified in Hoehn and Yahr stage I of both cohorts, suggesting of initial ß-oxidation suppression. Receiver operating characteristic curves produced using 12-14 long-chain acylcarnitines provided a large area of under the curve, high specificity and moderate sensitivity for diagnosing Parkinson's disease. Our data demonstrate that a primary decrement of mitochondrial ß-oxidation and that 12-14 long-chain acylcarnitines decreases would be promising diagnostic biomarkers for Parkinson's disease.
Subject(s)
Carnitine/analogs & derivatives , Oxidation-Reduction , Parkinson Disease/diagnosis , Parkinson Disease/metabolism , Aged , Biomarkers , Carnitine/metabolism , Cohort Studies , Fatty Acids/metabolism , Female , Humans , Male , Metabolome , Metabolomics/methods , Middle Aged , Mitochondria/metabolism , Models, Biological , Muscle, Skeletal/metabolism , ROC Curve , Severity of Illness IndexABSTRACT
Some words are sound-symbolic in that they involve a non-arbitrary relationship between sound and meaning. Here, we report that 25-month-old children are sensitive to cross-linguistically valid sound-symbolic matches in the domain of action and that this sound symbolism facilitates verb learning in young children. We constructed a set of novel sound-symbolic verbs whose sounds were judged to match certain actions better than others, as confirmed by adult Japanese- as well as English speakers, and by 2- and 3-year-old Japanese-speaking children. These sound-symbolic verbs, together with other novel non-sound-symbolic verbs, were used in a verb learning task with 3-year-old Japanese children. In line with the previous literature, 3-year-olds could not generalize the meaning of novel non-sound-symbolic verbs on the basis of the sameness of action. However, 3-year-olds could correctly generalize the meaning of novel sound-symbolic verbs. These results suggest that iconic scaffolding by means of sound symbolism plays an important role in early verb learning.
