Antidepressive-like Behavior-Related Metabolomic Signatures of Sigma-1 Receptor Knockout Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Experimental design
2.3. Detection of Endogenous Metabolites
2.4. Voluntary Activity and Ingestion Behavior
2.5. Depression-like Behavior
2.5.1. Tail Suspension Test
2.5.2. Sucrose Preference Test
2.6. Anxiety-like Behavior
2.6.1. Zero Maze Test
2.6.2. Open-Field Test
2.7. Quantitative PCR (qPCR) Analysis
2.8. Weight of Organs
2.9. HistologyBrain Tissue Preparation for Histological Analysis
Brain Tissue Preparation for Histological Analysis
2.10. Immunohistochemistry
2.10.1. Staining of Serotonin (5-HT) and Tryptophan Hydroxylase 2 (TPH2)
2.10.2. Image Analysis
2.11. Statistical Analysis
3. Results
3.1. Age- and Genotype-Related Metabolic Signatures in Plasma and Brain Tissue of Sig1R KO Mice
3.2. Reduced Behavioral Despair in Sig1R KO Mice Is Associated with Increased Levels of Serotonin
3.3. Anxiety-like Behavior Characteristics of CD-1 Background Sig1R KO Mice
3.4. Physiological and Anatomical Characteristics of Sig1R KO Mice
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene Name | Sigmar1 | Pgrmc1 | Tph2 | Gabbr2 | Drd1 | Drd2 | Dnajc14 (Drip78) |
---|---|---|---|---|---|---|---|
Protein Name | Sigma-1 Receptor | Sigma-2 Receptor | Tryptophan 5-Hydroxylase 2 | GABA-B Receptor Subunit 2 | D(1A) Dopamine Receptor | D(2) Dopamine Receptor | Dopamine Receptor Interacting Protein |
Prefrontal cortex | - | 1 ± 0.0 | 1.1 ± 0.1 | 1.1 ± 0.1 | 0.9 ± 0.2 | 0.7 ± 0.3 | 0.7 ± 0.2 |
Striatum | - | 0.9 ± 0.1 | 1.5 ± 0.2 | 1.6 ± 0.3 | 1 ± 0.1 | 1 ± 0.2 | 1.1 ± 0.5 |
Hypothalamus | - | 1 ± 0.1 | 0.9 ± 0.2 | 1 ± 0.1 | 1.1 ± 0.2 | 1 ± 0.1 | 0.6 ± 0.1 |
Midbrain | - | 1.1 ± 0.2 | 0.8 ± 0.2 | 0.8 ± 0.1 | 1.8 ± 0.6 | 1 ± 0.1 | 1.1 ± 0.2 |
Hippocampus | - | 0.8 ± 0.1 | 1.3 ± 0.2 | 0.9 ± 0.1 | 0.9 ± 0.1 | 0.9 ± 0.1 | 0.8 ± 0.0 |
Cortex | - | 0.8 ± 0.3 | 1 ± 0.1 | 1.5 ± 0.2 * | 0.7 ± 0.2 | 0.7 ± 0.3 | 1 ± 0.2 |
Organs/Group | Organs Weights, % of Body Weight | |||
---|---|---|---|---|
4 M | 6 M | 18 M | ||
Brain | WT | 1.2 ± 0.02 | 1.2 ± 0.05 | 1.3 ± 0.02 |
Sig1R KO | 1.3 ± 0.03 * | 1.3 ± 0.08 * | 1.4 ± 0.03 * | |
Heart | WT | 0.5 ± 0.01 | 0.5 ± 0.03 | 0.5 ± 0.02 |
Sig1R KO | 0.4 ± 0.01 | 0.4 ± 0.01 * | 0.4 ± 0.05 * | |
Kidney | WT | 1.2 ± 0.05 | 1.6 ± 0.07 | 1.6 ± 0.06 |
Sig1R KO | 1.2 ± 0.03 | 1.3 ± 0.03 * | 1.3 ± 0.05 * | |
Pancreas | WT | 0.7 ± 0.07 | 1.0 ± 0.11 | 0.9 ± 0.07 |
Sig1R KO | 0.8 ± 0.06 | 0.5 ± 0.08 * | 0.6 ± 0.05 * | |
Liver | WT | 4.5 ± 0.09 | 5.2 ± 0.43 | 5.2 ± 0.33 |
Sig1R KO | 4.4 ± 0.10 | 4.8 ± 0.35 | 4.9 ± 0.35 |
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Svalbe, B.; Zvejniece, B.; Stelfa, G.; Vilks, K.; Vavers, E.; Vela, J.M.; Dambrova, M.; Zvejniece, L. Antidepressive-like Behavior-Related Metabolomic Signatures of Sigma-1 Receptor Knockout Mice. Biomedicines 2022, 10, 1572. https://doi.org/10.3390/biomedicines10071572
Svalbe B, Zvejniece B, Stelfa G, Vilks K, Vavers E, Vela JM, Dambrova M, Zvejniece L. Antidepressive-like Behavior-Related Metabolomic Signatures of Sigma-1 Receptor Knockout Mice. Biomedicines. 2022; 10(7):1572. https://doi.org/10.3390/biomedicines10071572
Chicago/Turabian StyleSvalbe, Baiba, Baiba Zvejniece, Gundega Stelfa, Karlis Vilks, Edijs Vavers, José Miguel Vela, Maija Dambrova, and Liga Zvejniece. 2022. "Antidepressive-like Behavior-Related Metabolomic Signatures of Sigma-1 Receptor Knockout Mice" Biomedicines 10, no. 7: 1572. https://doi.org/10.3390/biomedicines10071572