A mechanism whereby cannabis would affect the plasticity of neural circuits is identified

A study led by Andrés Ozaita, a researcher at the Neuropharmacology Laboratory-Neurophar at UPF, shows how the main psychoactive component of cannabis affects the machinery required to maintain the protein balance in the hippocampus. They have discovered a mechanism whereby the cannabis would affect synaptic plasticity, i.e., the neurons’ ability to respond to stimuli, modifying their connections, which are essential for learning and memory. The study, conducted in rodents, has been published in the journal Biochemical Pharmacology.

Derivatives of the plant Cannabis sativa, cannabis or marijuana, are the most consumed illegal drugs worldwide. Their main psychoactive component, Δ9-tetrahydrocannabinol (THC), affects a variety of brain functions, including cognitive performance.

"Chronic cannabis use is known to cause several changes at the cognitive level", explains Victoria Salgado-Mendialdúa, first author of the article, "we decided to study the hippocampus because it is a key area of the brain for learning and memory, and thus relevant for this detrimental effect of THC", she adds.

The researchers analysed the proteins of hippocampus presenting alterations three hours after administering a dose of THC. Then, through the analysis of networks of interaction, they saw that these proteins were related with proteasome, a protein complex responsible for the degradation of the proteins that are unnecessary, or are damaged, leading to their constant turnover.

"It is plausible that THC may disrupt memory function by reducing proteasome activity, since recent evidence shows that, at the synaptic level, where neurons connect with each other, proteasome activity is necessary at all times to maintain the plasticity of the neural circuits. Adequate protein degradation is as important as the synthesis of new proteins for memory formation", Salgado-Mendialdúa states.

"In this study we have identified for the first time how THC decreases proteasome activity in the hippocampus in mice, which will contribute to the imbalance between the mechanisms of protein synthesis and degradation required for the proper functioning of the synapses. We are currently evaluating the relative relevance of this mechanism in the cellular processes modulated by THC in the brain that contribute to changes in learning and memory", says Andrés Ozaita, who continues "this study fits in with previous ones by our group where we noted that THC increased de novo protein synthesis signals, and as a whole would indicate that THC unbalances protein synthesis/degradation processes at the synaptic level", he concludes.

The study also involved Joaquim Aguirre-Plans, Emre Guney and Baldomero Oliva of the Structural Bioinformatics research group of the Research Programme in Biomedical Informatics (GRIB), a joint programme of the Department of Experimental and Health Sciences (DCEXS) and Hospital del Mar Research Medical Institute (IMIM), Rafael Maldonado, director of UPF’s Neuropharmacology Laboratory-NeuroPhar, and Rita Reig-Viader and Àlex Bayés of the Sant Pau Institute of Biomedical Research (IIB Sant Pau) and the Autonomous University of Barcelona (UAB).

Here you can consult the supplementary material and take an interactive look at the results of the article.

Reference article:

Salgado-Mendialdúa, V., Delta9-tetrahydrocannabinol modulates the proteasome system in the Brain. Biochemical Pharmacology (2018), https://doi.org/10.1016/j.bcp.2018.08.026.