Effects of perinatal asphyxia on the expression of the acylethanolamide/endocannabinoid signaling system in the hippocampus and dorsal striatum of postweaned rats

GALEANO, PABLO; BLANCO CALVO, EDUARDO; HOLUBIEC, MARIANA INÉS; ROMERO, JUAN IGNACIO; LOGICA TORNATORE, TAMARA; SUARÉZ, JUAN; PAVON, FRANCISCO JAVIER; CAPANI, FRANCISCO; RODRÍGUEZ DE FONSECA, FERNANDO

Oviedo

Congreso; 1st International Congress of Psychobiology; 2015

Universidad de Oviedo

Introduction. Perinatal asphyxia (PA) is an obstetric complication caused by oxygen deprivation (hypoxia) or a reduced blood flow (ischemia) to different body organs, including the central nervous system (CNS). Within the CNS, the hippocampus and the striatum are particularly vulnerable areas to PA. Nowadays, PA is considered as one of the principal causes of morbimortality in term and pre-term neonates, and is associated with an increased likelihood of suffering from cerebral palsy, mental retardation, learning disabilities, ADHD, among others. The endocannabinoid system (ENC) is a lipid transmitter system involved in a variety of physiological processes including appetite, pain, synaptic plasticity, memory and mood regulation. The ENC has recently received growing attention as having potential neuroprotective functions in some neurological disorders. On the other hand, ethanolamides are closely related to the ENC. For instance, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) act directly and indirectly on endocannabinoid receptors and it has been reported that both have neuroprotective functions. In addition, one of the common targets of both ethanolamides is the nuclear peroxisome proliferator activated receptor alpha (PPAR-alpha). Objective. We aim to analyze the changes produced by PA in the ENC and in some ethanolamine compounds in the hippocampus and dorsal striatum using a murine model of PA. Experimental procedures. PA was induced by immersing foetuses-containing uterine horns, removed from ready-to-deliver rats, into a water bath for 19 min (perinatally asphyxiated rats, PA rats). Spontaneous (CTL) and caesarean-delivered pups (C+) were used as controls. At one month of age, animals were transcardially perfused, brains were post-fixed and cut into coronal sections (30 mm thick). Next, immunohistochemistry, cell counting and densitometry procedures for NeuN, GFAP, Iba1, DAGLalpha, NAPE-PLD, CB1, PPARalpha and FAAH were performed in hippocampus and dorsal striatum. Results. In PA rats, neuronal loss was observed in CA1 and CA3 regions of the hippocampus, while astrogliosis was detected in the CA1 area in C+ and PA rats. These results indicate that PA rats show damage in the hippocampus, as previously described. NAPE-PLD and PPARalpha were decreased in hippocampal areas (CA1, CA3 and dentate gyrus) and dorsal striatum in PA rats. Finally, it was found that FAAH was increased in the hippocampus and dorsal striatum of C+ rats. Conclusions. Since NAPE-PLD is an enzyme that participates in the chemical process that converts lipids into OEA, and the latter is a PPARalpha agonist, these results support the use of OEA as a potential neuroprotective compound in PA. Finally, due to the fact that FAAH was only increased in C+ animals, it could be seen as a sensitive biomarker of some processes that take place during cesarean delivery.