Investigating neurometabolic patterns using magnetic resonance spectroscopy in the SHANK3 mouse model of autism spectrum disorder.
Channelle Tham
Donders Institute and RadboudUMC
Research on human phenotyping has broadened our knowledge of the genetic foundations of neurodevelopmental disorders, notably autism spectrum disorder. However, moving beyond correlations in human cohorts presents difficulties. In this study, we examine neurometabolic differences linked to autism using the SHANK3 mouse model. We use proton (1H) magnetic resonance spectroscopy to track neurochemical alterations in the transgenic mouse models. This non-invasive method measures the concentrations of in vivo neurometabolites.
We acquired single voxel PRESS scans in homologous brain areas—the cingulate cortex and thalamus—across three genotypes: SHANK3+/+ (wildtype), SHANK3-/+ (heterozygous), and SHANK3-/- (knockout homozygous). We imaged mixed-sex mice during adolescence (30 days post-natal) or early adulthood (70 days post-natal) using a Bruker BioSpec 11.7T scanner. We processed all spectral data using Spectroscopy Analysis Tools (SPANT), with rigorous quality control measures and visual inspection by two analysts. We compared metabolite concentrations using effect size analysis with unpaired Hedge’s g, examining how genotype affects metabolite levels in wild-type, heterozygous, and homozygous mice.
- To document region-specific neurometabolic differences associated with the SHANK3 mouse model
- To examine the downstream metabolic consequences caused by Shank3 disruptions
- To bridge the gap between preclinical findings and human phenotyping
- Channelle Tham (Animal data analysis)
- Alejandro Rivera-Olvera (Animal data acquisition)
- Sabrina van Heukelum (Animal data acquisition)
- Andor Veltien (Lab technician/hardware)
- Judith Homberg (Supervision)
- Joanes Grandjean (Daily supervision)
Clarke, W. T., Bell, T. K., Emir, U. E., Mikkelsen, M., Oeltzschner, G., Shamaei, A., Soher, B. J., & Wilson, M. (2022). NIfTI-MRS: A standard data format for magnetic resonance spectroscopy. Magnetic Resonance in Medicine. https://doi.org/10.1002/mrm.29418
Wilson, M. (2021). spant: An R package for magnetic resonance spectroscopy Analysis. Journal of Open Source Software, 6(67), 3646 https://doi.org/10.21105/joss.03646
https://doi.org/10.17605/OSF.IO/JKB6TThe following are notable deviations from the planned methodology:
- We excluded human autism and Phelan-McDermid syndrome cohort data from the study due to data acquisition issues at LEAP facilities.
- Due to time constraints, we scanned and processed 92 of the planned 120 mice.
- Lastly, we refined the name for voxels of interest from the prefrontal cortex to the anterior cingulate cortex.