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. 2022 Jun 7;11(12):3263.
doi: 10.3390/jcm11123263.

Hypothermia after Perinatal Asphyxia Does Not Affect Genes Responsible for Amyloid Production in Neonatal Peripheral Lymphocytes

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

Hypothermia after Perinatal Asphyxia Does Not Affect Genes Responsible for Amyloid Production in Neonatal Peripheral Lymphocytes

Agata Tarkowska et al. J Clin Med. .

Abstract

In this study, the expression of the genes of the amyloid protein precursor, β-secretase, presenilin 1 and 2 by RT-PCR in the lymphocytes of newborns after perinatal asphyxia and perinatal asphyxia treated with hypothermia was analyzed at the age of 15-21 days. The relative quantification of Alzheimer's-disease-related genes was first performed by comparing the peripheral lymphocytes of non-asphyxia control versus those with asphyxia or asphyxia with hypothermia. In the newborns who had perinatal asphyxia, the peripheral lymphocytes presented a decreased expression of the amyloid protein precursor and β-secretase genes. On the other hand, the expression of the presenilin 1 and 2 genes increased in the studied group. The expression of the studied genes in the asphyxia group treated with hypothermia had an identical pattern of changes that were not statistically significant to the asphyxia group. This suggests that the expression of the genes involved in the metabolism of the amyloid protein precursor in the peripheral lymphocytes may be a biomarker of progressive pathological processes in the brain after asphyxia that are not affected by hypothermia. These are the first data in the world showing the role of hypothermia in the gene changes associated with Alzheimer's disease in the peripheral lymphocytes of newborns after asphyxia.

Keywords: Alzheimer’s disease; amyloid protein precursor; brain ischemia; genes; hypothermia; 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
Changes of amyloid protein precursor (APP), β-secretase (BACE1) and hypoxia-inducible factor 1-α (HIF1A) genes after perinatal asphyxia. (A) Mean levels of 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 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 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) [3].
Figure 2
Figure 2
Changes of presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes after perinatal asphyxia. (A). Mean levels of 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 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. [3].
Figure 3
Figure 3
Mean levels of amyloid protein precursor (APP), β-secretase (BACE1), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) gene expression in peripheral lymphocytes after perinatal asphyxia (A) and perinatal asphyxia with hypothermia (A + H) with survival of more than 15 days. Marked SD, standard deviation. The changes between the groups were not statistically significant (Mann-Whitney test).
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Grants and funding

The authors acknowledge the financial support from the following institutions: the Medical University of Lublin, Lublin, Poland (DS 403-WFJ and DS 222-JK), and the Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland (T3-RP).

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