Mukesh Kumar Varshney1, Nancy Yiu-Lin Yu1, Shintaro Katayama1, Xin Li2, Tianyao Liu2, Wan-Fu Wu3, Virpi Töhönen1,4, Kaarel Krjutškov1,5,6, Juha Kere1,6, Xiaotang Fan2, José Inzunza1, Jan-Åke Gustafsson1,3,4, Ivan Nalvarte7. 1. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. 2. Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, China. 3. Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas, USA. 4. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 5. Competence Center on Health Technologies, Tartu, Estonia. 6. Folkhälsan Research Institute, Helsinki, and Stem Cells and Metabolism Research Program, University of Helsinki, Helsinki, Finland. 7. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden, ivan.nalvarte@ki.se.
Abstract
BACKGROUND: 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. The 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: The locomotor activity of male wild-type (WT) and BERKO 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 immunohistological techniques. In addition, we established oligodendrocyte (OL) cultures from WT and BERKO mouse embryonic stem cells to evaluate OL 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 OL differentiation accompanied by myelin defects. The effects of ERβ loss on OL differentiation were confirmed in vitro. CONCLUSION: ERβ is an important regulator of GABAergic interneurons and OL differentiation, which impacts on adult M1 cortex function and may be linked to increased locomotor activity and decreased motor coordination in BERKO mice.
BACKGROUND: 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. The 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: The locomotor activity of male wild-type (WT) and BERKO 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 immunohistological techniques. In addition, we established oligodendrocyte (OL) cultures from WT and BERKO mouse embryonic stem cells to evaluate OL 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 OL differentiation accompanied by myelin defects. The effects of ERβ loss on OL differentiation were confirmed in vitro. CONCLUSION: ERβ is an important regulator of GABAergic interneurons and OL differentiation, which impacts on adult M1 cortex function and may be linked to increased locomotor activity and decreased motor coordination in BERKO mice.
Authors: Rafaela Faustino Lacerda de Souza; Thatiane Maria Almeida Silveira Mendes; Luana Adalice Borges de Araujo Lima; Daniel Soares Brandão; Diego Andrés Laplagne; Maria Bernardete Cordeiro de Sousa Journal: Front Hum Neurosci Date: 2022-05-04 Impact factor: 3.473