Motor Function Deficits in the Estrogen Receptor Beta Knockout Mouse : Role on Excitatory Neurotransmission and Myelination in the Motor Cortex

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Varshney , M K , Yu , N Y-L , Katayama , S , Li , X , Liu , T , Wu , W-F , Tohonen , V , Krjutskov , K , Kere , J , Fan , X , Inzunza , J , Gustafsson , J-A & Nalvarte , I 2020 , ' Motor Function Deficits in the Estrogen Receptor Beta Knockout Mouse : Role on Excitatory Neurotransmission and Myelination in the Motor Cortex ' , Neuroendocrinology : international journal for basic and clinical studies on neuroendocrine relationships , vol. 111 , no. 1-2 , pp. 27-44 . https://doi.org/10.1159/000506162

Title: Motor Function Deficits in the Estrogen Receptor Beta Knockout Mouse : Role on Excitatory Neurotransmission and Myelination in the Motor Cortex
Author: Varshney, Mukesh Kumar; Yu, Nancy Yiu-Lin; Katayama, Shintaro; Li, Xin; Liu, Tianyao; Wu, Wan-Fu; Tohonen, Virpi; Krjutskov, Kaarel; Kere, Juha; Fan, Xiaotang; Inzunza, Jose; Gustafsson, Jan-Ake; Nalvarte, Ivan
Contributor: University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
Date: 2020-12
Language: eng
Number of pages: 18
Belongs to series: Neuroendocrinology : international journal for basic and clinical studies on neuroendocrine relationships
ISSN: 0028-3835
URI: http://hdl.handle.net/10138/324538
Abstract: Background: Male estrogen receptor beta (ER beta) 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 ER beta 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 ER beta loss on OL differentiation were confirmed in vitro. Conclusion: ER beta 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.
Subject: Estrogen
Estrogen receptor beta
Locomotor activity
Motor cortex
Myelination
SINGLE-CELL TRANSCRIPTOME
ER-BETA
DIFFERENTIAL EXPRESSION
NONSELECTIVE ATTENTION
SYNAPTIC PLASTICITY
NITRIC-OXIDE
ADULT
MICE
HIPPOCAMPUS
NEURONS
3121 Internal medicine
3112 Neurosciences
3124 Neurology and psychiatry
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