Lactoferrin Induces Erythropoietin Synthesis and Rescues Cognitive Functions in the Offspring of Rats Subjected to Prenatal Hypoxia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents
2.2. Animals
2.3. Model of Prenatal Normobaric Hypoxia
2.4. Collection of Milk Samples
2.5. Western Blotting
2.6. Novel Object Recognition Test (NOR Test)
2.7. Working Memory Analysis in the Eight-Arm Radial Maze
2.8. Statistical Analysis
3. Results
3.1. Lactoferrin-Induced Upregulation of EPO in Pregnant Rats and Their Pups
3.2. Effect of apo-rhLF Injections to Pregnant and Lactating Rats on the Memory of Their Offspring
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Rat Groups (N) | Substance Injected | Biochemical Tests | Behavioral Tests |
---|---|---|---|
Control with saline | Saline (0.5 mL; E9, 11, 13, 15) | 2 females and 10 embryos (E14); WB-EPO | NOR (P22, n = 17 and P90, n = 15) 8 arm-maze, (P90, n = 7) |
Hypoxia (E14) with saline | Saline (0.5 mL; E9, 11, 13, 15) | 2 females and 16 embryos (E14); WB-EPO 4 females and 11 pups (P14); WB: EPO, HIF1α and HIF2α | NOR (P22, n = 17 and P90, n = 15) 8 arm-maze, (P90, n = 7) |
Hypoxia (E14) with apo-rhLF during gestation—Hyp+LF1 | Apo-rhLF (10 mg in 0.5 mL of saline; E9, E11, E13, E15) | 2 females and 12 embryos (E14); WB: EPO | NOR (P22, n = 15 and P90, n = 7) 8 arm-maze, (P90, n = 7) |
Hypoxia (E14) with apo-rhLF during lactation—Hyp+LF2 | Apo-rhLF (10 mg in 0.5 mL of saline; daily from P0 to P15 days after birth) | 4 females and 16 pups (P14); WB: EPO, HIF1α and HIF2α | NOR (P22, n = 17 and P90, n = 7) 8 arm-maze, (P90, n = 7) |
Control with apo-rhLF during lactation | Apo-rhLF (10 mg in 0.5 mL of saline; daily from P0 to P15 days after birth) | 3 females and 9 pups (P14); WB: EPO, HIF1α and HIF2α; | |
Control with apo-rhLF during lactation | Apo-rhLF (single injection 10 mg in 0.5 mL of saline on P14) | 3 females and 6 pups (P14) WB: LF in dam milk and in the pup gastric content |
Groups | Analyzed Part of Pregnant Rats or Fetus | ||||
---|---|---|---|---|---|
Brain of Pregnant Females | Placenta | Brain of the Embryos | Torso of the Embryos | ||
Embryos (n = 10) from control pregnant rats (n = 2) with i.p. saline injections during gestation | EPO presence | 0 | 0 | 0 | 0 |
EPO absence | 2 | 10 | 10 | 10 | |
Embryos (n = 16) from pregnant rats (n = 2) with hypoxia and i.p. saline injections during gestation | EPO presence | 0 | 0 | 0 | 0 |
EPO absence | 2 | 16 | 16 | 16 | |
Embryos (n = 12) from pregnant rats (n = 2) with hypoxia and i.p. apo-rhLF injections during gestation | EPO presence | 2 | 0 | 12 | 12 |
EPO absence | 0 | 12 | 0 | 0 |
Organ | Pups (n = 9) of Control Rats with i.p. apo-rhLF Injections during Lactation (n = 3) | Pups (n = 11)of Rats after Hypoxia and i.p. Saline Injections during Lactation (n = 4) | Pups (n = 16)of Rats after Hypoxia and i.p. apo-rhLF Injections during Lactation (n = 4) | |||
---|---|---|---|---|---|---|
HIF1α HIF2α and EPO Presence | HIF1α HIF2α and EPO Absence | HIF1α HIF2α and EPO Presence | HIF1α HIF2α and EPO Absence | HIF1α HIF2α and EPO Presence | HIF1α HIF2α and EPO Absence | |
Brain | 9 | 0 | 0 | 11 | 16 | 0 |
Liver | 9 | 0 | 0 | 11 | 16 | 0 |
Spleen | 9 | 0 | 0 | 11 | 16 | 0 |
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Sokolov, A.V.; Dubrovskaya, N.M.; Kostevich, V.A.; Vasilev, D.S.; Voynova, I.V.; Zakharova, E.T.; Runova, O.L.; Semak, I.V.; Budevich, A.I.; Nalivaeva, N.N.; et al. Lactoferrin Induces Erythropoietin Synthesis and Rescues Cognitive Functions in the Offspring of Rats Subjected to Prenatal Hypoxia. Nutrients 2022, 14, 1399. https://doi.org/10.3390/nu14071399
Sokolov AV, Dubrovskaya NM, Kostevich VA, Vasilev DS, Voynova IV, Zakharova ET, Runova OL, Semak IV, Budevich AI, Nalivaeva NN, et al. Lactoferrin Induces Erythropoietin Synthesis and Rescues Cognitive Functions in the Offspring of Rats Subjected to Prenatal Hypoxia. Nutrients. 2022; 14(7):1399. https://doi.org/10.3390/nu14071399
Chicago/Turabian StyleSokolov, Alexey V., Nadezhda M. Dubrovskaya, Valeria A. Kostevich, Dmitrii S. Vasilev, Irina V. Voynova, Elena T. Zakharova, Olga L. Runova, Igor V. Semak, Alexander I. Budevich, Natalia N. Nalivaeva, and et al. 2022. "Lactoferrin Induces Erythropoietin Synthesis and Rescues Cognitive Functions in the Offspring of Rats Subjected to Prenatal Hypoxia" Nutrients 14, no. 7: 1399. https://doi.org/10.3390/nu14071399
APA StyleSokolov, A. V., Dubrovskaya, N. M., Kostevich, V. A., Vasilev, D. S., Voynova, I. V., Zakharova, E. T., Runova, O. L., Semak, I. V., Budevich, A. I., Nalivaeva, N. N., & Vasilyev, V. B. (2022). Lactoferrin Induces Erythropoietin Synthesis and Rescues Cognitive Functions in the Offspring of Rats Subjected to Prenatal Hypoxia. Nutrients, 14(7), 1399. https://doi.org/10.3390/nu14071399