TY - JOUR
T1 - Mouse models of immune dysfunction
T2 - their neuroanatomical differences reflect their anxiety-behavioural phenotype
AU - Fernandes, Darren J.
AU - Spring, Shoshana
AU - Corre, Christina
AU - Tu, Andrew
AU - Qiu, Lily R.
AU - Hammill, Christopher
AU - Vousden, Dulcie A.
AU - Spencer Noakes, T. Leigh
AU - Nieman, Brian J.
AU - Bowdish, Dawn M.E.
AU - Foster, Jane A.
AU - Palmert, Mark R.
AU - Lerch, Jason P.
N1 - Funding Information:
This work was supported by grants from the Canadian Institutes of Health Research as well as the Province of Ontario’s Neurodevelopmental Disorders (POND) network of the Ontario Brain Institute. Additional funding support was provided by the National Science and Engineering Research Council postgraduate scholarship (DJF), The Hospital for Sick Children Restracomp Fellowship and Ontario Graduate Scholarship (DAV).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/7
Y1 - 2022/7
N2 - Extensive evidence supports the role of the immune system in modulating brain function and behaviour. However, past studies have revealed striking heterogeneity in behavioural phenotypes produced from immune system dysfunction. Using magnetic resonance imaging, we studied the neuroanatomical differences among 11 distinct genetically modified mouse lines (n = 371), each deficient in a different element of the immune system. We found a significant and heterogeneous effect of immune dysfunction on the brains of both male and female mice. However, by imaging the whole brain and using Bayesian hierarchical modelling, we were able to identify patterns within the heterogeneous phenotype. Certain structures—such as the corpus callosum, midbrain, and thalamus—were more likely to be affected by immune dysfunction. A notable brain–behaviour relationship was identified with neuroanatomy endophenotypes across mouse models clustering according to anxiety-like behaviour phenotypes reported in literature, such as altered volume in brains regions associated with promoting fear response (e.g., the lateral septum and cerebellum). Interestingly, genes with preferential spatial expression in the most commonly affected regions are also associated with multiple sclerosis and other immune-mediated diseases. In total, our data suggest that the immune system modulates anxiety behaviour through well-established brain networks.
AB - Extensive evidence supports the role of the immune system in modulating brain function and behaviour. However, past studies have revealed striking heterogeneity in behavioural phenotypes produced from immune system dysfunction. Using magnetic resonance imaging, we studied the neuroanatomical differences among 11 distinct genetically modified mouse lines (n = 371), each deficient in a different element of the immune system. We found a significant and heterogeneous effect of immune dysfunction on the brains of both male and female mice. However, by imaging the whole brain and using Bayesian hierarchical modelling, we were able to identify patterns within the heterogeneous phenotype. Certain structures—such as the corpus callosum, midbrain, and thalamus—were more likely to be affected by immune dysfunction. A notable brain–behaviour relationship was identified with neuroanatomy endophenotypes across mouse models clustering according to anxiety-like behaviour phenotypes reported in literature, such as altered volume in brains regions associated with promoting fear response (e.g., the lateral septum and cerebellum). Interestingly, genes with preferential spatial expression in the most commonly affected regions are also associated with multiple sclerosis and other immune-mediated diseases. In total, our data suggest that the immune system modulates anxiety behaviour through well-established brain networks.
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U2 - 10.1038/s41380-022-01535-5
DO - 10.1038/s41380-022-01535-5
M3 - Article
C2 - 35422470
AN - SCOPUS:85128018921
SN - 1359-4184
VL - 27
SP - 3047
EP - 3055
JO - Molecular psychiatry
JF - Molecular psychiatry
IS - 7
ER -