Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)
Abstract
:1. Introduction
2. Results
2.1. Effects of pCPA and Fluoxetine on Zebrafish Behavior in the Novel Tank Diving Test
2.2. Effects of pCPA and Fluoxetine on 5-HT Metabolism in Zebrafish Brain
2.3. Effects of pCPA and Fluoxetine on mRNA Levels of Tph2, Slc6a4b, Mao, Htr1aa, Htr2aa, Creb, Bdnf, Ntrk2a and Ngfra Genes in Zebrafish Brain
2.4. Effects of pCPA and Pargyline on Zebrafish Behavior in the Novel Tank Diving Test
2.5. Effects of pCPA and Pargyline on 5-HT Metabolism in Zebrafish Brain
2.6. Effects of pCPA and Pargyline on the mRNA Levels of Tph2, Slc6a4b, Mao, Htr1aa, Htr2aa, Creb, Bdnf, Ntrk2a and Ngfra Genes in Zebrafish Brain
3. Discussion
4. Materials and Methods
4.1. Zebrafish
4.2. Drugs and Treatments
4.3. The Novel Tank Diving (NT) Test
4.4. 5-HT and 5-HIAA Concentrations Assay by HPLC
4.5. mRNA Level Assay by qPCR
4.6. Statistics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Trait | pCPA (2 mg/L) | Fluoxetine (0.2 mg/L) | Interaction |
---|---|---|---|
Distance traveled | F1,36 < 1 | F1,36 = 20.0, p < 0.001 | F1,36 = 2.3, p = 0.14 |
Distance from tank’s bottom | F1,36 = 28.0, p < 0.001 | F1,36 = 72.5, p < 0.001 | F1,36 = 10.9, p = 0.002 |
Time spent in the lower third | F1,36 = 18.4, p < 0.001 | F1,36 = 64.0, p < 0.001 | F1,36 = 8.6, p = 0.006 |
Time spent in the upper third | F1,36 = 34.1, p < 0.001 | F1,36 = 92.1, p < 0.001 | F1,36 = 21.5, p < 0.001 |
Trait | pCPA (2 mg/L) | Fluoxetine (0.2 mg/L) | Interaction |
---|---|---|---|
5-HT | F1,36 = 54.2, p < 0.001 | F1,36 = 44.2, p < 0.001 | F1,36 = 2.0, p = 0.17 |
5-HIAA | F1,36 = 6.5, p = 0.015 | F1,36 = 6.9, p = 0.013 | F1,36 = 2.1, p = 0.16 |
5-HIAA/5-HT | F1,36 = 18.4, p < 0.001 | F1,36 = 11.3, p = 0.002 | F1,36 = 12.2, p = 0.0013 |
Gene | pCPA (2 mg/L) | Fluoxetine (0.2 mg/L) | Interaction |
---|---|---|---|
Tph2 | F1,36 = 2.7, p = 0.11 | F1,36 = 27.0, p < 0.001 | F1,36 = 1.7, p = 0.20 |
Slc6a4b | F1,36 = 3.5, p < 0.07 | F1,36 = 10.9, p = 0.002 | F1,36 < 1 |
Mao | F1,36 < 1 | F1,36 = 7.8, p = 0.008 | F1,36 < 1 |
Htr1aa | F1,36 < 1 | F1,36 < 1 | F1,36 = 1.0, p = 0.32 |
Htr2aa | F1,36 < 1 | F1,36 = 12.7, p < 0.001 | F1,36 < 1 |
Creb | F1,36 < 1 | F1,36 2.6, p = 0.12 | F1,36 < 1 |
Bdnf | F1,36 = 1.9, p = 0.26 | F1,36 = 1.2, p = 0.28 | F1,36 = 1.6, p = 0.22 |
Ntrk2a | F1,36 < 1 | F1,36 = 5.9, p = 0.02 | F1,36 < 1 |
Ngfra | F1,36 = 1.2, p = 0.28 | F1,36 < 1 | F1,36 < 1 |
Trait | pCPA (2 mg/L) | Pargyline (0.5 mg/L) | Interaction |
---|---|---|---|
Distance traveled | F1,36 = 1.3, p = 0.26 | F1,36 = 23.4, p < 0.001 | F1,36 = 16.5, p < 0.001 |
Distance from tank’s bottom | F1,36 = 34.6, p < 0.001 | F1,36 = 67.1, p < 0.001 | F1,36 = 16.8, p = 0.002 |
Time spent in the lower third | F1,36 = 25.8, p < 0.001 | F1,36 = 96.4, p < 0.001 | F1,36 = 15.9, p = 0.006 |
Time spent in the upper third | F1,36 = 44.7, p < 0.001 | F1,36 = 74.5, p < 0.001 | F1,36 = 28.1, p < 0.001 |
Trait | pCPA (2 mg/L) | Pargyline (0.5 mg/L) | Interaction |
---|---|---|---|
5-HT | F1,36 = 24.3, p < 0.001 | F1,36 = 299.6, p < 0.001 | F1,36 = 6.7, p = 0.014 |
5-HIAA | F1,36 = 1.03, p = 0.32 | F1,36 = 31.0, p = 0.015 | F1,36 = 12.2, p = 0.0013 |
5-HIAA/5-HT | F1,36 < 1 | F1,36 = 57.0, p < 0.001 | F1,36 < 1 |
Gene | pCPA (2 mg/L) | Pargyline (0.5 mg/L) | Interaction |
---|---|---|---|
Tph2 | F1,36 < 1 | F1,36 = 1.6, p = 0.22 | F1,36 < 1 |
Slc6a4b | F1,36 < 1 | F1,36 = 7.0, p = 0.012 | F1,36 = 1.0, p = 0.32 |
Mao | F1,36 = 6.2, p = 0.018 | F1,36 = 1.9, p = 0.26 | F1,36 < 1 |
Htr1aa | F1,36 = 2.2, p = 0.14 | F1,36 = 19.4, p < 0.001 | F1,36 = 1.2, p = 0.28 |
Htr2aa | F1,36 = 6.2, p = 0.018 | F1,36 = 3.6, p = 0.07 | F1,36 = 1.3, p = 0.27 |
Creb | F1,36 < 1 | F1,36 = 7.9, p = 0.008 | F1,36 < 1 |
Bdnf | F1,36 = 15.6, p < 0.001 | F1,36 = 11.3, p = 0.002 | F1,36 = 1.6, p = 0.22 |
Ntrk2a | F1,36 = 1.8, p = 0.19 | F1,36 = 12.4, p < 0.001 | F1,36 < 1 |
Ngfra | F1,36 = 4.4, p = 0.042 | F1,36 = 2.4, p = 0.13 | F1,36 = 2.8, p = 0.10 |
Gene | Primer Sequences | Annealing Temperatures, °C | Amplicon Size, bp |
---|---|---|---|
Polr2eb | F5′-GTGACGCAGGATGAATTGGA-3′ R5′-CACCAGGACTGTCAGGTCATT-3′ | 62 | 105 |
Tph2 | F5′-TCTACTACAACCCTTACACGCAGA-3′ R5′-CGTCACAGACGGTGGTTAAG-3′ | 62 | 105 |
Slc6a4b | F5′-ACCGCAAATCCAATGACCGAT-3′ R5′-CGCTCACGGGAACCTCTG-3′ | 63 | 144 |
Mao | F5′-AAACCATGCACTTGATGACTGA-3′ R5′-TCATACTTGCCATACCCCCTG-3′ | 62 | 121 |
Hr1aa | F5′-GCTGCACTTCTTCCATCCTG-3′ R5′-GGTTTCCTCCAACCCAACAT-3′ | 61 | 178 |
Htr2aa | F5′-TTTGGCAGTGGTTTGTGAAC-3′ R5′-ATCCAGTGAGTGGCAGGTGT-3′ | 61 | 257 |
Creb | F5′-GCTTTGAATCGCAGACATCA-3′ R5′-ATGGCATAATCGTGGTCGTT-3′ | 60 | 409 |
Bdnf | F5′-TGCGAGTTATAGTGCCGCTT-3′ R5′-AGCCGCCGTTACTCTTTCTC-3′ | 63 | 313 |
Ntrk2a | F5′-TATTCCCTTCAGCGTGTCTGG-3′ R5′-GCATGAAATGAGCAGATACGG-3′ | 62 | 233 |
Ngfra | F5′-GATTTAGATCGTCTGTGGAGC-3′ R5′-AAAATGATGTACGCCAGGAG-3′ | 59 | 161 |
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Evsiukova, V.S.; Bazovkina, D.; Bazhenova, E.; Kulikova, E.A.; Kulikov, A.V. Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio). Int. J. Mol. Sci. 2021, 22, 12851. https://doi.org/10.3390/ijms222312851
Evsiukova VS, Bazovkina D, Bazhenova E, Kulikova EA, Kulikov AV. Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio). International Journal of Molecular Sciences. 2021; 22(23):12851. https://doi.org/10.3390/ijms222312851
Chicago/Turabian StyleEvsiukova, Valentina S., Daria Bazovkina, Ekaterina Bazhenova, Elizabeth A. Kulikova, and Alexander V. Kulikov. 2021. "Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)" International Journal of Molecular Sciences 22, no. 23: 12851. https://doi.org/10.3390/ijms222312851