メンタルヘルス、認知、ストレス、パフォーマンスに関する研究プラットフォーム
受託サービス、共同研究・提携のご提案
Pre-clinical model for Brain Health, Neuroinflammation and Aging Research
(脳の健康、神経炎症,、および老化研究のための非臨床研究モデル)
● Proprietary TNO mouse strain: LDLR-/-, Leiden mice
> Established model for obesity, MASLD/MASH, CVD (94% C57BL6 and 6% 129S background)
> Human-like pathology and human-like molecular mechanisms.
> Head-to-head: model mimics most important patient subgroups.
(Alvarez-Arranz et al, Hepatology, 2022)
>> Call for Collaboration; Brain Health PPP
Neurodegeneration, Astrogliosis, Neurodegeneration
Publication:
□ Obesity accelerates age-related memory deficits and affects brain connectivity and white matter tract integrity in Ldlr-/-.Leiden mice.
□ Exercise Partly Protects Against Semaglutide-Induced Muscle Loss in Obese Ldlr-/-.Leiden Mice.
● Functional and Molecular Readout;
> Behaviour & cognition tests during natural aging
> Mitochondrial dysfunction assay (FGF21, GDF15)
> Histopathology: morphology & protein expression and distribution
> Brain: transcriptomics, oxylipins, multiplex neuroinflammation
panel; oxidative stress
● Advanced imaging;in collaboration with Radboudumc
> Brain structure (e.g. grey matter and white matter integrity)
> Brain function (connectivity analysis, cerebral blood flow)
> Polarized light imaging
● Atherosclerosis induced via Autonomous Nerveous System
> Nervous system (Fight and Flight Branch = Sympathetic)
> Neuroimmune cardiovascular interfaces control atherosclerosis
Gut-Liver-Brain Axis Research to Improve Metabolic Health "GLoBAL"
(腸肝脳相関研究プロジェクト)
● Overview;
Investigation of Gut-Liver-Brain Axis in severe obese patients undergoing bariatric surgery(~n=150) with extensive characterization of tissue biopsies and systems biology.
Extensive neuroimaging (MRI), cognition tests, plasma and microbiota analysis over time (pre-operation, hospitalization and post-operation).
● Readout and Samples;
> Brain; Cognition, Behaviour test, Brain fMRI scan
> Samples (n=500)
> Tissue; Liver, Adipose tissue, Jejunam.
> Plasma; Lipidomics, Adipokine, Hepatokines, Bile acids, etc.
> Microbiota; Feces, Mucosal swab; Stomach, Jejunam
● Tests conducted;
> NeuroPhysiological test; MoCA, COWAT, IQ, Working memory, Episodic memory, TAP.
> Behaviour; Scores of Impulsivity, Motivation, Depression, GI complaint, etc
> GI complaints (e.g. GSRS and IBS-SSS scores) to evaluate diarrhea, obstipation and others
● Invitation to analyse specific health aspect using the samples in stock as the followings;
> Liver (histology, transcriptomics)
> Visceral adipose tissues
> Jejunum, gut permeability
> Mucosal & feces microbiota
> Plasma
> SCFA, amino acids, lipids, bile acids, Vitamins, etc
● Opportunities to assess relation between MB and Brain
> Choose interaction of interest (e.g. microbiota to long-term memory, or gut permeability to cognition tests)
> Use available data or eventually measure additional parameters
> Check for correlations or associations
> Identify critical body parameters that correlate with brain health
Publication:
□ The long-term effect of metabolic bariatric surgery on innate immune cell phenotype and function Int J Obes Aug 2025.
van Tuijl J, Vreeken D, Broeders W, Cossins B, van Emst L, Seidel F, Stienstra R, Li Y, Joosten LAB, Netea MG, Hazebroek EJ, Kleemann R, Kiliaan AJ, Bekkering S, Riksen NP.
□ Gastrointestinal complaints after Roux-en-Y gastric bypass surgery. Impact of microbiota and its metabolites. Helyon Nov, 2024.
Emma Custers, Yonta G.R. van der Burgh, Debby Vreeken, Frank Schuren, Tim J. van den Broek, Lars Verschuren, Ivo de Blaauw, Mark Bouwens, Robert Kleemann, Amanda J. Kiliaan, Eric J. Hazebroek.
ストレス性認知機能障害誘発モデルによるヒト臨床試験
● 概要;
メンタルヘルス、認知、ストレス、パフォーマンスを評価指標とする脳と身体の相関研究向けユニークなヒューマンインターフェース
> 試験期間;~2週間
> 対象:医薬品、栄養素、ライフスタイル、社会的心理要因等
> 目的:認知機能、覚醒度、メンタルヘルス等の改善度評価
> Subject: 主に健常者(リクルート対象者、例数、年齢層応相談)
●テストオプション例;
> 覚醒テスト: Psychomotor Vigilance Test; Attention/Alertness
> 作業記憶: Working Memory Task; Reasoning and Decision making
> 認知柔軟性: Cognitive Flexibility Task; Adaptation, Task switching
> 注意ネットワーク:Attention Network test; Alertness, Orientation
> 情動抑制:Affective Stroop Task; Processing of Emotional info
> ドライビングシミュレーターテスト;Driving simulator test
●測定項目:例;
> 脳:EEG, fNIRS(functional Near-Infrared Spectroscopy)
> 目:瞳孔サイズ、まばたき、視線追跡
> 血液:サイトカイン、コルチゾール、代謝性疾患・炎症マーカー
> 心:ECG、HRV (Heart rate variability)
> 腸内細菌叢、腸内細菌叢による代謝物
> ウエアラブルディバイス: Daily monitoring, EMA, ESM
> 反応時間、正確さ、認知能力
> 皮膚コンダクタンス、覚醒度、姿勢
> 質問票による調査
●ストレス;治験参加者への負荷オプション例(応相談);
> 認知負荷、ノイズ、冷水、室温変化、気圧変化
> 睡眠不足、情緒的ストレス、社会的ストレス
> 低レベル電気刺激、有酸素運動、障害物コース
●共同研究テーマ:例;
> 新規予測アルゴリズム開発:
パフォーマンスの急激な低下に対する早期アラートシステム
> 認知能力と注意力を向上させる新規治療法の特定
> 睡眠不足改善に有効な新規治療法 (例:サプリメント) の特定
● Publication
Seven robust and easy to obtain biomarkers to measure acute stress.
Brain Behavior and Immunity - Health, July 2024

