Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus

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Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:154

Enthalten in:

Journal of pharmacological sciences - 154(2024), 4 vom: 07. März, Seite 236-245

Sprache:

Englisch

Beteiligte Personen:

Ren, Peng [VerfasserIn]
Wang, Jing-Ya [VerfasserIn]
Chen, Hong-Lei [VerfasserIn]
Wang, Yue [VerfasserIn]
Cui, Lin-Yu [VerfasserIn]
Duan, Jing-Yao [VerfasserIn]
Guo, Wen-Zhi [VerfasserIn]
Zhao, Yong-Qi [VerfasserIn]
Li, Yun-Feng [VerfasserIn]

Links:

Volltext

Themen:

σ-1 receptor
3KX376GY7L
56-12-2
Estrogens
GABA/Glutamate
Gamma-Aminobutyric Acid
Glutamic Acid
Hippocampus
Journal Article
Neurogenesis
Postpartum depression
Sigma-1 Receptor

Anmerkungen:

Date Completed 18.03.2024

Date Revised 18.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.jphs.2024.02.003

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM36975025X