Dual mechanism of TRKB activation by anandamide through CB1 and TRPV1 receptors

Show full item record



Permalink

http://hdl.handle.net/10138/299992

Citation

Diniz , C R A F , Biojone , C , Joca , S R L , Rantamäki , T , Castren , E , Guimaraes , F S & Casarotto , P C 2019 , ' Dual mechanism of TRKB activation by anandamide through CB1 and TRPV1 receptors ' , PeerJ , vol. 7 , 6493 . https://doi.org/10.7717/peerj.6493

Title: Dual mechanism of TRKB activation by anandamide through CB1 and TRPV1 receptors
Author: Diniz, Cassiano R. A. F.; Biojone, Caroline; Joca, Samia R. L.; Rantamäki, Tomi; Castren, Eero; Guimaraes, Francisco S.; Casarotto, Plinio C.
Contributor: University of Helsinki, Neuroscience Center
University of Helsinki, Drug Research Program
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
Date: 2019-02-21
Language: eng
Number of pages: 21
Belongs to series: PeerJ
ISSN: 2167-8359
URI: http://hdl.handle.net/10138/299992
Abstract: Background. Administration of anandamide (AEA) or 2-arachidonoylglycerol (2AG) induces CB1 coupling and activation of TRKB receptors, regulating the neuronal migration and maturation in the developing cortex. However, at higher concentrations AEA also engages vanilloid receptor TRPV1, usually with opposed consequences on behavior. Methods and Results. Using primary cell cultures from the cortex of rat embryos (E18) we determined the effects of AEA on phosphorylated TRKB (pTRK). We observed that AEA (at 100 and 200 nM) induced a significant increase in pTRK levels. Such effect of AEA at 100 nM was blocked by pretreatment with the CBI antagonist AM251 (200 nM) and, at the higher concentration of 200 nM by the TRPV1 antagonist capsazepine (200 nM), but mildly attenuated by AM251. Interestingly, the effect of AEA or capsaicin (a TRPV1 agonist, also at 200 nM) on pTRK was blocked by TRKB.Fc (a soluble form of TRKB able to bind BDNF) or capsazepine, suggesting a mechanism dependent on BDNF release. Using the marble-burying test (MBT) in mice, we observed that the local administration of ACEA (a CBI agonist) into the prelimbic region of prefrontal cortex (PL-PFC) was sufficient to reduce the burying behavior, while capsaicin or BDNF exerted the opposite effect, increasing the number of buried marbles. In addition, both ACEA and capsaicin effects were blocked by previous administration of k252a (an antagonist of TRK receptors) into PL-PFC. The effect of systemically injected CB1 agonist WIN55,212-2 was blocked by previous administration of k252a. We also observed a partial colocalization of CBI /TRPV1 /TRKB in the PL-PFC, and the localization of TRPV1 in CaMK2+ cells. Conclusion. Taken together, our data indicate that anandamide engages a coordinated activation of TRKB, via CB1 and TRPV1. Thus, acting upon CBI. and TRPV1, AEA could regulate the TRKB-dependent plasticity in both pre- and postsynaptic compartments.
Subject: TRPV1
CB1
BDNF
Marble-burying
MARBLE-BURYING BEHAVIOR
VANILLOID TYPE-1 TRPV1
MEDIAL PREFRONTAL CORTEX
REPETITIVE BEHAVIOR
INHIBITORY SYNAPSES
SYNAPTIC PLASTICITY
NEUROTROPHIC FACTOR
CANNABINOID TYPE-1
ENDOCANNABINOIDS
3112 Neurosciences
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
peerj_art6493.pdf 3.331Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record