INTERACTION PLATFORM FOR MENTAL HEALTH, COGNITION, STRESS AND PERFORMANCE
CONTRACT SERVICE, TECHNOLOGIES OPEN FOR PARTNERING
Pre-clinical model for Brain Health, Neuroinflammation and Aging Research
● 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
AI BRAIN PATHOLOGY : Brain AI
TNO's AI histopathology algorithms turns brain sections into objective, region-level read-outs of neurodegeneration and neuroinflammation.
Quantify brain sections faster and more accurately with AI
Our AI reads whole-slide images of stained brain sections, segments the brain regions, and then detects individual cells. The result is a reproducible quantification that removes reader variability and scales to large preclinical cohorts.
Multi marker readouts
Neuron detection and density (NeuN)
Every NeuN+ neuron is detected and counted within its region, giving objective neuronal-density and neuron-loss read-outs. With more than 30k neurons per slice, such a measurement would be infeasible by hand.
Microglial activation (Iba1)
Iba1+ microglia are detected across the section to quantify microglial activation and the regional spread of neuroinflammation.
Cortical thickness
The AI-segmented cortex is measured directly into reproducible cortical-thickness maps across the whole section, a structural read-out infeasible to produce by hand at scale.
Why it matters
● Faster and cost-saving: shorter turnaround than manual scoring of large cohorts.
● Replicates the pathologist: counts cells and estimates affected tissue the way an expert scores it.
● Reads 100% of the section: densities and areas computed over the whole tissue, not a sampled subset.
● Markers beyond manual review: per-region cell counts and densities that are infeasible by hand.
● Standardized and reproducible: removes inter- and intra-reader variability.
Gut-Liver-Brain Axis Research to Improve Metabolic Health, "GLoBAL" (ongoing project, Open for partnering)
● 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
> Analysis over time, e.g. microbiota traits that predispose a person to develop GI pain complaints.
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.
Human Body Brain Interaction Platform; Model of Stress-induced Cognition Impairment
● Overview；Unique Body-Brain Technology for mental health, cognition, stress, performance, wellbeing
to investigate the efficacy (or adverse effect) of various types of test product or factor such as medicine, nutrient, lifestyle, and psycho-social.
> Rapid (2W) human studies to test interventions
> Subject; Healthy volunteer
●Test option；
> Psychomotor Vigilance Test; Attention/Alertness
> Working Memory Task; Reasoning and Decision making
> Cognitive Flexibility Task; Adaptation, Task switching
> Attention Network test; Alertness, Orientation
> Affective Stroop Task; Processing of Emotional info
> Driving simulator test
●Measures；
> Brain：EEG, fNIRS(functional Near-Infrared Spectroscopy)
> Eye：Pupil size, Blink, Eye tracking
> Blood：Cytokines, Cortisol, Metabolic, Inflammation markers
> Heart：ECG, HRV (Heart rate variability)
> Microbiota, Microbiota Metabolite
> Wearable device: Daily monitoring, EMA, ESM
> Reaction time, Acuracy, Cognitive performance
> Skin conductance, Arousal, Body Posture, Activity
> Questionnaire
●Stressors ;
> Cognitive load, Noise, Cold water, Climate chamber
> Sleep deprivation, Emotional stress, Social stress
> Mild electric shock, Hypoberic room
> Aerobic exercise, Obstacle course
●Opportunities
> Novel prediction algorithms (e.g., early alert systems warn for acute lapses in performance)
> Identify novel treatments to increase cognitive performance and alertness
> Identify novel treatments (e.g. supplements) that help to cope with little sleep
● Publication
Seven robust and easy to obtain biomarkers to measure acute stress.
Brain Behavior and Immunity - Health, July 2024
