Project ID NS-MH2024_62


Co Supervisor 1A Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Department of Basic & Clinical NeuroscienceWebsite

Co Supervisor 1B Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Department of NeuroimagingWebsite

Linking maternal stress during gestation to resilience vs susceptibility in the offspring: a pre-clinical imaging study

This project will be embedded within an on-going EU funded study (“HappyMums”), which seeks to improve our understanding about biological causes of depression during pregnancy, how it impacts the offspring, and the efficacy of interventions. The study encompasses both clinical research as well as ‘reverse-translation’ into animal models.

Whilst clinical and epidemiological research in humans, also used in this project, offers valuable information regarding maternal wellbeing during pregnancy and neurodevelopmental outcomes in the offspring, this is limited in its ability to uncover causal pathogenic mechanisms. The proof of causality can instead be better achieved using animal models, which are able to model both stress during gestation and the ensuing depressive-like symptoms that occur before and continue during pregnancy. This project will employ three relevant rodent models meeting these criteria, which will be assessed via a combination of neuroimaging and post-mortem histology to achieve these three specific aims:

Year 1 – Aim (1) Identify brain biomarkers associated with depressive-like behaviour in pregnant dams

Year 2 – Aim (2) Characterise brain development in the offspring in relation to behavioural outcome (susceptibility vs resilience?)

Year 3 – Aim (3) Measure impacts of therapeutic intervention in the most relevant model, on these biomarkers.

The project will provide training and skills in the analysis of structural magnetic resonance imaging (MRI) data (neuroanatomy and diffusion tensor imaging). Specifically, the student will apply both univariate methods to look for common and distinct effects across models, but also multivariate approaches to integrate MRI data with behavioural measures and publicly available gene expression and connectivity data for the mouse brain from the Allen Brain Institute. In addition, the student will gain training in post-mortem histology and microscopy to link MRI signal changes to their underlying cellular mechanisms. The student will also be fully involved in the grant consortium, attending bi-annual progress meetings (Milan, Italy) to share data and updates, providing excellent opportunities for networking and professional development.

Representative Publications

Preclinical animal models of mental illnesses to translate findings from the bench to the bedside: Molecular brain mechanisms and peripheral biomarkers associated to early life stress or immune challenges. Cattane N, Vernon AC et al. European Neuropsychopharmacology. 2022; doi: 10.1016/j.euroneuro.2022.02.002

Behavioral, neuroanatomical, and molecular correlates of resilience and susceptibility to maternal immune activation. Mueller FS et al. Molecular Psychiatry. 2021; doi: 10.1038/s41380-020-00952-8.

Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure. Bruce MR et al. Molecular Psychiatry. 2023. doi: 10.1038/s41380-023-02020-3

Lopes JB, et al. (2023) Individual behavioral trajectories shape whole-brain connectivity in mice. Elife 12.

Brusini I et al. (2022) MRI-derived brain age as a biomarker of ageing in rats: validation using a healthy lifestyle intervention. Neurobiology of Ageing 109: 204-2015.

Walker SE, et al (2018) Alterations in brain microstructure in rats that develop abnormal aggression following peripubertal stress. Eur J Neurosci 1.