Canna~Fangled Abstracts

Impaired Neurogenesis by HIV-1-Gp120 is Rescued by genetic deletion of Fatty Acid Amide Hydrolase Enzyme.

By February 26, 2014 No Comments
2014 Feb 26. doi: 10.1111/bph.12657. [Epub ahead of print]

pm8Impaired Neurogenesis by HIV-1-Gp120 is Rescued by genetic deletion of Fatty Acid Amide Hydrolase Enzyme.

Abstract

BACKGROUND/PURPOSE:

The HIV-envelope glycoprotein Gp120 is involved in neuronal injury and is associated with neuro-AIDS pathogenesis in the brain. Endocannabinoids are important lipid ligands in the central nervous system (CNS) regulating neural functions, and their degeneration is controlled by hydrolyzing enzymes such as the fatty acid amide hydrolase (FAAH). Here, we examined whether in vivo genetic deletion of Faah gene prevents HIV-1 Gp120-mediated insults on neurogenesis.

EXPERIMENTAL APPROACH/KEY RESULTS:

We generated new GFAP/Gp120 transgenic (Tg) mice that have genetic deletion of Faah gene by mating GFAP/Gp120 Tg mice with Faah-/- mice. The endocannabinoid levels in the brain of these double GFAP/Gp120//Faah-/- mice were similar to those observed in Faah-/- mice. However, unlike the impaired neurogenesis observed in GFAP/Gp120 Tg mice and Faah-/- mice, these GFAP/Gp120//Faah-/ mice showed significantly improved neurogenesis in the hippocampus, indicated by a significant increase in neuroblasts and neuronal cells, an increase in BrdU+ cells and doublecortin positive cells (DCX+ ), as well as an increase in the number of proliferating cell nuclear antigen (PCNA). Further, a significant decrease in astrogliosis and gliogenesis was observed in GFAP/Gp120//Faah-/-mice and neurogenesis was stimulated by neural progenitor cells (NPCs) and/or the newly formed NPC niches characterized by induction of cyclooxygenase-2 (COX-2) expression and elevated levels of prostaglandin E2 (PGE-2).

CONCLUSION:

In vivo genetic ablation of Faah, resulted in enhanced neurogenesis through modulation of the newly generated NPC niches in GFAP/Gp120//Faah-/- mice. This suggests a novel approach of using FAAH inhibitors in enhancing neurogenesis in HIV-1 infected brain.
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KEYWORDS:

Endocannabinoids, Fatty acid amide hydrolase, Gp120 transgenic mice, HIV-1, Neural progenitor cells, Neurogenesis

PMID:

 

24571443

 

[PubMed – as supplied by publisher]
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