Brain microstructural changes in mice persist in adulthood and are modulated by the palmitoyl acyltransferase ZDHHC7

For a long time, mice have been classified as adults with completely mature brains at 8 weeks of age, but recent research suggests that developmental brain changes occur for up to 6 months. In particular, adolescence coincides with dramatic changes of neuronal structure and function in the brain that influence the connectivity between areas like hippocampus and medial prefrontal cortex (mPFC). Neuronal development and plasticity are regulated in part by the palmitoyl acyltransferase ZDHHC7, which modulates structural connectivity between hippocampus and mPFC. The aim of the current study was to investigate whether developmental changes take place in hippocampus and mPFC microstructure even after 8 weeks of age and whether deficiency of ZDHHC7 impacts such age-dependent alterations. Altogether, 46 mice at 11, 14 or 17 weeks of age with a genetic Zdhhc7 knockout (KO) or wild type (WT) were analysed with neuroimaging and diffusion tensor-based fibre tractography. The hippocampus and mPFC regions were compared regarding fibre metrics, supplemented by volumetric and immunohistological analyses of the hippocampus. In WT animals, we identified age-dependent changes in hippocampal fibre lengths that followed a U-shaped pattern, whereas in mPFC, changes were linear. In Zdhhc7-deficient animals, the fibre statistics were reduced in both regions, whereas the hippocampus volume and the intensities of myelin and neurofilament were higher in 11-week-old KO mice compared to WTs. Our results confirmed ongoing changes of microstructure in mice up to 17 weeks old and demonstrate that deleting the Zdhhc7 gene impairs fibre development, suggesting that palmitoylation is important in this process.