Alzheimer’s Disease Associated Presenilin 1 and 2 Genes Dysregulation in Neonatal Lymphocytes Following Perinatal Asphyxia
Abstract
:1. Introduction
2. Results
2.1. Expression of the Amyloid Protein Precursor Gene in Lymphocytes
2.2. Expression of the β-Secretase Gene in Lymphocytes
2.3. Expression of the Hypoxia-Inducible Factor 1-α Gene in Lymphocytes
2.4. Expression of the Presenilin 1 Gene in Lymphocytes
2.5. Expression of the Presenilin 2 Gene in Lymphocytes
3. Discussion
4. Materials and Methods
4.1. Study Setting and Design
- Newborns (full-term and preterm) > 31 weeks of gestational age,
- metabolic acidosis with pH < 7.0 (in umbilical cord or newborn blood sample obtained within 60 min after birth),
- or Base deficit (BE) > −12,
- or Apgar score of 0–5 at 10 min or continued need for resuscitation at 10 min of age,
- and presence of multiple organ-system failures,
- and clinical evidence of encephalopathy: hypotonia, abnormal oculomotor or pupillary movements, weak or absent suck, periodic breathing/apnea or clinical seizures,
- neurologic findings cannot be attributed to other cause (inborn error of metabolism, a genetic disorder, congenital neurologic disorder, medication effect).
4.2. Study Population and Sample Size
4.3. Study of Gene Expression Such as: Amyloid Protein Precursor, β-Secretase, Presenilin 1 and 2 and Hypoxia-Inducible Factor 1-α
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Martinello, K.; Hart, A.R.; Yap, S.; Mitra, S.; Robertson, N.J. Management and investigation of neonatal encephalopathy: 2017 update. Arch. Dis. Child. Fetal Neonatal Ed. 2017, 102, F346–F358. [Google Scholar] [CrossRef] [PubMed]
- Odd, D.; Heep, A.; Luyt, K.; Draycott, T. Hypoxic-ischemic brain injury: Planned delivery before intrapartum events. J. Neonatal Perinat. Med. 2017, 10, 347–353. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Locci, E.; Bazzano, G.; Demontis, R.; Chighine, A.; Fanos, V.; D’Aloja, E. Exploring Perinatal Asphyxia by Metabolomics. Metabolites 2020, 10, 141. [Google Scholar] [CrossRef] [Green Version]
- Oorschot, D.E.; Sizemore, R.J.; Amer, A.R. Treatment of Neonatal Hypoxic-Ischemic Encephalopathy with Erythropoietin Alone, and Erythropoietin Combined with Hypothermia: History, Current Status, and Future Research. Int. J. Mol. Sci. 2020, 21, 1487. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Popescu, M.R.; Panaitescu, A.M.; Pavel, B.; Zagrean, L.; Peltecu, G.; Zagrean, A.-M. Getting an Early Start in Understanding Perinatal Asphyxia Impact on the Cardiovascular System. Front. Pediatr. 2020, 8, 68. [Google Scholar] [CrossRef]
- Workineh, Y.; Semachew, A.; Ayalew, E.; Animaw, W.; Tirfie, M.; Birhanu, M. Prevalence of perinatal asphyxia in East and Central Africa: Systematic review and meta-analysis. Heliyon 2020, 6, e03793. [Google Scholar] [CrossRef]
- LaRosa, D.A.; Ellery, S.J.; Walker, D.W.; Dickinson, H. Understanding the Full Spectrum of Organ Injury Following Intrapartum Asphyxia. Front. Pediatr. 2017, 5, 16. [Google Scholar] [CrossRef] [Green Version]
- Bryce, J.; Boschi-Pinto, C.; Shibuya, K.; E Black, R. WHO estimates of the causes of death in children. Lancet 2005, 365, 1147–1152. [Google Scholar] [CrossRef]
- Albrecht, M.; Zitta, K.; Groenendaal, F.; Van Bel, F.; Peeters-Scholte, C. Neuroprotective strategies following perinatal hy-poxia-ischemia: Taking aim at NOS. Free Radic. Biol. Med. 2019, 142, 123–131. [Google Scholar] [CrossRef]
- Hakobyan, M.; Dijkman, K.P.; Zonnenberg, I.A.; Groenendaal, F.; Laroche, S.; Naulaers, G.; Rijken, M.; Steiner, K.; Van Straaten, H.L.; Swarte, R.M.; et al. Outcome of Infants with Therapeutic Hypothermia after Perinatal Asphyxia and Early-Onset Sepsis. Neonatology 2018, 115, 127–133. [Google Scholar] [CrossRef]
- Sugiura-Ogasawara, M.; Ebara, T.; Yamada, Y.; Shoji, N.; Matsuki, T.; Kano, H.; Kurihara, T.; Omori, T.; Tomizawa, M.; Miyata, M.; et al. Adverse pregnancy and perinatal outcome in patients with recurrent pregnancy loss: Multiple imputation analyses with propensity score adjustment applied to a large-scale birth cohort of the Japan Environment and Children’s Study. Am. J. Reprod. Immunol. 2018, 81, e13072. [Google Scholar] [CrossRef] [Green Version]
- Smits, A.; Annaert, P.; Van Cruchten, S.; Allegaert, K. A physiology-based pharmacokinetic framework to support drug de-velopment and dose precision during therapeutic hypothermia in neonates. Front. Pharmacol. 2020, 11, 587. [Google Scholar] [CrossRef]
- Lutz, I.C.; Allegaert, K.; De Hoon, J.N.; Marynissen, H. Pharmacokinetics during therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy: A literature review. BMJ Paediatr. Open 2020, 4, e000685. [Google Scholar] [CrossRef]
- Michniewicz, B.; Szpecht, D.; Sowińska, A.; Sibiak, R.; Szymankiewicz, M.; Gadzinowski, J. Biomarkers in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia. Child’s Nerv. Syst. 2020, 36, 2981–2988. [Google Scholar] [CrossRef]
- Solevåg, A.; Schmölzer, G.; Cheung, P.-Y. Novel interventions to reduce oxidative-stress related brain injury in neonatal asphyxia. Free. Radic. Biol. Med. 2019, 142, 113–122. [Google Scholar] [CrossRef]
- Sipos, E.; Kerenyi, A.; Orsolits, B.; Demeter, K.; Bakos, P.; Pottyondi, P.; Paszthy-Szabo, B.; Aliczki, M.; Balogh, Z.; Bhavesh, R.; et al. A translational model of moderate perinatal asphyxia reveals lasting behavioral deficits in the absence of focal neuronal loss. J. Cereb. Blood Flow Metab. 2017, 37, 470–471. [Google Scholar]
- Millar, L.J.; Shi, L.; Hoerder-Suabedissen, A.; Molnár, Z. Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges. Front. Cell. Neurosci. 2017, 11, 78. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sendeku, F.W.; Azeze, G.G.; Fenta, S.L. Perinatal asphyxia and its associated factors in Ethiopia: A systematic review and meta-analysis. BMC Pediatr. 2020, 20, 1–11. [Google Scholar] [CrossRef]
- Chavez-Valdez, R.; Emerson, P.; Goffigan-Holmes, J.; Kirkwood, A.; Martin, L.J.; Northington, F.J. Delayed injury of hippo-campal interneurons after neonatal hypoxia-ischemia and therapeutic hypothermia in a murine model. Hippocampus 2018, 28, 617–630. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Li, L.; Zhang, X.; Xie, W.; Li, L.; Yang, D.; Heng, X.; Du, Y.; Doody, R.S.; Le, W. Prenatal hypoxia may aggravate the cognitive impairment and Alzheimer’s disease neuropathology in APPSwe/PS1A246E transgenic mice. Neurobiol. Aging 2013, 34, 663–678. [Google Scholar] [CrossRef]
- Schiefecker, A.J.; Putzer, G.; Braun, P.; Martini, J.; Strapazzon, G.; Antunes, A.P.; Mulino, M.; Pinggera, D.; Glodny, B.; Brugger, H.; et al. Total TauProtein as Investigated by Cerebral Microdialysis Increases in Hypothermic Cardiac Arrest: A Pig Study. Ther. Hypothermia Temp. Manag. 2021, 11, 28–34. [Google Scholar] [CrossRef]
- Takahashi, K.; Hasegawa, S.; Maeba, S.; Fukunaga, S.; Motoyama, M.; Hamano, H.; Ichiyama, T. Serum tau protein level serves as a predictive factor for neurological prognosis in neonatal asphyxia. Brain Dev. 2014, 36, 670–675. [Google Scholar] [CrossRef] [PubMed]
- Bernert, G.; Hoeger, H.; Mosgoeller, W.; Stolzlechner, D.; Lubec, B. Neurodegeneration, Neuronal Loss, and Neurotransmitter Changes in the Adult Guinea Pig with Perinatal Asphyxia. Pediatr. Res. 2003, 54, 523–528. [Google Scholar] [CrossRef] [Green Version]
- Chavez-Valdez, R.; Lechner, C.; Emerson, P.; Northington, F.J.; Martin, L.J. Accumulation of PSA-NCAM marks nascent neurodegeneration in the dorsal hippocampus after neonatal hypoxic-ischemic brain injury in mice. Br. J. Pharmacol. 2021, 41, 1039–1057. [Google Scholar] [CrossRef]
- Pluta, R.; Ułamek-Kozioł, M.; Januszewski, S.; Czuczwar, S.J. Shared Genomic and Proteomic Contribution of Amyloid and Tau Protein Characteristic of Alzheimer’s Disease to Brain Ischemia. Int. J. Mol. Sci. 2020, 21, 3186. [Google Scholar] [CrossRef] [PubMed]
- Pluta, R.; Ułamek-Kozioł, M.; Januszewski, S.; Czuczwar, S.J. Participation of Amyloid and Tau Protein in Neuronal Death and Neurodegeneration after Brain Ischemia. Int. J. Mol. Sci. 2020, 21, 4599. [Google Scholar] [CrossRef]
- Pluta, R.; Ułamek-Kozioł, M.; Kocki, J.; Bogucki, J.; Januszewski, S.; Bogucka-Kocka, A.; Czuczwar, S.J. Expression of the tau protein and amyloid protein precursor processing genes in the CA3 area of the hippocampus in the ischemic model of Alz-heimer’s disease in the rat. Mol. Neurobiol. 2020, 57, 1281–1290. [Google Scholar] [CrossRef] [Green Version]
- Radenovic, L.; Nenadic, M.; Ułamek-Kozioł, M.; Januszewski, S.; Czuczwar, S.J.; Andjus, P.R.; Pluta, R. Heterogeneity in brain distribution of activated microglia and astrocytes in a rat ischemic model of Alzheimer’s disease after 2 years of survival. Aging 2020, 12, 12251–12267. [Google Scholar] [CrossRef] [PubMed]
- Ułamek-Kozioł, M.; Czuczwar, S.J.; Januszewski, S.; Pluta, R. Proteomic and genomic changes in tau protein, which are as-sociated with Alzheimer’s disease after ischemia-reperfusion brain injury. Int. J. Mol. Sci. 2020, 21, 892. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kiryk, A.; Pluta, R.; Figiel, I.; Mikosz, M.; Ulamek, M.; Niewiadomska, G.; Jablonski, M.; Kaczmarek, L. Transient brain ischemia due to cardiac arrest causes irreversible long-lasting cognitive injury. Behav. Brain Res. 2011, 219, 1–7. [Google Scholar] [CrossRef]
- Benterud, T.; Pankratov, L.; Solberg, R.; Bolstad, N.; Skinningsrud, A.; Baumbusch, L.; Sandvik, L.; Saugstad, O.D. Perinatal Asphyxia May Influence the Level of Beta-Amyloid (1-42) in Cerebrospinal Fluid: An Experimental Study on Newborn Pigs. PLoS ONE 2015, 10, e0140966. [Google Scholar] [CrossRef]
- Karran, E.; Mercken, M.; De Strooper, B. The amyloid cascade hypothesis for Alzheimer’s disease: An appraisal for the devel-opment of therapeutics. Nat. Rev. Drug Discov. 2011, 10, 698–712. [Google Scholar] [CrossRef] [PubMed]
- Hansson, O.; Zetterberg, H.; Vanmechelen, E.; Vanderstichele, H.; Andreasson, U.; Londos, E.; Wallin, A.; Minthon, L.; Blennow, K. Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment. Neurobiol. Aging 2010, 31, 357–367. [Google Scholar] [CrossRef]
- Liu, W.; Yang, Q.; Wei, H.; Dong, W.; Fan, Y.; Hua, Z. Prognostic Value of Clinical Tests in Neonates With Hypoxic-Ischemic Encephalopathy Treated With Therapeutic Hypothermia: A Systematic Review and Meta-Analysis. Front. Neurol. 2020, 11, 133. [Google Scholar] [CrossRef]
- Graham, E.M.; Everett, A.D.; Delpech, J.C.; Northington, F.J. Blood biomarkers for evaluation of perinatal encephalopa-thy-State of the art. Curr. Opin. Pediatr. 2018, 30, 199–203. [Google Scholar] [CrossRef] [Green Version]
- Murray, D.M. Biomarkers in neonatal hypoxic–ischemic encephalopathy—Review of the literature to date and future directions for research. Handb. Clin. Neurol. 2019, 162, 281–293. [Google Scholar] [CrossRef]
- Nataf, S.; Guillen, M.; Pays, L. Common Neurodegeneration-Associated Proteins Are Physiologically Expressed by Human B Lymphocytes and Are Interconnected via the Inflammation/Autophagy-Related Proteins TRAF6 and SQSTM1. Front. Immunol. 2019, 10, 2704. [Google Scholar] [CrossRef]
- Higgins, R.D.; Raju, T.; Edwards, A.D.; Azzopardi, D.V.; Bose, C.L.; Clark, R.H.; Ferriero, D.M.; Guillet, R.; Gunn, A.J.; Hagberg, H.; et al. Hypothermia and Other Treatment Options for Neonatal Encephalopathy: An Executive Summary of the Eunice Kennedy Shriver NICHD Workshop. J. Pediatr. 2011, 159, 851–858.e1. [Google Scholar] [CrossRef] [Green Version]
- Gaskin, F.; Finley, J.; Fang, Q.; Xu, S.; Fu, S.M. Human antibodies reactive with β-amyloid protein in Alzheimer’s disease. J. Exp. Med. 1993, 177, 1181–1186. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Monsonego, A.; Zota, V.; Karni, A.; Krieger, J.I.; Bar-Or, A.; Bitan, G.; Budson, A.E.; Sperling, R.; Selkoe, D.J.; Weiner, H.L. Increased T cell reactivity to amyloid β protein in older humans and patients with Alzheimer disease. J. Clin. Investig. 2003, 112, 415–422. [Google Scholar] [CrossRef] [Green Version]
- Feng, Y.; Liao, S.; Wei, C.; Jia, D.; Wood, K.; Liu, Q.; Wang, X.; Shi, F.-D.; Jin, W.-N. Infiltration and persistence of lymphocytes during late-stage cerebral ischemia in middle cerebral artery occlusion and photothrombotic stroke models. J. Neuroinfl. 2017, 14, 248. [Google Scholar] [CrossRef] [Green Version]
- Miró-Mur, F.; Urra, X.; Ruiz-Jaén, F.; Pedragosa, J.; Chamorro, Á.; Planas, A.M. Antigen-dependent T cell response to neural peptides after human ischemic stroke. Front. Cell Neurosci. 2020, 14, 206. [Google Scholar] [CrossRef] [PubMed]
- Wojsiat, J.; Laskowska-Kaszub, K.; Mietelska-Porowska, A.; Wojda, U. Search for Alzheimer’s disease biomarkers in blood cells: Hypotheses-driven approach. Biomark. Med. 2017, 11, 917–931. [Google Scholar] [CrossRef] [Green Version]
- Herrera-Rivero, M.; Soto-Cid, A.; Hernandez, M.E.; Aranda-Abreu, G.E. Tau, APP, NCT and BACE1 in lymphocytes through cognitively normal ageing and neuropathology. An. Acad. Bras. Ciências 2013, 85, 1489–1496. [Google Scholar] [CrossRef] [Green Version]
- Chomczynski, P.; Sacchi, N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform ex-traction. Anal. Biochem. 1987, 62, 156–159. [Google Scholar] [CrossRef]
- Kocki, J.; Ułamek-Kozioł, M.; Bogucka-Kocka, A.; Januszewski, S.; Jabłoński, M.; Gil-Kulik, P.; Brzozowska, J.; Petniak, A.; Furmaga-Jabłońska, W.; Bogucki, J.; et al. Dysregulation of amyloid precursor protein, β-secretase, presenilin 1 and 2 genes in the rat selectively vulnerable CA1 subfield of hippocampus following transient global brain ischemia. J. Alzheimers Dis. 2015, 47, 1047–1056. [Google Scholar] [CrossRef] [Green Version]
- Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real time quantitative PCR and the 2-ΔΔCT method. Methods 2001, 25, 402–408. [Google Scholar] [CrossRef]
- Sekeljic, V.; Bataveljic, D.; Stamenkovic, S.; Ułamek, M.; Jabłoński, M.; Radenovic, L.; Pluta, R.; Andjus, P.R. Cellular markers of neuroinflammation and neurogenesis after ischemic brain injury in the long-term survival rat model. Brain Struct. Funct. 2011, 217, 411–420. [Google Scholar] [CrossRef]
Group | Age (Days) | Gestational Age (Weeks) | Birth Weight (g) | Apgar Score (1 min) | RBC (×1000/µL) | WBC (/µL) | Lymphocyte (/µL) | PLT (×1000/µL) | Hct (%) | pH | BE (Mmol/L) |
---|---|---|---|---|---|---|---|---|---|---|---|
1–7 days after birth n = 8/group | |||||||||||
Control | 6 ± 1 | 39 ± 1 | 3082 ± 369 | 10.0 ± 0 | 4845 ± 184 | 12,661 ± 1133 | 6713 ± 860 | 405 ± 30 | 45 ± 1 | 7.40 ± 0.03 | 1.0 ± 0.8 |
Asphyxia | 4 ± 3 | 39 ± 2 | 3721 ± 501 | 3.4 ± 2 | 4651 ± 663 | 25,988 ± 8632 | 4541 ± 2507 | 259 ± 66 | 50 ± 8 | 7.25 ± 0.12 | −5.8 ± 5.5 |
8–14 days after birth n = 7/group | |||||||||||
Control | 12 ± 2 | 39 ± 1 | 3539 ± 723 | 9.9 ± 0.4 | 4964 ± 366 | 12,317 ±3851 | 7007 ± 1070 | 323 ± 102 | 47 ± 4 | 7.39 ± 0.03 | 1.4 ± 2.4 |
Asphyxia | 12 ± 2 | 39 ± 3 | 3153 ± 862 | 2.7 ± 2.5 | 4470 ± 462 | 20,181 ± 4016 | 6311 ± 1671 | 236 ± 35 | 46 ± 5 | 6.99 ± 0.23 | −12.2 ± 9.8 |
15+ days after birth n = 11/group | |||||||||||
Control | 20 ± 3 | 38 ± 2 | 3343 ± 558 | 9.8 ± 0.4 | 4534 ± 489 | 13,254 ± 2021 | 7129 ± 1310 | 601 ± 126 | 41 ± 4 | 7.41 ± 0.02 | 0.2 ± 1.3 |
Asphyxia | 19 ± 3 | 37 ± 3 | 2868 ± 622 | 1.6 ± 1.6 | 4385 ± 951 | 18,697 ± 8925 | 5736 ± 1429 | 230 ± 54 | 43 ± 9 | 7.13 ± 0.25 | −13.7 ± 9.1 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Tarkowska, A.; Furmaga-Jabłońska, W.; Bogucki, J.; Kocki, J.; Pluta, R. Alzheimer’s Disease Associated Presenilin 1 and 2 Genes Dysregulation in Neonatal Lymphocytes Following Perinatal Asphyxia. Int. J. Mol. Sci. 2021, 22, 5140. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105140
Tarkowska A, Furmaga-Jabłońska W, Bogucki J, Kocki J, Pluta R. Alzheimer’s Disease Associated Presenilin 1 and 2 Genes Dysregulation in Neonatal Lymphocytes Following Perinatal Asphyxia. International Journal of Molecular Sciences. 2021; 22(10):5140. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105140
Chicago/Turabian StyleTarkowska, Agata, Wanda Furmaga-Jabłońska, Jacek Bogucki, Janusz Kocki, and Ryszard Pluta. 2021. "Alzheimer’s Disease Associated Presenilin 1 and 2 Genes Dysregulation in Neonatal Lymphocytes Following Perinatal Asphyxia" International Journal of Molecular Sciences 22, no. 10: 5140. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105140