The effects of fetal and perinatal asphyxia on neuronal cytokine levels and ceramide metabolism in adulthood.
In a rat model of global fetal and perinatal asphyxia, we investigated if asphyxia and long-lasting brain tolerance to asphyxia (preconditioning) are mediated by modifications in inflammatory cytokines and ceramide metabolism genes in prefrontal cortex, hippocampus and caudate-putamen at the age of 8months. Most significant changes were found in prefrontal cortex, with reduced LAG1 homolog ceramide synthase 1 expression after both types of asphyxia. Additionally, sphingosine kinase 1 was upregulated in those animals that experienced the combination of fetal and perinatal asphyxia (preconditioning), suggesting increased cell proliferation. While cytokine levels are normal, levels of ceramide genes were modulated both after fetal and perinatal asphyxia in the adult prefrontal cortex. Moreover, the combination of two subsequent asphyctic insults provides long-lasting neuroprotection in the prefrontal cortex probably by maintaining normal apoptosis and promoting cell proliferation. Better understanding of the effects of asphyxia on ceramide metabolism will help to understand the changes leading to brain tolerance and will open opportunities for the development of new neuroprotective therapies.
Department of Neuropsychology - Division Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht 6200MD, The Netherlands.
Evi
E
Vlassaks
Antonio W D
AW
Gavilanes
Johan S H
JS
Vles
Sarah
S
Deville
Boris W
BW
Kramer
Eveline
E
Strackx
Pilar
P
Martinez-Martinez
D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000378:metabolism*; D001238:Asphyxia Neonatorum / Q000235:genetics / Q000378:metabolism; D002518:Ceramides / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005311:Fetal Hypoxia / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002518:Ceramides; D016207:Cytokines