Neurotransmitters, also known as chemical messengers produced naturally by the body, endogenous cannabinoids, or endocannabinoids, transmit specific signals from one neuron to another. It is known that these neurotransmitters support a number of essential physiological processes, such as sleep, mood, and appetite.
Endocannabinoids’ functions have been the subject of numerous studies, but the mechanisms by which they are released are still poorly understood. Postsynaptic synucleins, proteins that have been linked to the development of Parkinson’s disease, were the subject of a recent Stanford University study that was recently published in Nature Neuroscience. The study gathered evidence that supports the release of these essential neurotransmitters.
Eddy Albarran, Yue Sun, and their colleagues wrote in their paper, “Endocannabinoids are among the most powerful modulators of synaptic transmission throughout the nervous system, but little is known about the release of endocannabinoids from postsynaptic compartments.” We report a surprising discovery: that endocannabinoid discharge requires synucleins, key supporters of Parkinson’s infection.”
“Endocannabinoids are among the most powerful modulators of synaptic transmission throughout the nervous system, but little is known about endocannabinoid release from postsynaptic compartments,”
Eddy Albarran, Yue Sun, and their colleagues wrote in their paper.
Synucleins, also known as -synuclein (-Syn), -synuclein (-Syn), and -synuclein (-Syn), are small, soluble proteins that are expressed in the brain tissue of vertebrates. It is known that synucleins are involved in synaptic plasticity, which is the brain’s capacity to alter the strength of its connections and adapt over time. A-Synuclein (a-Syn) mutations have been linked to early-onset Parkinson’s disease and abnormal protein accumulation in patients with Parkinson’s, Alzheimer’s, and other neurodegenerative diseases, according to previous neuroscience research.
When Albarran, Sun, and their colleagues set out to learn more about how the brain regulates the release of endocannabinoids, they were surprised to find that synucleins supported this. A variety of genetic and imaging procedures were used in their experiments, which were carried out on mice.
Albarran, Sun, and their colleagues explained, “We show that endocannabinoids are released postsynaptically by a synuclein-dependent and SNARE-dependent mechanism.” Particularly, we discovered that synuclein deletion inhibits synaptic plasticity dependent on endocannabinoids; Postsynaptic expression of wild-type but not mutant synuclein reverses this block. The synuclein deletion specifically inhibits endocannabinoid release, according to whole-cell recordings and direct optical monitoring of endocannabinoid signaling.
Given that previous research had suggested that there was no connection between SNARE proteins and the release of endocannabinoids, the findings that this team of researchers gathered were extremely surprising. In the end, their research suggests that endocannabinoid signaling in the brain may be associated with Parkinson’s disease and other neurodegenerative conditions.
This study may pave the way for additional research into this connection in the future, potentially leading to significant discoveries. As a result, new medications and therapeutic approaches to treat these diseases’ debilitating symptoms may be developed.
“We hypothesize that endocannabinoids are released via a membrane interaction mechanism, given the presynaptic role of synucleins in regulating the vesicle lifecycle,” the researchers wrote. Postsynaptic expression of the tetanus toxin light chain, which cleaves synaptobrevin SNAREs, also prevents endocannabinoid-dependent signaling, which is consistent with this hypothesis. The unexpected discovery that endocannabinoids are released through a synuclein-dependent mechanism contributes to the long-standing puzzle of how neurons release endocannabinoids to induce synaptic plasticity and is consistent with a general function of synucleins in membrane trafficking.”
More information: Eddy Albarran et al, Postsynaptic synucleins mediate endocannabinoid signaling, Nature Neuroscience (2023). DOI: 10.1038/s41593-023-01345-0
