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Objective Conventional methods for organotypic hippocampal tissue slice culture (OHSC) have shown several disadvantages or limitations regarding age of animals used, duration of culture and difficulty using neurodegenerative models. Therefore, we tried to establish OHSC from old 3xTg-Alzheimer’s disease (AD) mice for longer period (over 4 weeks) and to validate utility of this system as a valid platform for translational neuroscience of AD. Methods OHSC was performed with old 3xTg-AD mice (12–14 months), old wild type mice (12–14 months) and young 3xTg-AD mice (2–4 months) using serum-free medium for 4 weeks. Hippocampal structure was evaluated by 4’, 6-diamidino-2-phenylindole (DAPI) intensity and neuronal metabolism was measured by Alamarblue assay. Pathologic characteristics of AD were also investigated; β-amyloid levels by ELISA, amyloid plaque deposition by Thioflavin-S staining, and glial activation by immunohistochemistry. Results Following 4-week culture in serum-free media, hippocampal cells and layers were well preserved in cultured slices from old AD mice as was in those from young AD and old wild type mice. On the contrary, excessive regression of total visible cells was observed in conventional serum-containing medium regardless of genotype of mice. In parallel with this well preserved structure, major pathologic characteristics of AD were also well manifested in hippocampal slices from old AD mice. Conclusion Our findings suggest that long-term OHSC from old 3xTg-AD mouse can serve as a promising ex vivo system for studies on pathophysiology of AD, especially with the minimum number of sacrifice of experimental animals.

Virtual reality (VR) neuropsychological tests have emerged as a method to explore drug effects in real-life contexts in attention deficit hyperactivity disorder (ADHD) children. Functional near-infrared spectroscopy (fNIRS) is a useful tool to measure brain activity during VR tasks in ADHD children with motor restlessness. The present study aimed to explore the acute effects of methylphenidate (MPH) on behavioral performance and brain activity during a VR-based working memory task simulating real-life classroom settings in ADHD children. In total, 23 children with ADHD performed a VR n-back task before and 2 h after MPH administration concurrent with measurements of oxygenated hemoglobin signal changes with fNIRS. Altogether, 12 healthy control (HC) subjects participated in the same task but did not receive MPH treatment. Reaction time (RT) was shortened after MPH treatment in the 1-back condition, but changes in brain activation were not observed. In the 2-back condition, activation of the left dorsolateral prefrontal cortex (DLPFC) and bilateral medial prefrontal cortex (mPFC) was decreased alongside behavioral changes such as shorter RT, lower RT variability, and higher accuracy after MPH administration. Bilateral mPFC activation in the 2-back condition inversely correlated with task accuracy in the pre-MPH condition; this inverse correlation was not observed after MPH administration. In ADHD children, deactivation of the default mode network mediated by mPFC reduced during high working memory load, which was restored through MPH treatment. Our results suggest that the combination of VR classroom tasks and fNIRS examination makes it easy to assess drug effects on brain activity in ADHD children in settings simulating real-life.