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. 2021 May 13;22(10):5140.
doi: 10.3390/ijms22105140.

Alzheimer's Disease Associated Presenilin 1 and 2 Genes Dysregulation in Neonatal Lymphocytes Following Perinatal Asphyxia

Agata Tarkowska  1 , Wanda Furmaga-Jabłońska  1 , Jacek Bogucki  2 , Janusz Kocki  3 , Ryszard Pluta  4
Affiliations

Alzheimer's Disease Associated Presenilin 1 and 2 Genes Dysregulation in Neonatal Lymphocytes Following Perinatal Asphyxia

Agata Tarkowska et al. Int J Mol Sci. .

Abstract

Perinatal asphyxia is mainly a brain disease leading to the development of neurodegeneration, in which a number of peripheral lesions have been identified; however, little is known about the expression of key genes involved in amyloid production by peripheral cells, such as lymphocytes, during the development of hypoxic-ischemic encephalopathy. We analyzed the gene expression of the amyloid protein precursor, β-secretase, presenilin 1 and 2 and hypoxia-inducible factor 1-α by RT-PCR in the lymphocytes of post-asphyxia and control neonates. In all examined periods after asphyxia, decreased expression of the genes of the amyloid protein precursor, β-secretase and hypoxia-inducible factor 1-α was noted in lymphocytes. Conversely, expression of presenilin 1 and 2 genes decreased on days 1-7 and 8-14 but increased after survival for more than 15 days. We believe that the expression of presenilin genes in lymphocytes could be a potential biomarker to determine the severity of the post-asphyxia neurodegeneration or to identify the underlying factors for brain neurodegeneration and get information about the time they occurred. This appears to be the first worldwide data on the role of the presenilin 1 and 2 genes associated with Alzheimer's disease in the dysregulation of neonatal lymphocytes after perinatal asphyxia.

Keywords: Alzheimer’s disease; amyloid protein precursor; brain ischemia; genes; hypoxia-inducible factor 1-α; hypoxic-ischemic encephalopathy; lymphocytes; perinatal asphyxia; presenilin 1 and 2; β-secretase.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Mean levels of amyloid protein precursor (APP) gene expression in lymphocytes after perinatal asphyxia in age groups 1–7 (n = 8), 8–14 (n = 7) and 15+ (n = 8) days. Marked SD, standard deviation. N, number of children in the group. The changes between the groups were not statistically significant (Kruskal-Wallis test). (B) Mean levels of β-secretase (BACE1) gene expression in lymphocytes after perinatal asphyxia in age groups 1–7 (n = 8), 8–14 (n = 7) and 15+ (n = 8) days. Marked SD, standard deviation. N, number of children in the group. The changes between the groups were not statistically significant (Kruskal-Wallis test). (C). Mean levels of hypoxia-inducible factor 1-α (HIF1A) gene expression in lymphocytes after perinatal asphyxia in age groups 1–7 (n = 8), 8–14 (n = 7) and 15+ (n = 9) days. Marked SD, standard deviation. N, number of children in the group. The changes between the groups were not statistically significant (Kruskal-Wallis test).
Figure 2
Figure 2
(A). Mean levels of presenilin 1 (PSEN1) gene expression in lymphocytes after perinatal asphyxia in age groups 1–7 (n = 8), 8–14 (n = 7) and 15+ (n = 10) days. Marked SD, standard deviation. N, number of children in the group. The changes between the 1–7 and 8–14 day groups were not statistically significant. The indicated statistically significant differences in the level of gene expression between groups 1–7 and 15+ days (z = 3.903, p = 0.0002) and between 8–14 and 15+ days (z = 3.092, p = 0.0059) after perinatal asphyxia (Kruskal-Wallis Test). * p ≤ 0.01. (B). Mean levels of presenilin 2 (PSEN2) gene expression in lymphocytes after perinatal asphyxia in age groups 1–7 (n = 8), 8–14 (n = 7) and 15+ (n = 10) days. Marked SD, standard deviation. N, number of children in the group. The changes between the 1–7 and 8–14 day groups were not statistically significant. The indicated statistically significant differences in the level of gene expression between groups 1–7 and 15+ days (z = 3.634, p = 0.0008) and between 8–14 and 15+ days (z = 3.387, p = 0.002) after perinatal asphyxia (Kruskal-Wallis Test). * p ≤ 0.01.
Figure 3
Figure 3
Sample MRI images one of the studied patient from group 15+ T1 (A,B), DWI (C) and ADC (D) after neonatal asphyxia. Generalized atrophy of the cortex with widening of the fluid space mainly in the occipital area. Features of generalized encephalomalacia with the presence of small fluid spaces. The picture of the brain structures corresponds to hypoxic-ischemic changes.
See this image and copyright information in PMC

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