Abstract
Perinatal asphyxia (PA) is an obstetric complication that strongly affects the CNS. The endocannabinoid system (ECS) is a lipid transmitter system involved in several physiological processes including synaptic plasticity, neurogenesis, memory, and mood. Endocannabinoids, and other acylethanolamides (AEs) without endocannabinoid activity, have recently received growing attention due to their potential neuroprotective functions in neurological disorders, including cerebral ischemia. In the present study, we aimed to analyze the changes produced by PA in the major metabolic enzymes and receptors of the ECS/AEs in the hippocampus using a rodent model of PA. To induce PA, we removed uterine horns from ready-to-deliver rats and immersed them into a water bath during 19 min. Animals delivered spontaneously or by cesarean section were employed as controls. At 1 month of age, cognitive functions were assessed and immunohistochemical procedures were carried out to determine the expression of NeuN and glial fibrillary acidic protein, enzymes responsible for synthesis (DAGLα and NAPE-PLD) and degradation (FAAH) of ECS/AEs and their receptors (CB1 and PPARα) in the hippocampus. Postweaned asphyctic rats showed impaired recognition and spatial reference memory that were accompanied by hippocampal astrogliosis and changes in the expression of enzymes and receptors. The most remarkable findings in asphyctic rats were a decrease in the expression of NAPE-PLD and PPARα in both hippocampal areas CA1 and CA3. In addition, postweaned cesarean delivery rats showed an increase in the immunolabeling for FAAH in the hippocampal CA3 area. Since, NAPE-PLD and PPARα are proteins that participate in the biochemical process of AEs, specially the neuroprotective oleoylethanolamide, these results suggest that PA dysregulates this system. These data encourage conducting future studies using AEs as potential neuroprotective compounds in animal models of PA.
Highlights
Perinatal asphyxia (PA) is an obstetric complication that can be triggered by different events, such as fetus lungs malfunction and alterations in the gas exchange in the placenta, leading to lack of oxygen or a reduced blood flow to different body organs during the perinatal period (Carrera, 2006)
We studied the expression of DAGLα, NAPE-PLD, cannabinoid receptor type 1 (CB1), PPARα, and fatty acid amide hydrolase (FAAH) in control (CTL), cesarean delivery (C+) and asphyctic (PA) 30-days-old rats
These results indicated that PA rats explored both objects, i.e., the novel and the familiar, a similar amount of time during the choice trial, and it could be concluded that recognition memory was impaired in this group of rats
Summary
Perinatal asphyxia (PA) is an obstetric complication that can be triggered by different events, such as fetus lungs malfunction and alterations in the gas exchange in the placenta, leading to lack of oxygen (hypoxia) or a reduced blood flow (ischemia) to different body organs during the perinatal period (Carrera, 2006). Bjelke’s model is a well-established PA model that has been extensively employed by our and other groups (Chen et al, 1995; Capani et al, 1997, 2001, 2003, 2009; Brake et al, 2000; Boksa and El-Khodor, 2003; Weitzdoerfer et al, 2004; Cebral et al, 2006; Wakuda et al, 2008; Morales et al, 2010; Saraceno et al, 2010, 2012; Strackx et al, 2010) Using this model, it has been observed that during this stage of development, PA may cause damage in several regions of the CNS, such as hippocampus, cerebellum, striatum, cerebral cortex, and substantia nigra (Bjelke et al, 1991; Capani et al, 2009; Campanille et al, 2015). When the circulation of the umbilical cord is altered (Capani et al, 2009); (b) it affects the whole body, mimicking global asphyxia which is the most frequent type of PA (Lubec et al, 1997; Loidl et al, 2000; Strackx et al, 2010); (c) it does not require surgical procedures which could add confounding effects; (d) both cerebral hemispheres and deep brain structures are affected by hypoxia-ischemia
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