ePoster

SPOT THE DIFFERENCE: WHOLE-BRAIN CLEARING AND MULTICHANNEL IMAGING TO MAP SEX-DEPENDENT BRAIN CELL DIFFERENCES IN MOUSE MODELS OF AUTISM SPECTRUM DISORDER

Moritz Negwerand 4 co-authors

Donders Center for Brain, Cognition and Behaviour

FENS Forum 2026 (2026)
Barcelona, Spain
Board PS07-10AM-208

Presentation

Date TBA

Board: PS07-10AM-208

Poster preview

SPOT THE DIFFERENCE: WHOLE-BRAIN CLEARING AND MULTICHANNEL IMAGING TO MAP SEX-DEPENDENT BRAIN CELL DIFFERENCES IN MOUSE MODELS OF AUTISM SPECTRUM DISORDER poster preview

Event Information

Poster Board

PS07-10AM-208

Abstract

Autism Spectrum Disorder (ASD) has been viewed as a strongly gendered with boys being diagnosed more often (3.5:1 boys:girls) and earlier (4 years vs 6 years) than girls. Whether this is due to sex-specific differences in patient presentation, diagnostic bias, or sex-specific neurodevelopmental vulnerabilities is currently unknown. We investigate the latter hypothesis and screen for sex-specific neurodevelopmental vulnerabilities in mouse models of ASD, using a four-way female/male/wildtype/mutant comparison across several mouse lines (Ehmt1 and Pten mutants for syndromic ASD, as well as BTBR mice for idiopathic ASD).
Speficially, we take an unbiased whole-brain screening approach, with multichannel staining based on the INSIHGT protocol. We label every single Parvalbumin-positive neuron, Iba1-positive microglia, and WFA-positive perineuronal net, along with a near-infrared nuclear counterstain. We then clear the brains and image them with a light-sheet microscope, and detect the labelled cells in four channels using the DELiVR pipeline, customized for every channel with training data generated in virtual reality (VR).
As a result, we get the precise coordinates of every labelled cells, as well as the general density of all cells via the nuclear counterstain. We present here our end-to-end pipeline, optimalization steps for a reproducible and scalable operation, as well as preliminary results from the first batches of brains. We are actively encouraging other groups that work with mouse models of ASD to collaborate and send us a cohort of their brains as well, so that we can get a broader view of 3D cytoarchitecture across as many mouse lines as possible.

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