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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE139428 | GEO | 2019/12/01

REPOSITORIES: GEO

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Project description:DNA microarray-based genome-wide transcriptional profiling and gene network analyses were used to characterize the molecular underpinnings of the frontal neocortical organization in rhesus macaque, with particular focus on the differences in the functional annotation of genes in the primary motor cortex and the prefrontal association cortex. Biofunctional analysis of the differentially expressed genes showed that the list of genes selectively expressed in the primary motor cortex were enriched with genes involved in development, oligodendrocyte function, and increased energy consumption, whereas the list of genes selectively expressed in the prefrontal association cortex were enriched with genes involved in cell morphology and calcium dynamics. These functional differences in selectively expressed genes may reflect the fundamental molecular structure of each cortex. Brain tissue was obtained from 4 adolescent rhesus monkeys (Macaca mulatta) aged between 2.6 and 2.7 years that had been bred in group cages without being subjected to any experimental treatment. Adequate measures were taken to minimize pain and discomfort, in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 80M-bM-^@M-^S23). The monkeys were perfused with 500M-bM-^@M-^S1000 ml of ice-cold saline containing heparin sodium (1000 U/ml, Novo Heparin; Leo Pharmaceutical Products, Ballerup, Denmark) through the ascending aorta within 15 min of an overdose injection of pentobarbital sodium (50 mg/kg, i.p., Somnopentyl; Kyoritsu Shoji, Tokyo, Japan). The 2 neocortical areas (M1 and A46) were identified by sulcal landmarks. We used the forelimb region of M1 for the present analysis, which is located around the superior genu of the central sulcus. A46 was obtained from both the upper and lower banks of the principal sulcus. Each area from the left hemispheres was dissected on crushed ice and immediately frozen in liquid nitrogen.

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

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