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

Mukesh Kumar Varshney, Nancy Yiu Lin Yu, Shintaro Katayama, Xin Li, Tianyao Liu, Wan Fu Wu, Virpi Töhönen, Kaarel Krjutškov, Juha Kere, Xiaotang Fan, José Inzunza, Jan Åke Gustafsson, Ivan Nalvarte

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)27-44
Number of pages18
JournalNeuroendocrinology
Volume111
Issue number1-2
DOIs
StatePublished - Dec 2020

Keywords

  • Estrogen
  • Estrogen receptor beta
  • Locomotor activity
  • Motor cortex
  • Myelination

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Motor Function Deficits in the Estrogen Receptor Beta Knockout Mouse: Role on Excitatory Neurotransmission and Myelination in the Motor Cortex'. Together they form a unique fingerprint.

Cite this