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

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.

Melatonin: A Potential Candidate for the Treatment of Experimental and Clinical Perinatal Asphyxia

“…There is increasing evidence that the neuropathology induced in the neonate’s brain during and after perinatal asphyxia is similar to that of adult neurodegenerative diseases, such as Alzheimer’s disease [ 13 , 42 , 44 , 45 , 46 , 49 ]. Additionally, one study found elevated plasma levels of tau protein following asphyxia on days 3 and 7 after birth [ 48 ].…”

“…Additionally, it has been noticed that newborns after perinatal asphyxia, untreated or treated with hypothermia, presented identical changes in gene expression related to the processing of the amyloid protein precursor in lymphocytes [ 49 ]. Knowing about the possibility of passing lymphocytes after perinatal asphyxia to the brain, our data suggest an additional role of lymphocytes in progressive neurodegeneration with amyloid deposition, despite hypothermic treatment of neonates after perinatal asphyxia.…”

“…It is now known that brain neurodegeneration after asphyxia is caused by numerous proteomic and genomic changes that lead to neuronal death by necrosis and apoptosis, with progressive neuroinflammation and brain atrophy, eventually leading to dementia in some cases [ 13 , 19 , 21 , 45 , 46 , 49 ]. Research indicates that perinatal asphyxia is associated with changes in amyloid and tau protein similar to alterations in Alzheimer’s disease [ 13 , 19 , 21 , 45 , 46 , 49 ]. The development of neuroinflammatory processes has been shown to play a key role in the progression of brain neurodegeneration after perinatal asphyxia [ 32 ].…”

“…The development of neuroinflammatory processes has been shown to play a key role in the progression of brain neurodegeneration after perinatal asphyxia [ 32 ]. Amyloid production and accumulation, tau protein modification and autophagy are involved in neurodegeneration after asphyxia in the same way as in Alzheimer’s disease [ 13 , 19 , 21 , 46 , 49 ]. Recirculation of blood in the brain after perinatal asphyxia and asphyxia alone provoke a violent reaction of reactive oxygen species, triggering a neuroinflammatory response and oxidative injury [ 32 ].…”

Neonatal asphyxia – predicting its occurrence and neurodevelopment of children after hypothermia treatment in the context of machine learning models – literature review

“…In addition, it is assumed that hypoxia in the perinatal period may be a factor triggering the development of Alzheimer's disease in adulthood [5]. Studies have shown changes in the expression of the presenilin 1 and 2 and amyloid protein precursor and β-secretase genes in neonates after asphyxia, similar to those observed in Alzheimer's disease [6].…”