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Immunohistochemical localization of anabolic and catabolic enzymes for anandamide and other putative endovanilloids in the hippocampus and cerebellar cortex of the mouse brain

Cristino, L., Starowicz, K., De Petrocellis, L., Morishita, J., Ueda, N., Guglielmotti, V., Di Marzo, V.·2008·Neuroscience
DOI 10.1016/j.neuroscience.2007.11.047
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Abstract

An increasing body of evidence indicates that: 1) the endocannabinoid anandamide (AEA) and other unsaturated N-acylethanolamines (NAEs), 2) 12-(S)-lipoxygenase (12-LOX) products of arachidonic acid, and 3) unsaturated N-acyldopamines (NADAs), act as endogenous ligands of transient receptor potential vanilloid type 1 (TRPV1) channels at intracellular binding sites. AEA is synthesized and released "on demand" in neurons from its membrane precursor, N-arachidonoyl-phosphatidylethanolamine, by an N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), and is inactivated by intracellular hydrolysis by fatty acid amide hydrolase (FAAH), whereas catechol-O-methyl-transferase (COMT) was suggested to inactivate NADAs. However, it is not known whether these enzymes or 12-LOX co-localize to any extent with TRPV1 receptors in the brain. In this study we used immunohistochemical techniques (single peroxidase and double immunofluorescence staining), and analyzed the localization of the TRPV1 channel in mouse hippocampal and cerebellar neurons with respect to NAPE-PLD, FAAH, 12-LOX and COMT. Cycloxygenase-2 (COX-2), another putative AEA-degrading enzyme, was also studied. Co-localization between TRPV1 and either NAPE-PLD or FAAH, COX-2, 12-LOX and COMT was found in Ammon's horn (CA3) hippocampal pyramidal neurons and (with the exception of 12-LOX) in some Purkinje cells. At the cellular level, both anabolic and catabolic enzymes appeared as fine grains with immunoperoxidase labeling and were observed in the somatodendritic compartment of CA3 pyramidal cells as well as (with the exception of 12-LOX) in the cytoplasm of Purkinje neurons, in which FAAH and COX-2 immunoreactivities were, however, preferentially localized in the large extension of the dendritic arbor. Our data agree with the hypothesis that, in potential "endovanillergic" neurons, endogenous TRPV1 agonists, and AEA in particular, act as intracellular mediators by being produced from and/or degraded by the same mouse brain cells that express TRPV1 receptors.

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Crossref · 10.1016/j.neuroscience.2007.11.047

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  • COX-2 is primarily expressed postsynaptically and localizes to dendritic spines and dendrites in an expression pattern strikingly similar to that of FAAH.

    “COX-2 is primarily expressed postsynaptically and localizes to dendritic spines and dendrites in an expression pattern strikingly similar to that of FAAH (Cristino et al., 2008).”

    From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Cristino et al., 2008

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Authors
Cristino, L., Starowicz, K., De Petrocellis, L., Morishita, J., Ueda, N., Guglielmotti, V., & Di Marzo, V.
Affiliations
  • Institute of Applied Science and Intelligent Systems (IT)
  • Istituto di Chimica Biomolecolare (IT)
  • Kagawa University (JP)
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2008-02
Volume
151
Issue
4
Pages
955-968
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2007.11.047
OpenAlex
W2024356032
Cited by
115
References
70
Citations by year
2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 11 · 2016: 3 · 2015: 5 · 2014: 8 · 2013: 8 · 2012: 11
FWCI
7.53
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
anandamide, endocannabinoids, endovanilloids, TRPV1, fatty acid amide hydrolase, 12-lipoxygenase, catechol-O-methyltransferase, cyclooxygenase-2, N-acylethanolamines, hippocampus, cerebellar cortex, Purkinje cells, CA3 pyramidal cells, enzyme colocalization
MeSH terms
Fatty Acid Amide Hydrolases, Amidohydrolases, Animals, Arachidonate 12-Lipoxygenase, Catechol O-Methyltransferase, Cerebellar Cortex, Glutamate Decarboxylase, Hippocampus, Male, Neurons, Phospholipase D, TRPV Cation Channels, Mice, Cyclooxygenase 2

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