Epigenetics of the Cannabinoid System (Onder Albayram)

In this episode of the Epigenetics Podcast, we talked with Onder Albayram from the Medical University of South Carolina about the role of the endocannabinoid system in brain aging and neuroprotection.

A major part of the conversation focuses on the endocannabinoid system. We talk about CB1 receptors, the endogenous ligands anandamide and 2-AG, and the enzymes involved in making and breaking them down. Dr. Albayram explains that this signaling system is widespread in the brain and is important for neuroimmune regulation and neuronal communication.

We then cover his aging studies in the hippocampus. He reports that endocannabinoid tone declines with age, with reduced 2-AG and related biosynthetic machinery in old hippocampus, without a compensatory increase in receptor expression. He also describes experiments showing that deleting CB1 receptors improves learning in young animals but impairs performance in old animals.

Another key topic is low-dose THC treatment in old mice. He reports that prolonged low-dose THC improved learning and memory in old animals, while reducing performance in young animals. After washout, the older animals still showed improved behavior, along with changes in synaptic proteins and gene expression patterns that shifted toward a younger profile.

We also discuss the epigenetic findings. He says THC increased histone acetylation at promoters of anti-aging genes such as BDNF and Klotho after treatment had ended, suggesting longer-lasting regulation. He is now focusing on GABAergic neurons in the hippocampus to identify the specific epigenetic mechanisms involved and how they may relate to age-dependent neurodegenerative disorders.

References

• Albayram, O., Alferink, J., Pitsch, J., Piyanova, A., Neitzert, K., Poppensieker, K., Mauer, D., Michel, K., Legler, A., Becker, A., Monory, K., Lutz, B., Zimmer, A., & Bilkei-Gorzo, A. (2011). Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging. Proceedings of the National Academy of Sciences of the United States of America, 108(27), 11256–11261. https://doi.org/10.1073/pnas.1016442108

Related Episodes

• Long-Term Maintenance of Neuronal Identity (Tomohisa Toda)
• The Role of Histone Dopaminylation and Serotinylation in Neuronal Plasticity (Ian Maze)
• How BRD4 and H2BE Influence Neuronal Activity (Erica Korb)

Contact

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