Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy

@article{Citraro2013AntiepilepticAO,
  title={Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-$\alpha$ receptor activation in a genetic model of absence epilepsy},
  author={Rita Citraro and Emilio Russo and Francesca Scicchitano and Clementina M. van Rijn and Donato Cosco and Carmen Avagliano and Roberto Russo and Giuseppe D'Agostino and Stefania Petrosino and Francesca Guida and Luisa Gatta and Gilles van Luijtelaar and Sabatino Maione and Vincenzo Di Marzo and Antonio Calignano and Giovambattista De Sarro},
  journal={Neuropharmacology},
  year={2013},
  volume={69},
  pages={115-126}
}
N-palmitoylethanolamine (PEA), an endogenous fatty acid ethanolamide, plays a key role in the regulation of the inflammatory response and pain through, among others, activation of nuclear peroxisome proliferator-activated receptors (PPAR-α). Endogenous cannabinoids play a protective role in several central nervous system (CNS) disorders, particularly those associated with neuronal hyperexcitability. We investigated the effects of PEA and the role of PPAR-α in absence epilepsy using the WAG/Rij… 
Pharmacokinetic-pharmacodynamic influence of N-palmitoylethanolamine, arachidonyl-2'-chloroethylamide and WIN 55,212-2 on the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.
TLDR
PEA, ACEA and WIN show anticonvulsant effects in DBA/2 mice and potentiate the effects several AEDs suggesting a possible therapeutic relevance of these drugs and their mechanisms of action.
Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy
TLDR
It is demonstrated that subchronic administration of PEA significantly alleviates seizure intensity, promotes neuroprotection and induces modulation of the plasma and hippocampal eCB and eiC levels in systemic KA-injected mice.
A role for peroxisome proliferator-activated receptor α in anticonvulsant activity of docosahexaenoic acid against seizures induced by pentylenetetrazole
TLDR
Peroxisome proliferator-activated receptors (PPARs) underlie some therapeutic effects of DHA such as anti-inflammation, anti-apoptosis and immune regulation and PPARα is involved in the anticonvulsant effect of D HA in PTZ model of clonic seizures in mice.
N-Palmitoylethanolamide Exerts Antidepressant-Like Effects in Rats: Involvement of PPARα Pathway in the Hippocampus
TLDR
The PPARα pathway in the hippocampus is a possible target of the antidepressant effects of PEA, and the maintenance of a stable hypothalamic-pituitary-adrenal axis, the antioxidant defenses, and normalization of neurotrophic factor levels inThe hippocampus are involved in this process.
Anti-kindling Effect of Bezafibrate, a Peroxisome Proliferator-activated Receptors Alpha Agonist, in Pentylenetetrazole Induced Kindling Seizure Model
TLDR
Bezafibrate significantly reduced the incidence of kindling in PTZ treated rats and exhibited a marked prolongation in the latencies to seizures, suggesting its potential for therapeutic applications in temporal lobe epilepsy.
Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma
TLDR
It is indicated that PPAR-δ and PPar-γ can also contribute to the anti-inflammatory activity of PEA in SCI, as evaluated by the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, proinflammmatory cytokine, inducible nitric oxide synthase expression and motor function.
Antiepileptogenic effects of the selective COX-2 inhibitor etoricoxib, on the development of spontaneous absence seizures in WAG/Rij rats
TLDR
The results confirm the antiepileptogenic effects of COX-2 inhibitors and suggest the possible role of COx-2, prostaglandin synthesis and consequent neuroinflammation in the epileptogenic process underlying the development of absence seizures in WAG/Rij rats.
Co-administration of cannabidiol and capsazepine reduces L-DOPA-induced dyskinesia in mice: Possible mechanism of action
TLDR
CBD, together with a TRPV-1 antagonist, reduces LID by acting on CB1 and PPARγ receptors and reducing the expression of the inflammatory markers cyclooxygenase-2 and nuclear factor-kappa B in the lesioned striatum.
Roles of N-Acylethanolamines in Brain Functions and Neuropsychiatric Diseases
TLDR
NAEs are bioactive lipids, structural analogues to the endocannabinoid arachidonoylethanolamide (anandamide), whose functions and properties are being elucidated in recent years and evidence suggests that they might be therapeutically exploited as neuroprotective agents, “anti-addictive” medications, anticonvulsant, and antidepressant.
Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures
TLDR
It seems extracellular accumulation of 2-AG or anandamide has anticonvulsive effect through the CB1 receptor, while intracellular anandamia accumulation is proconvulsive through TRPV1.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 64 REFERENCES
Central administration of palmitoylethanolamide reduces hyperalgesia in mice via inhibition of NF-kappaB nuclear signalling in dorsal root ganglia.
TLDR
It is reported that intracerebroventricular administration of PEA 30 min before carrageenan injection markedly reduced mechanical hyperalgesia up to 24 h following inflammatory insult, suggesting a centrally mediated component for these drugs in controlling inflammatory pain.
Acute Intracerebroventricular Administration of Palmitoylethanolamide, an Endogenous Peroxisome Proliferator-Activated Receptor-α Agonist, Modulates Carrageenan-Induced Paw Edema in Mice
TLDR
Central PEA administration significantly reduced the expression of the proinflammatory enzymes cyclooxygenase-2 and inducible nitric-oxide synthase, and it significantly restored carrageenan-induced PPAR-α reduction in the spinal cord, confirming the involvement of this transcriptional factor in the control of peripheral inflammation.
Palmitoylethanolamide, endocannabinoids and related cannabimimetic compounds in protection against tissue inflammation and pain: potential use in companion animals.
TLDR
Despite the multitude of therapies currently employed to control inflammation, pain, pruritus and tissue damage, the possibility of using a natural compound, such as PEA, to manipulate endogenous protective mechanisms may be considered a beneficial novel therapeutic strategy in veterinary medicine.
Involvement of the cannabimimetic compound, N-palmitoyl-ethanolamine, in inflammatory and neuropathic conditions: Review of the available pre-clinical data, and first human studies
TLDR
The hypothesis that PEA is an endogenous mediator whose levels are increased following neuroinflammatory or neuropathic conditions in both animals and humans, possibly to exert a local anti-inflammatory and analgesic action is substantiated.
The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-α Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide
TLDR
Findings indicate that PPAR-α mediates the anti-inflammatory effects of PEA and suggest that this fatty-acid ethanolamide may serve, like its analog OEA, as an endogenous ligand of PPar-α.
The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain
TLDR
The results confirm the analgesic potential of endogenous ligands at cannabinoid receptor sites and the anti‐nociceptive effect of the putative CB2 receptor agonist, palmitoylethanolamide, is particularly interesting since it is believed to be a peripherally mediated effect.
Attenuation of nerve growth factor-induced visceral hyperalgesia via cannabinoid CB1 and CB2-like receptors
TLDR
Investigation of the antihyperalgesic effects of two cannabinoids in NGF‐evoked visceral hyperalgesia supports the hypothesis that the endogenous cannabinoid system modulates the N GF‐mediated components of inflammatory processes.
The palmitoylethanolamide family: a new class of anti-inflammatory agents?
TLDR
In the present review, the biochemical and pharmacological properties of PEA are discussed, in particular with respect to its analgesic and anti-inflammatory properties.
Rapid Broad-Spectrum Analgesia through Activation of Peroxisome Proliferator-Activated Receptor-α
TLDR
It is reported that agonists of the nuclear receptor PPAR-α (peroxisome proliferator-activated receptor-α) suppress pain behaviors induced in mice by chemical tissue injury, nerve damage, or inflammation and may represent a novel class of analgesics.
Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-α
TLDR
The results, which show that OEA induces satiety by activating PPAR-α, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders, are identified.
...
1
2
3
4
5
...