Tuesday, April 3, 2018

Study Suggests Cannabinoids May Improve Muscle Function In Myasthenia Gravis

The muscle function in a study using a mouse model of myasthenia gravis was improved after treatment with cannabinoids improved, suggesting they may have therapeutic potential for the disease, researchers say.

The study, “Cannabinoid-induced increase of quantal size and enhanced neuromuscular transmission,” was published in the journal Scientific Reports.

By Jose Marques Lopes, PhD

Multiple levels of neuronal communication, including the formation of new neurons and the release of neurotransmitters, are regulated by cannabinoids which act as chemical couriers that enable good neuron-to-neuron communication.

Most research on cannabinoids has been limited to studies of changes within the brain, while their effects on the neuromuscular junction (NMJ) —the connection between a motor neuron and a muscle cell — have been ignored by the scientific community.

In the past, animal studies  have revealed that, very much like to their effects on the brain, specific cannabinoids act on the NMJ to reduce the amount of released vesicles per nerve impulse, in a process referred to as quantal content. Vesicles are tiny structures that contain neurotransmitters that are released from neuron to neuron.

It should be noted that, aside from findings in rats with regards to delta9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, researchers have yet to find information on the action of cannabinoids at the mammalian NMJ.

The objective of the research team is to fill this gap in knowledge by determining the function of cannabinoids at the NMJ. Because the use of cannabinoids in medical practice is increasing, understanding their influence on the peripheral nervous system “might have broad implications for the therapeutic application of cannabinoids,” they wrote.

Generally the action of Cannabinoids is through cannabinoid-1 (CB1) receptors, which are found in abundance throughout the central nervous system (CNS), but have developed at lower levels outside the brain and spinal cord. CB1 receptors regulate the release of two main neurotransmitters — GABA, which is inhibitory, and glutamate, which is excitatory — as well as other molecules such as acetylcholine, noradrenaline, dopamine, and opioids.

With the use of mice, the results showed that cannabinoids have a different effect at the mammalian NMJ than in the brain. Cannabinoids increased synaptic vesicle volume and the content of acetylcholine within each vesicle, which led to a boost in neuromuscular transmission.

These results differ from cannabinoids’ effects at CNS synapses, where these molecules typically reduce the release of vesicles, the authors said.

Data also revealed that the molecular pathways activated by cannabinoids in the NMJ are different from those in the CNS. Further research is needed to identify which cannabinoids improve neuromuscular transmission and which receptors are involved, the team said.

Researchers also found that treatment with a cannabinoid receptor agonist (WIN 55,212) restored neuromuscular transmission in the MG mice.

“Our data suggest an endogenous pathway by which cannabinoids might help to regulate transmitter release at the [NMJ],” the investigators wrote. The study also highlights a “possible therapeutic potential for cannabinoid signaling in [MG],” they said.

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