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B4Galnt1-knockout and cuprizone-induced demyelination is associated with changes in parvalbumin and calretinin-expressing interneurons in the murine cortex

Inhibitory interneurons are key output modulators of cortical micro-columns. Changes in expression of parvalbumin (PV) and calretinin (CR) interneurons have been observed in many neurodevelopmental and psychiatric disorders. We hypothesize that demyelination may also be associated with interneuronal phenotype changes. The study was conducted on four groups consisting of three male mice each three month old. The control group consisted of C57Bl/6 (wild-type, WT) mice, whereas other groups consisted of WT mice treated with cuprizone, B4Galnt1-knockout mice (KO), and KO treated with cuprizone. The animals were sacrificed at the age of 3 months, their brains were sampled, perfused, cryoprotected and stored at –80ºC. Immunohistochemical staining for interneuronal markers PV and CR was performed on free-floating brain sections, and quantification of immunoreactive optical density in hippocampus, caudoputamen, primary somatosensory and primary motor cortices was performed. Demyelination is associated with statistically significant reduction in PV expression and an increase in CR expression in the murine cortices. Cuprizone-induced demyelinaion is characterized by quantitative changes of the interneuronal phenotypes, but the general pattern of expression seems to be intact ; contrary to that, demyelination caused by the B4Galnt1 gene deficiency is associated with a changed PV and CR expression pattern compared to WT animals. The most profound changes are observed in the somatosenzory cortex of the KO animals, whereas their primary motor cortex seems to be unaffected. In cuprizone-fed animals, the phenotype change is most evident in the hippocampus and primary motor cortex. Demyelination might be associated with phenotype changes of the inhibitory PV and CR-expressing interneurons in the murine cortex. This is especially pronounced among the PV-expressing interneurons, a subpopulation that can be myelinated. Funding: The study has been funded by projects HRZZ IP-2014-09-2324 & VIF2015-MEFOS-21 Ethical Committee Approval: Ethical Committee of the Faculty of Medicine Osijek, classification: 602- 04/18-08/07, register number: 2158-61-07-18-19.

Interneurons ; Demyelination ; Beta-1, 4-N-Galactosaminyltransferase 1 ; Cuprizone ; Parvalbumin

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