Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and subsequent motor symptoms, but various non-motor symptoms (NMS) often precede motor symptoms. Recently, NMS have attracted much attention as a clue for identifying patients in a prodromal stage of PD, which is an excellent point at which to administer disease-modifying therapies (DMTs). These prodromal symptoms include olfactory loss, constipation, and sleep disorders, especially rapid eye movement sleep behavior disorder (RBD), all of which are also important for elucidating the mechanisms of the initiation and progression of the disease. For the development of DMTs, an animal model that reproduces the prodromal stage of PD is also needed. There have been various mammalian models reported, including toxin-based, genetic, and alpha synuclein propagation models. In this article, we review the animal models that exhibit NMS as prodromal symptoms and also discuss an appropriate prodromal model and its importance for the development of DMT of PD.
The aging process is accompanied by various neurophysiological changes, and the severity of neurodegenerative disorders such as Parkinson’s disease (PD) increases with aging. However, the precise neuroanatomical changes that accompany the aging process in both normal and pathologic conditions remain unknown. This is in part because there is a lack of high-resolution imaging tool that has the capacity to image a desired volume of neurons in a high-throughput and automated manner. In the present study, focused ion beam/scanning electron microscopy (FIB/SEM) was used to image striatal neuropil in both wild-type (WT) mice and an A53T bacterial artificial chromosome (BAC) human α-synuclein (A53T-BAC-SNCA) transgenic (Tg) mouse model of PD, at 1, 3, 6, and 22 months of age. We demonstrated that spine density gradually decreases, and average spine head volume gradually increases with age in WT mice, suggesting a homeostatic balance between spine head volume and spine density. However, this inverse relationship between spine head volume and spine density was not observed in A53T-BAC-SNCATg mice. Taken together, our data suggest that PD is accompanied by an abnormality in the mechanisms that control synapse growth and maturity.
Accumulation of α-synuclein (α-syn) is the pathological hallmark of α-synucleinopathy. Rapid eye movement (REM) sleep behavior disorder (RBD) is a pivotal manifestation of α-synucleinopathy including Parkinson’s disease (PD). RBD is clinically confirmed by REM sleep without atonia (RWA) in polysomnography. To accurately characterize RWA preceding RBD and their underlying α-syn pathology, we inoculated α-syn preformed fibrils (PFFs) into the striatum of A53T human α-syn BAC transgenic (A53T BAC-SNCA Tg) mice which exhibit RBD-like phenotypes with RWA. RWA phenotypes were aggravated by PFFs-inoculation in A53T BAC-SNCA Tg mice at 1 month after inoculation, in which prominent α-syn pathology in the pedunculopontine nucleus (PPN) was observed. The intensity of RWA phenotype could be dependent on the severity of the underlying α-syn pathology.
Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) reflects neurite degeneration at the early stage of Alzheimer’s disease (AD), before extracellular Aβ aggregates are histologically detectable. Here, we demonstrate that similar changes in MARCKS occur in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) pathologies in both mouse models and human patients. The increase in the level of pSer46-MARCKS began before α-synuclein aggregate formation, at a time when human α-Syn-BAC-Tg/GBA-hetero-KO mice exhibited no symptoms, and was sustained during aging, consistent with the pattern in human postmortem brains. The results strongly imply a common mechanism of pre-aggregation neurite degeneration in AD and PD/DLB pathologies.
Objectives: This study aimed to explore how Japanese medical students are influenced by their dialogue with the general public as part of the process of professional identity formation. These findings are expected to provide insights into supporting the development of professional identity from diverse perspectives, particularly for medical students in the pre-stage of legitimate peripheral participation and those currently engaged in it. Methods: Semi-structured interviews were conducted with three medical students of different backgrounds. These students participated in a dialogue-based event with the general public, in which they ran a booth focused on medical education. A qualitative descriptive approach was adopted and an interpretivist study was conducted through a thematic analysis. Data were analyzed using the Steps for Coding and Theorization (SCAT) qualitative data analysis method. Results: The students reflected on their dialogue with the general public about medical education and discussed infrequent opportunities to recognize or disclose their professional identity in daily life. A preclinical student (third-year) noted, “I felt like I shared a similar sense of amazement with the visitors” and “It’s obvious, but I really came to realize that I’m seen from the perspective of a medical student or a healthcare professional.” In contrast, a clinical student (fifth-year) reflected, “Sharing my feelings about whether I’ve been helping others during my clinical training felt closely tied to me—there wasn’t much of a gap.” SCAT analysis revealed that preclinical students emphasized ‘reaffirming their professional identity through empathetic understanding,’ while clinical students focused on ‘disclosing their professional identity, leading to its integration with their personal identity.’. Conclusion: Dialogue with the general public unexpectedly enhanced medical students’ awareness of their professional identity. In the process of professional identity formation, dialogue with the general public can support the traditionally emphasized socialization process through participation in professional groups, particularly by facilitating the reaffirming of professional identity and its integration with personal identity.
Background: The integration of traditional and complementary medicine (T&CM) into modern medical education remains a global challenge. Kampo medicine, a Japanese traditional pharmacotherapy, is recognized in the International Classification of Diseases, 11th Revision , and is widely used; however, no structured methodology exists for efficiently designing curricula within limited time and resources. To address this gap, this study proposes a methodological framework—illustrated through Kampo medicine but generalizable to other forms of T&CM—for organizing and visualizing curricular content to guide educational needs assessment and curriculum design. Objective: The objective of this study was to develop and illustrate a reproducible mapping framework that integrates (1) real-world clinical utilization frequency and (2) the accumulation of biomedical evidence to inform educational prioritization and stepwise curriculum design for T&CM, using Kampo medicine as an exemplar. Methods: A mapping approach was developed based on two perspectives: frequency of use in clinical training and level of biomedical evidence. Twelve years of outpatient prescription data from Kyoto University Hospital were analyzed to identify the most frequently prescribed Kampo formulas. For the 10 most common formulas, PubMed searches were conducted to determine the number of randomized controlled trials. Data were integrated using hierarchical clustering and plotted along frequency–evidence axes to produce an educational priority map, which informed a stepwise curriculum design grounded in adult learning theory. Results: Prescription heat maps revealed substantial interdepartmental variation, and clustering identified distinct groups of formulas based on usage patterns. No statistically significant correlation was observed between prescription frequency and level of evidence (Pearson r =0.228, 95% CI −0.469 to 0.750; P =.53; Spearman ρ=0.498, 95% CI −0.308 to 0.926; P =.14). Integrating these two perspectives enabled interpretation of real-world prescription patterns and supported a transparent educational prioritization framework. Conclusions: This study presents a feasible and adaptable framework that links real-world clinical data with biomedical evidence to inform curriculum design in T&CM. Rather than prescribing specific content, the framework offers visual decision-making tools that align educational priorities with institutional practice patterns and can be readily adapted to complementary, alternative, and integrative medicine programs internationally.