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Metabotropic Glutamate Receptor 5 and 8 Modulate the Ameliorative Effect of Ultramicronized Palmitoylethanolamide on Cognitive Decline Associated with Neuropathic Pain
- Source :
- International Journal of Molecular Sciences, Volume 20, Issue 7, International Journal of Molecular Sciences, Vol 20, Iss 7, p 1757 (2019)
- Publication Year :
- 2019
-
Abstract
- This study investigated whether metabotropic glutamate receptor (mGluR) 5 and 8 are involved in the effect of ultramicronizedpalmitoylethanolamide (um-PEA) on the cognitive behavior and long term potentiation (LTP) at entorhinal cortex (LEC)-dentate gyrus (DG) pathway in mice rendered neuropathic by the spare nerve injury (SNI). SNI reduced discriminative memory and LTP. Um-PEA treatment started after the development of neuropathic pain had no effects in sham mice, whereas it restored cognitive behavior and LTP in SNI mice. 2-Methyl-6-(phenylethynyl) pyridine (MPEP), a selective mGluR5 antagonist, improved cognition in SNI mice and produced a chemical long term depression of the field excitatory postsynaptic potentials (fEPSPs) in sham and SNI mice. After theta burst stimulation (TBS) MPEP restored LTP in SNI mice. In combination with PEA, MPEP antagonized the PEA effect on discriminative memory and decreased LTP in SNI mice. The (RS)-4-(1-amino-1-carboxyethyl)phthalic acid (MDCPG), a selective mGluR8 antagonist, did not affect discriminative memory, but it induced a chemical LTP and prevented the enhancement of fEPSPs after TBS in SNI mice which were treated or not treated with PEA. The effect of PEA on LTP and cognitive behavior was modulated by mGluR5 and mGluR8. In particular in the SNI conditions, the mGluR5 blockade facilitated memory and LTP, but prevented the beneficial effects of PEA on discriminative memory while the mGluR8 blockade, which was ineffective in itself, prevented the favorable action of the PEA on LTP. Thus, although their opposite roles (excitatory/inhibitory of the two receptor subtypes on the glutamatergic system), they appeared to be required for the neuroprotective effect of PEA in conditions of neuropathic pain.
- Subjects :
- Male
0301 basic medicine
Pyridines
Long-Term Potentiation
spared nerve injury
Pharmacology
Receptors, Metabotropic Glutamate
lcsh:Chemistry
Mice
chemistry.chemical_compound
0302 clinical medicine
Peripheral Nerve Injuries
Cognitive decline
long term potentiation
Long-term depression
lcsh:QH301-705.5
Spectroscopy
Metabotropic glutamate receptor 5
musculoskeletal, neural, and ocular physiology
food and beverages
metabotropic glutamate receptor 5 and 8
Long-term potentiation
General Medicine
Computer Science Applications
Olfactory Cortex
Ethanolamines
lateral entorhinal cortex-dentate gyrus
Excitatory postsynaptic potential
SNi
Receptor, Metabotropic Glutamate 5
Palmitic Acids
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
ultramicronizedpamitoylethanolamide
Memory
Animals
Humans
Physical and Theoretical Chemistry
Molecular Biology
Palmitoylethanolamide
Organic Chemistry
Excitatory Postsynaptic Potentials
Amides
Disease Models, Animal
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
nervous system
chemistry
Metabotropic glutamate receptor
Dentate Gyrus
Neuralgia
discriminative memory
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences, Volume 20, Issue 7, International Journal of Molecular Sciences, Vol 20, Iss 7, p 1757 (2019)
- Accession number :
- edsair.doi.dedup.....95e2dd999bd413506f3b1845fe7d172f