Endocannabinoid-Making Enzymes and CB1 Receptors Are Expressed Together in Mouse Brains | Research

The takeaway

CB1 receptor expression in mouse brains correlated with the expression of enzymes that make and break down endocannabinoids, but dietary arachidonic acid didn't change any of them.

Read this if you're interested in how the brain's endocannabinoid system is internally regulated.

CB1 receptor expression correlated with enzymes that make its ligands

What the researchers found

Researchers investigated whether feeding mice arachidonic acid (AA), the fatty acid building block of endocannabinoids, would change the expression of endocannabinoid-related genes in the brain.

Mice received varying amounts of AA-rich oil (0, 100, 200, or 300 microliters) orally for 7 days. Despite this dietary manipulation, no changes in brain gene expression were detected for any endocannabinoid-related enzyme or the CB1 receptor.

However, the study revealed a significant correlation: CB1 receptor expression was positively correlated with the expression of PLD (which makes anandamide), FAAH (which breaks down anandamide), and DAGL (which makes 2-AG). This coordinated expression suggests the endocannabinoid system is tightly regulated as a unit rather than having independently controlled components.

Why it matters

The finding that endocannabinoid enzymes and their receptor are co-regulated suggests the system maintains internal balance. The lack of dietary influence on gene expression indicates the brain's endocannabinoid system is robust against short-term nutritional changes.

The numbers in context

Four AA dose groups (0, 100, 200, 300 microliters). 7 days of treatment. CB1 receptor mRNA positively correlated with PLD, FAAH, and DAGL expression. No dose-dependent changes in any measured gene.

How the study worked

Male mice received oral AA-rich oil at four dose levels for 7 days. Whole brain mRNA expression of PLD, FAAH, DAGL, MAGL, and CB1 receptor was measured and analyzed for dose-response effects and inter-gene correlations.

What this study cannot tell us

Whole brain homogenates were used, which could mask region-specific changes. The 7-day treatment period may be too short to observe dietary effects. Only mRNA was measured, not protein levels or enzyme activity. Small sample typical of mouse studies.

How to read the evidence

This is a small animal study examining gene expression correlations. While the finding is interesting, it is preliminary and the functional significance requires further investigation.

When this study was published

Published in 2007. Understanding of endocannabinoid system regulation has advanced significantly since then.

The bigger picture

The coordinated expression of endocannabinoid system components suggests a tightly regulated system. This has implications for drug development: targeting one component may trigger compensatory changes in others, potentially limiting therapeutic effects.

Questions still open

Would longer-term dietary changes affect endocannabinoid gene expression? Do regional differences in this coordinated expression exist? Does the co-regulation change in disease states?

Common questions

Can diet change your endocannabinoid system?

This short-term study found that dietary arachidonic acid did not change brain endocannabinoid gene expression in mice. However, other research has found that long-term dietary patterns (particularly omega-3 to omega-6 fatty acid ratios) may influence endocannabinoid levels.

What does coordinated expression mean?

It means that when CB1 receptor levels are higher, the enzymes that make and break down endocannabinoids are also higher. The system appears to scale up or down as a unit rather than having independently regulated parts.

Read the original research

Expression of endocannabinoid synthetic enzyme mRnas is correlated with cannabinoid 1 receptor mRNA in the mouse brain.

Nutritional neuroscience, 10(1-2), 45-50

View on PubMed ↗

Citation

Tsuyama, Shoichiro; Oikawa, Daichi; Yamasaki, Yasuko; Takagi, Sayuri; Ando, Hironori; Furuse, Mitsuhiro. (2007). Expression of endocannabinoid synthetic enzyme mRnas is correlated with cannabinoid 1 receptor mRNA in the mouse brain.. Nutritional neuroscience, 10(1-2), 45-50.