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Role of the Endocannabinoid System in Neurogenesis

It was believed that humans did not produce anymore neurons postpartum. But today, that dogma is changing. Research has found that not only do neurons constantly proliferate through one’s life but that cannabinoids have an impact on this process. An exciting new research field: neurogenesis.

What is neurogenesis

Neurogenesis is the process by which neural stem cells(NSCs) create neurons in the body to be used for various functions (i.e. sensory, muscular, memory). To understand neurogenesis , the creation of neurons in the body, the hippocampus must be reviewed. The hippocampus is a structure in the medial aspect of the brain that is responsible for learning, memory, mood, and emotion. However, until recently, it was believed that every person was born with a finite number of neurons that would all eventually die as a person aged. This dogma was wrong.

Research in the last five years has proved that his notion is wrong. That actually, the hippocampus is one of the regions where neurons can be created. That the hippocampus is in fact one of the structures in the brain where neurogenesis takes place postpartum. In fact, as far back as the 1960’s scientist Joseph Altman challenged the dogma that neurogenesis did not occur only before birth. The community was still skeptical. But, not today. Joseph Altman found that neurogenesis can also occur in another brain region, in the adult rat olfactory bulb. Today more structures such as the dentate gyrus have been proven to exhibit neurogenesis in adult rat brains.

How does neurogenesis work

At this moment in time the growing field of neurogenesis is still uncovering the pathways in which neurogenesis works. The overview of neurogenesis is the following: neural cell proliferation (1), differentiation(2), maturation, migration, and integration into the neural network.

Once the neural stem cells generate an adolescent neuron it must differentiate into the type of neuron it is programmed to be such as a sensory neuron, a neuromuscular neuron etc… Then once it matures it will have to migrate to it’s outpost, to carry out its mission. Upon arrival the new neuron needs to be integrated into the surround neural network and this marks a complete neurogenesis of a neuron.

What is the Role of the ECS in neurogenesis

It is known that the ECS is utilized in a retrograde inhibitory role of presynaptic neurons butas seen with neurotransmitters which can have totally different functions depending on where they are in the body, it is important to understand that cannabinoids may also have a different impact in the brain versus the periphery of the body. Research on endocannabinoids role in the CNS have confirmed that cannabinoids do have some control over cellular genesis in the adult brain.

The role of the ECS in neurogenesis can be divided into acute administration and chronic. In the former, it has been studied that acute administration of cannabinoids seem to have no effect on neurogenesis or cellular proliferation in the hippocampus. However, chronic administration of exogenous cannabinoids do have an impact. In 2005 Jiang and company used a potent synthetic cannabinoid called HU-210, a drug that has a high affinity for both CB1 & CB2 receptors. The results of that experiment showed that chronic administration of that potent synthetic cannabinoid enhanced not only survival of the cells but also enhanced proliferation fo neural cells in the rats dentate gyrus.

Another study, conducted by Palazuelos and company in 2012 was similar in design. They used a synthetic CB2 selective agonist called HU-308 which also showed proliferative-enhancing effects in rat brains, which brings scientists in agreement that both CB1 & CB2 receptors have some role in the development and creation of neurons in the brain. However, there is some conflicting research with another potent agonist of CB receptors called WIN55 which showed no results as far as cellular proliferation goes in the dentate gyrus in adult rats. But this agonist reduced the number of immature neurons in adolescent rats. So, in light of this, it can be presumed that the effects of cannabinoid agonists vary.

Can endocannabinoid deficiency affect neurogenesis

For the purpose of determining how an animal may act when it has a deficiency of a molecule or organ or system, scientists will often use agonists to oppose the effects that are normal. In this case, an inverse agonist was used to bind to the CB1 receptor and block it to oppose the effects of endocannabinoids and observe the consequences. What was shown is that acute administration of this inverse agonist, AM251, resulted in an increase in cell proliferation for 24-post treatment in adult rats.

However, this increase reverted to a decrease from 48-hours post administration and onward. Again, suggesting a complex temporal role for cannabinoid signaling. The research showed that chronically the same inverse agonist was found to have no effect on cell proliferation; however it has been shown to block the proliferative-enhancing effect of aerobic exercise, which is well established. Ultimately, more research needs to be conducted because of the complex relationship that multiple cannabinoid receptors have on neurogenesis and given their widely available physiology in the human body.

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