Acylethanolamides and endocannabinoid signaling system in dorsal striatum of rats exposed to perinatal asphyxia

Abstract

Endocannabinoids (eCBs) and acylethanolamides (AEs) have lately received more attention due to their neuroprotective functions in neurological disorders. Here we analyze the alterations induced by perinatal asphyxia (PA) in the main metabolic enzymes and receptors of the eCBs/AEs in the dorsal striatum of rats. To induce PA, we used a model developed by Bjelke et al. (1991). Immunohistochemical techniques were carried out to determine the expression of neuronal and glial markers (NeuN and GFAP), eCBs/AEs synthesis and degradation enzymes (DAGLα, NAPE-PLD and FAAH) and their receptors (CB1 and PPARα). We found a decrease in NAPE-PLD and PPARα expression. Since NAPE-PLD and PPARα take part in the production and reception of biochemical actions of AEs, such as oleoylethanolamide, these results may suggest that PA plays a key role in the regulation of this system. These data agree with previous results obtained in the hippocampus and encourage us to develop further studies using AEs as potential neuroprotective compounds.

Palmitoylethanolamide Ameliorates Hippocampal Damage and Behavioral Dysfunction After Perinatal Asphyxia in the Immature Rat Brain

“…Although PEA endogenous content tends to increase around P30 in physiological conditions (Lee et al, 2013 ), a dysregulation of NAEs signaling system is induced by PA at this time point (Blanco et al, 2015 ; Holubiec et al, 2017 ). One month after PA, the expression of enzymes responsible for synthesis (diacylglycerol lipase-α–DAGL-α, and N -acyl-phosphatidylethanolamine-NAPE-hydrolyzing phospholipase D—NAPE-PLD) and degradation (fatty acid amide hydrolase—FAAH) of PEA, and its receptor PPAR-α, is decreased in hippocampal CA1 (Blanco et al).…”

Partial Reversal of Striatal Damage by Palmitoylethanolamide Administration Following Perinatal Asphyxia

“…Notwithstanding that GFAP did not appear as an early marker of hippocampal damage after PA, we assessed the number of GFAP + astrocytes in the dorsal striatum based on our previously reported PA-induced changes in GFAP immunostaining in this region at P30 (Holubiec et al, 2017). Presently, PA induced a remarkable decrease in the number of astroglial cells.…”

“…Fifty-three male rat pups were subjected to PA using an experimental model (Bjelke et al, 1991), which produces moderate to severe PA (Van de Berg et al, 2003;Galeano et al, 2011) as we described previously (Capani et al, 2003(Capani et al, , 2009Saraceno et al, 2010Saraceno et al, , 2012aBlanco et al, 2015;Holubiec et al, 2017;Herrera et al, 2018). The murine model of PA, originally developed by Bjelke et al (1991), has been widely used (Barkhuizen et al, 2017;Herrera et al, 2017b) and accepted to mimic this condition (Capani et al, 1997(Capani et al, , 2003(Capani et al, , 2009Boksa and El-Khodor, 2003;Saraceno et al, 2010Saraceno et al, , 2012aStrackx et al, 2010;Muñiz et al, 2014;Romero et al, 2015;Wakuda et al, 2015;Herrera et al, 2018).…”

“…One hundred fifty by 150 µm was sampled in each photo to estimate the percentage of reactive area for pNF-H/M and MAP-2 using the Image J program (Image J 1.41o; NIH, United States). We analyzed the dorsal striatum because it is one of the most affected areas by PA insult (Holubiec et al, 2017). The number of GFAP immunoreactive astrocytes was manually estimated in the dorsal striatum.…”

“…Previous studies from our group using an animal model of PA (Bjelke et al, 1991) showed that PA-induced alterations are characterized by increased astrogliosis in the hippocampus and dorsal striatum (Cebral et al, 2006;Saraceno et al, 2010;Holubiec et al, 2017), reduced microtubule-associated protein 2 (MAP-2) level, and alterations in the phosphorylation of high-(200 kDa) and medium-(160 kDa) molecular-weight neurofilaments (pNF-H/M) in the hippocampus in 120-dayold rats (P120, postnatal day 120) (Saraceno et al, 2010) or 30-day-old rats (P30, postnatal day 30) (Herrera et al, 2018). Importantly, MAP-2 is predominantly localized in neuronal dendrites of the caudate, hippocampus, cerebral cortex, Abbreviations: ANOVA, analysis of variance; CNS, central nervous system; CO, carbon monoxide; GFAP, glial fibrillary acidic protein; HI, hypoxia-ischemia; HIE, hypoxia-ischemia encephalopathy; MAP-2, microtubule-associated protein-2; MPTP, 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine; PEA, palmitoylethanolamide; PA, perinatal asphyxia; PPARα, peroxisome proliferator-activated receptor alpha; pNF-H/M, phosphorylated high/medium-molecular-weight NF.…”