Glial Modulation by N-acylethanolamides in Brain Injury and Neurodegeneration

Herrera, María Inés; Kölliker-Frers, Rodolfo; Barreto, George E.; Blanco, Eduardo; Capani, Francisco

doi:10.3389/fnagi.2016.00081

Cited by 21 publications

(17 citation statements)

References 102 publications

(215 reference statements)

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“…Furthermore, our findings agree with previous reports on the protective effects of PEA in experimental neurodegeneration (Skaper et al, 1996;Esposito et al, 2012;Scuderi et al, 2014;Herrera et al, 2016). PEA protected from the decrease in MAP-2 expression induced by amyloid peptides (Scuderi et al, 2014;Tomasini et al, 2015) and by MPTP in an animal model of Parkinson's disease (Esposito et al, 2012).…”

Section: Discussionsupporting

confidence: 92%

“…One month after a severe, 20-min PA, the rats developed an alteration in the endocannabinoid system expression and related acylethanolamide pathways (Blanco et al, 2015). Palmitoylethanolamide (PEA) is an endogenous lipidic neuromodulator related to endocannabinoids, acting as a peroxisome proliferator-activated receptor alpha (PPARα) or G protein-coupled receptor 55 (GPR55) agonist that elicits anti-inflammatory, neuroprotective, and restorative properties (Mattace Raso et al, 2014;Petrosino and Di Marzo, 2017) in vitro (Avagliano et al, 2016), in animal models of both neurodegeneration (Esposito et al, 2011(Esposito et al, , 2012(Esposito et al, , 2014Herrera et al, 2016) and hypoxia-ischemia (HI) (Fernandez-Lopez et al, 2013;England et al, 2015), and in human patients as well (Orefice et al, 2016). Interestingly, one study reported that natives from Puno at about 3,830 m above sea level in Peru, having high hemoglobinemia and low oxygen saturation, also exhibited a high plasma concentration of PEA (Alarcon-Yaquetto et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Partial Reversal of Striatal Damage by Palmitoylethanolamide Administration Following Perinatal Asphyxia

et al. 2020

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Perinatal asphyxia (PA) is a clinical condition brought by a birth temporary oxygen deprivation associated with long-term damage in the corpus striatum, one of the most compromised brain areas. Palmitoylethanolamide (PEA) is a neuromodulator well known for its protective effects in brain injury models, including PA, albeit not deeply studied regarding its particular effects in the corpus striatum following PA. Using Bjelke et al. (1991) PA model, full-term pregnant rats were decapitated, and uterus horns were placed in a water bath at 37 • C for 19 min. One hour later, the pups were injected with PEA 10 mg/kg s.c., and placed with surrogate mothers. After 30 days, the animals were perfused, and coronal striatal sections were collected to analyze protein-level expression by Western blot and the reactive area by immunohistochemistry for neuron markers: phosphorylated neurofilament-heavy/medium-chain (pNF-H/M) and microtubule-associated protein-2 (MAP-2), and the astrocyte marker, glial fibrillary acidic protein (GFAP). Results indicated that PA produced neuronal damage and morphological changes. Asphyctic rats showed a decrease in pNF-H/M and MAP-2 reactive areas, GFAP + cells number, and MAP-2 as well as pNF-H/M protein expression in the striatum. Treatment with PEA largely restored the number of GFAP + cells. Most important, it ameliorated the decrease in pNF-H/M and MAP-2 reactive areas in asphyctic rats. Noticeably, PEA treatment reversed the decrease in MAP-2 protein expression and largely prevented PA-induced decrease in pNF-H/M protein expression. PA did not affect the GFAP protein level. Treatment with PEA attenuated striatal damage induced by PA, suggesting its therapeutic potential for the prevention of neurodevelopmental disorders.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Partial Reversal of Striatal Damage by Palmitoylethanolamide Administration Following Perinatal Asphyxia

et al. 2020

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“…The exact mechanism of PEA action remains to be elucidated in further studies. Nevertheless, emerging evidence supports the notion that the neuroprotective and anti-inflammatory effect of PEA occurs through complex mechanisms involving interactions between microglial and non-neuronal cells of immune origin such as mast cells in the CNS, and with mast cells and macrophages in the periphery (Skaper et al, 2013 ; Herrera et al, 2016 ; Guida et al, 2017 ). In periphery, PEA completely reverses the upregulation of eCBs and eiCs, e.g., 2-AG and PGE 2 in acute phase and maintains low the level of AEA-AA till acute phase, likely in order to tune down the rise of KA-derived peripheral inflammation by restricting the AA pool for PGs synthesis.…”

Section: Discussionmentioning

confidence: 99%

Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy

Post

Loch

Lerner

et al. 2018

Front. Mol. Neurosci.

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Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]). Concomitant research has uncovered the contribution of neuroinflammatory processes and peripheral immunity to the onset and progression of epilepsy. Accordingly, modulation of inflammatory pathways such as cyclooxygenase-2 (COX-2) was pursued as alternative therapeutic strategy for epilepsy. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide related to the centrally and peripherally present eCB AEA, and is a naturally occurring nutrient that has long been recognized for its analgesic and anti-inflammatory properties. Neuroprotective and anti-hyperalgesic properties of PEA were evidenced in neurodegenerative diseases, and antiepileptic effects in pentylenetetrazol (PTZ), maximal electroshock (MES) and amygdaloid kindling models of epileptic seizures. Moreover, numerous clinical trials in chronic pain revealed that PEA treatment is devoid of addiction potential, dose limiting side effects and psychoactive effects, rendering PEA an appealing candidate as antiepileptic compound or adjuvant. In the present study, we aimed at assessing antiepileptic properties of PEA in a mouse model of acute epileptic seizures induced by systemic administration of kainic acid (KA). KA-induced epilepsy in rodents is assumed to resemble to different extents human temporal lobe epilepsy (TLE) depending on the route of KA administration; intracerebral (i.c.) injection was recently shown to most closely mimic human TLE, while systemic KA administration causes more widespread pathological damage, both in brain and periphery. To explore the potential of PEA to exert therapeutic effects both in brain and periphery, acute and subchronic administration of PEA by intraperitoneal (i.p.) injection was assessed on mice with systemically administered KA. Specifically, we investigated: (i) neuroprotective and anticonvulsant properties of acute and subchronic PEA treatment in KA-induced seizure models, and (ii) temporal dynamics of eCB and eicosanoid (eiC) levels in hippocampus and plasma over 180 min post seizure induction in PEA-treated and non-treated KA-injected mice vs. vehicle injected mice. Finally, we compared the systemic PEA treatment with, and in combination with, pharmacological blockade of fatty acid amide hydrolase (FAAH) in brain and periphery, in terms of anticonvulsant properties and modulation of eCBs and eiCs. Here, we demonstrate that subchronic administration of PEA significantly alleviates seizure intensit...

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“…OEA, a monounsaturated lipid mediator and a bioactive molecule, belongs to the acyethanolamides family ( Figure 2) is synthesized in the proximal small intestine from oleic acid and phosphatidylethanolamine by N-acyltransferase (NAT) enzyme in the cellular membrane (Brown, Karimian Azari, & Ayala, 2017). OEA also is expressed in other tissues such as adipose tissues (Schmid, Wold, Krebsbach, Berdyshev, & Schmid, 2002), neurons (Hu & Mackie, 2015), and astrocytes (Herrera, Kölliker-Frers, Barreto, Blanco, & Capani, 2016).…”

Section: Various Nutraceutical and Pharmaceutical Compounds Have Beenmentioning

confidence: 99%

Oleoylethanolamide: A novel pharmaceutical agent in the management of obesity‐an updated review

Payahoo

Khajebishak

Ostadrahimi

2018

Journal Cellular Physiology

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Obesity as a multifactorial disorder has been shown a dramatically growing trend recently. Besides genetic and environmental factors, dysregulation of the endocannabinoid system tone is involved in the pathogenesis of obesity. This study reviewed the potential efficacy of Oleoylethanolamide (OEA) as an endocannabinoid‐like compound in the energy homeostasis and appetite control in people with obesity. OEA as a lipid mediator and bioactive endogenous ethanolamide fatty acid is structurally similar to the endocannabinoid system compounds; nevertheless, it is unable to induce to the cannabinoid receptors. Unlike endocannabinoids, OEA negatively acts on the food intake and suppress appetite via various mechanisms. Indeed, OEA as a ligand of PPAR‐α, GPR‐119, and TRPV1 receptors participates in the regulation of energy intake and energy expenditure, feeding behavior, and weight gain control. OEA delays meal initiation, reduces meal size, and increases intervals between meals. Considering side effects of some approaches used for the management of obesity such as antiobesity drugs and surgery as well as based on sufficient evidence about the protective effects of OEA in the improvement of common abnormalities in people with obese, its supplementation as a novel efficient and FDA approved pharmaceutical agent can be recommended.

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Glial Modulation by N-acylethanolamides in Brain Injury and Neurodegeneration

Cited by 21 publications

References 102 publications

Partial Reversal of Striatal Damage by Palmitoylethanolamide Administration Following Perinatal Asphyxia

Partial Reversal of Striatal Damage by Palmitoylethanolamide Administration Following Perinatal Asphyxia

Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy

Oleoylethanolamide: A novel pharmaceutical agent in the management of obesity‐an updated review

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