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

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 CB...

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Published in:	Psychopharmacology Vol. 235; no. 10; pp. 2929 - 2945
Main Authors:	Holubiec, Mariana I., Romero, Juan I., Suárez, Juan, Portavella, Manuel, Fernández-Espejo, Emilio, Blanco, Eduardo, Galeano, Pablo, de Fonseca, Fernando Rodríguez
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 01-10-2018 Springer Springer Nature B.V
Subjects:	Amides Animals Anoxia Astrocytes Biomedical and Life Sciences Biomedicine Cannabinoid CB2 receptors Central nervous system Cognitive ability Disease Models, Animal Endocannabinoids - pharmacology Ethanolamines - pharmacology Fatty acids Female Gliosis Glucose - pharmacology Glucose metabolism Health aspects Hippocampus - drug effects Hypoxia-Ischemia, Brain - drug therapy Hypoxia-Ischemia, Brain - metabolism Hypoxia-Ischemia, Brain - physiopathology Inflammation Ischemia Lipid Metabolism Locomotion Locomotion - drug effects Neonatal diseases Neonates Nervous system diseases Neurosciences Newborn babies Oleic acid Oleic Acids - pharmacology Original Investigation Palmitic Acids - pharmacology Palmitoylethanolamide Pharmacology/Toxicology Physiological aspects PPAR alpha - metabolism Prevention Psychiatry Psychological aspects Rats Rats, Sprague-Dawley Recognition (Memory) Recognition (Psychology) - drug effects Spatial memory Spatial Memory - drug effects Astrogliosis Memory impairment Neuroinflammation Neonatal anoxia-ischemia Oleoylethanolamide Palmitoylethanolamide
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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.
AbstractList	RationalNeonatal 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.ObjectiveIn 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.MethodsTo 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.ResultsResults 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.ConclusionsThese 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. Rational 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. 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. 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. 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. 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. 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 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. 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. 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. RATIONALNeonatal 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.OBJECTIVEIn 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.METHODSTo 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.RESULTSResults 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.CONCLUSIONSThese 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. 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 (PPAR[alpha]), 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 PPAR[alpha] 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.
Audience	Academic
Author	Blanco, Eduardo Galeano, Pablo de Fonseca, Fernando Rodríguez Holubiec, Mariana I. Suárez, Juan Portavella, Manuel Fernández-Espejo, Emilio Romero, Juan I.
Author_xml	– sequence: 1 givenname: Mariana I. surname: Holubiec fullname: Holubiec, Mariana I. organization: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) – sequence: 2 givenname: Juan I. surname: Romero fullname: Romero, Juan I. organization: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) – sequence: 3 givenname: Juan surname: Suárez fullname: Suárez, Juan organization: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga – sequence: 4 givenname: Manuel surname: Portavella fullname: Portavella, Manuel organization: Laboratorio de Conducta Animal y Neurociencia, Departamento de Psicología Experimental, Facultad de Psicología, Universidad de Sevilla – sequence: 5 givenname: Emilio surname: Fernández-Espejo fullname: Fernández-Espejo, Emilio organization: Laboratorio de Neurofisiología y Neurología Molecular, Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla – sequence: 6 givenname: Eduardo surname: Blanco fullname: Blanco, Eduardo organization: Lleida Institute for Biomedical Research, Dr. Pifarré Foundation (IRBLleida), University of Lleida – sequence: 7 givenname: Pablo orcidid: 0000-0003-4491-2039 surname: Galeano fullname: Galeano, Pablo email: pgaleano@leloir.org.ar organization: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) – sequence: 8 givenname: Fernando Rodríguez surname: de Fonseca fullname: de Fonseca, Fernando Rodríguez email: fernando.rodriguez@ibima.eu organization: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga
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PublicationDate	2018-10-01
PublicationDateYYYYMMDD	2018-10-01
PublicationDate_xml	– month: 10 year: 2018 text: 2018-10-01 day: 01
PublicationDecade	2010
PublicationPlace	Berlin/Heidelberg
PublicationPlace_xml	– name: Berlin/Heidelberg – name: Germany – name: Heidelberg
PublicationTitle	Psychopharmacology
PublicationTitleAbbrev	Psychopharmacology
PublicationTitleAlternate	Psychopharmacology (Berl)
PublicationYear	2018
Publisher	Springer Berlin Heidelberg Springer Springer Nature B.V
Publisher_xml	– name: Springer Berlin Heidelberg – name: Springer – name: Springer Nature B.V
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Snippet	Rational Neonatal anoxia-ischemia (AI) particularly affects the central nervous system. Despite the many treatments that have been tested, none of them has... 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... Rational Neonatal anoxia-ischemia (AI) particularly affects the central nervous system. Despite the many treatments that have been tested, none of them has... Rational 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... RationalNeonatal anoxia-ischemia (AI) particularly affects the central nervous system. Despite the many treatments that have been tested, none of them has... RATIONALNeonatal anoxia-ischemia (AI) particularly affects the central nervous system. Despite the many treatments that have been tested, none of them has...
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SubjectTerms	Amides Animals Anoxia Astrocytes Biomedical and Life Sciences Biomedicine Cannabinoid CB2 receptors Central nervous system Cognitive ability Disease Models, Animal Endocannabinoids - pharmacology Ethanolamines - pharmacology Fatty acids Female Gliosis Glucose - pharmacology Glucose metabolism Health aspects Hippocampus - drug effects Hypoxia-Ischemia, Brain - drug therapy Hypoxia-Ischemia, Brain - metabolism Hypoxia-Ischemia, Brain - physiopathology Inflammation Ischemia Lipid Metabolism Locomotion Locomotion - drug effects Neonatal diseases Neonates Nervous system diseases Neurosciences Newborn babies Oleic acid Oleic Acids - pharmacology Original Investigation Palmitic Acids - pharmacology Palmitoylethanolamide Pharmacology/Toxicology Physiological aspects PPAR alpha - metabolism Prevention Psychiatry Psychological aspects Rats Rats, Sprague-Dawley Recognition (Memory) Recognition (Psychology) - drug effects Spatial memory Spatial Memory - drug effects
Title	Palmitoylethanolamide prevents neuroinflammation, reduces astrogliosis and preserves recognition and spatial memory following induction of neonatal anoxia-ischemia
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