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Palmitoylethanolamide prevents neuroinflammation, reduces astrogliosis and preserves recognition and spatial memory following induction of neonatal anoxia-ischemia

Abstract

Rational

Neonatal anoxia-ischemia (AI) particularly affects the central nervous system. Despite the many treatments that have been tested, none of them has proven to be completely successful. Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are acylethanolamides that do not bind to CB1 or CB2 receptors and thus they do not present cannabinoid activity. These molecules are agonist compounds of peroxisome proliferator-activator receptor alpha (PPARα), which modulates the expression of different genes that are related to glucose and lipid metabolism, inflammation, differentiation and proliferation.

Objective

In the present study, we analyzed the effects that the administration of PEA or OEA, after a neonatal AI event, has over different areas of the hippocampus.

Methods

To this end, 7-day-old rats were subjected to AI and then treated with vehicle, OEA (2 or 10 mg/kg) or PEA (2 or 10 mg/kg). At 30 days of age, animals were subjected to behavioral tests followed by immunohistochemical studies.

Results

Results showed that neonatal AI was associated with decreased locomotion, as well as recognition and spatial memory impairments. Furthermore, these deficits were accompanied with enhanced neuroinflammation and astrogliosis, as well as a decreased PPARα expression. PEA treatment was able to prevent neuroinflammation, reduce astrogliosis and preserve cognitive functions.

Conclusions

These results indicate that the acylethanolamide PEA may play an important role in the mechanisms underlying neonatal AI, and it could be a good candidate for further studies regarding neonatal AI treatments.

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Acknowledgments

This work was supported by grants from Fundació “La Marató de TV3” (386/C/2011), European Regional Development Funds-European Union (ERDF-EU; Subprograma RETICS Red de Trastornos Adictivos RD16/0017/0001), Ministerio de Economía y Competitividad and ISCIII (PI16/01689) to FRF; Own Plan of the Andalucía TECH, International Campus of Excellence (ICE) to PG, and grants to EFE and FRF from Junta de Andalucía, Spain (EFE, group BIO-127; FRF, group BIO-339). JS holds a “Miguel Servet II” research contract from the National System of Health, ISCIII, EU-ERDF (CPII17/00024). Mariana I. Holubiec is a fellowship holder from Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT, Argentina). Eduardo Blanco is an associate professor of the Serra-Hunter Programme from the Catalan Government. Juan I. Romero and Pablo Galeano are research members from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Argentina).

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Correspondence to Pablo Galeano or Fernando Rodríguez de Fonseca.

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On behalf of all authors, corresponding authors state that there is no conflict of interest.

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Holubiec, M.I., Romero, J.I., Suárez, J. et al. Palmitoylethanolamide prevents neuroinflammation, reduces astrogliosis and preserves recognition and spatial memory following induction of neonatal anoxia-ischemia. Psychopharmacology 235, 2929–2945 (2018). https://doi.org/10.1007/s00213-018-4982-9

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  • DOI: https://doi.org/10.1007/s00213-018-4982-9

Keywords

  • Neonatal anoxia-ischemia
  • Palmitoylethanolamide
  • Oleoylethanolamide
  • Neuroinflammation
  • Astrogliosis
  • Memory impairment