Gene expression analysis of motor cortex between BERKO and wild type mouse

Introduction: Male estrogen receptor beta (ERβ) knockout (BERKO) mice display anxiety and aggression linked to, among others, altered serotonergic signaling in the basolateral amygdala and dorsal raphe, impaired cortical radial glia migration and reduced GABAergic signaling. Effects on primary motor cortex (M1 cortex) and locomotor activity as a consequence of ERβ loss have not been investigated. Objective: The aim of this study was to determine whether locomotor activity is altered as a consequence of the changes in the M1 cortex. Methods: Locomotor activity of WT and BERKO male mice was evaluated using the open-field and rotarod tests. Molecular changes in the M1 cortex were analyzed by RNA-sequencing, electron microscopy, electrophysiology, and immunofluorescence techniques. In addition, we established oligodendrocyte cultures from WT and BERKO mouse embryonic stem cells to evaluate oligodendrocyte function. Results: Locomotor profiling revealed that BERKO mice were more active than WT mice but had impaired motor coordination. Analysis of the M1 cortex pointed out differences in synapse function and myelination. There was a reduction in GABAergic signaling resulting in imbalanced excitatory and inhibitory neurotransmission, as well as a defective oligodendrocyte differentiation accompanied by myelin defects. The effects of loss of ERβ on oligodendrocyte differentiation was confirmed in vitro. Conclusion: ERβ is an important regulator of GABAergic interneurons and oligodendrocyte differentiation, which impacts on adult M1 cortex function, and may be linked to increased locomotor activity and decreased motor coordination in BERKO mice. mRNA extracted from M1 cortex of 6 WT and 6 BERKO mice were multiplexed and sequenced using Illumina Hiseq 2000 in 3 lanes (2 samples from each cortex in 3 technical replicates). 1 BERKO sample was removed due to being an outlier.