Mouse models of immune dysfunction: their neuroanatomical differences reflect their anxiety-behavioural phenotype

Journal article

Acute lymphoblastic leukemia (ALL), the most common childhood cancer, has a survival rate of 90%. However, due to the impact of chemotherapy on the central nervous system (CNS), survivors are at risk for long-term cognitive deficits. Previous studies demonstrate that methotrexate (MTX), a cornerstone of ALL chemotherapy, is linked to cognitive deficits. Our research also demonstrates that after MTX treatment during early life, adult mice may exhibit smaller volumes in some brain regions as assessed by MRI. Interleukin 6 (IL-6), an inflammatory cytokine, is elevated in the blood, brain, liver, and gut following MTX exposure in rodent models and has been implicated in cognitive deficits and neuroinflammation. Here, I present longitudinal in vivo magnetic resonance imaging (MRI) findings in a mouse model to examine the impact of MTX on brain development from early life to adulthood and explore the role of IL-6 using genetically modified Il6-knockout mice. I present results showing that MTX treatment at postnatal day 17 (P17) and 19 (P19), causes brain volume changes evident at 4 weeks (P28) which return to baseline by 9 weeks of age (P63). The impact of IL-6 in this model displayed sex-specific effects on MRI measured brain volume.M.Sc

Authors: Fernandes, DJ; Spring, S; Corre, C; Tu, A; Qiu, LR

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: Molecular Psychiatry
• Volume: 27
• Issue: 7
• Pages: 3047-3055
• Publication date: 2022-04-14
• DOI: 10.1038/s41380-022-01535-5
• EISSN: 1476-5578
• ISSN: 1359-4184
• Language: English
• Keywords: Immune system; Phenotype; Neuroanatomy; Brain size; Endophenotype; Magnetic resonance imaging; Multiple sclerosis; Medicine; Genetics; Immunology; Corpus callosum; Biology; Thalamus; Gene; Neuroscience; Psychology