A Personal Retrospective: Elevating Anandamide (AEA) by Targeting Fatty Acid Amide Hydrolase (FAAH) and the Fatty Acid Binding Proteins (FABPs)

Fetal examinations in embryo-fetal developmental (EFD) studies are based on macroscopic and dissecting microscopic evaluations, and histopathology is rarely performed other than to confirm macroscopic findings. Fetal lens examination is therefore generally limited to the presence, size, shape, and color of any abnormality. In a Sprague-Dawley rat EFD study with the fatty acid amide hydrolase (FAAH) inhibitor JNJ-42165279, an unusually high incidence of macroscopic granular foci was noted within the lens of gestation day 21 fetuses across all groups including controls, with higher incidence in the high-dose group. On histological evaluation of the lenses from fetuses with/without gross findings, primary lens fiber hypertrophy (swelling) and degeneration were observed across vehicle- and JNJ-42165279-exposed fetuses. In a follow-up study to investigate the progression or resolution of the fetal lens changes, animals exposed to suprapharmacological doses of JNJ-42165279 in utero had higher incidence of nuclear cataracts as detected via slit-lamp ophthalmic examinations on postnatal days 18 to 21 and 35 to 41. No histologic correlates for these cataracts were identified. We conclude that fetal primary lens fiber hypertrophy and nuclear cataracts at ophthalmology, are common background changes in this rat strain that are exacerbated by in utero exposure to the FAAH inhibitor JNJ-42165279.

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S203. Fatty Acid Amide Hydrolase Polymorphism C385A Associated With Dopamine D2/3 Receptor Levels: A PET Study With [11C]-(+)-PHNO

Biological Psychiatry ◽

10.1016/j.biopsych.2019.03.954 ◽

2019 ◽

Vol 85 (10) ◽

pp. S376

Author(s):

Esmaeil Mansouri ◽

Rachel F. Tyndale ◽

Christian S. Hendershot ◽

Laura M. Best ◽

Patricia Di Ciano ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Amide Hydrolase ◽

Acid Amide ◽

Dopamine D2 ◽

Amide Hydrolase ◽

Fatty Acid Amide

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Fatty Acid Amide Hydrolase Deficiency Enhances Intraplaque Neutrophil Recruitment in Atherosclerotic Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.112.300275 ◽

2013 ◽

Vol 33 (2) ◽

pp. 215-223 ◽

Cited By ~ 36

Author(s):

Sébastien Lenglet ◽

Aurélien Thomas ◽

Oliver Soehnlein ◽

Fabrizio Montecucco ◽

Fabienne Burger ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Amide Hydrolase ◽

Acid Amide ◽

Neutrophil Recruitment ◽

Amide Hydrolase ◽

Fatty Acid Amide

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Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review

International Journal of Molecular Sciences ◽

10.3390/ijms22031047 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1047

Author(s):

Dorsa Rafiei ◽

Nathan J. Kolla

Keyword(s):

Depressive Symptoms ◽

Fatty Acid ◽

Animal Models ◽

Fatty Acid Amide Hydrolase ◽

Acid Amide ◽

Endocannabinoid System ◽

Animal Models Of Depression ◽

Amide Hydrolase ◽

Fatty Acid Amide

Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

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