Cannabinoids and cellular fate in the brain

Cannabinoids

Cannabinoids and cellular fate in the brain

 

Decisions on the cellular destiny are key for the correct maintenance of the cellular environment as well as for the survival of tissues and organisms. The endocannabinoid system is an important regulator of determining the fate of brain cells under normal and pathological conditions.

During embryonic development, from a single cell (the zygote) the rest of the different cells that form an organism are formed. A stem cell gives rise to two daughter cells that undergo different processes that include migration to the area of ​​the body where they are necessary, proliferation or differentiation in a characteristic way (neurons, red blood cells, skin cells …) up to reach your cell destiny where it will develop its specific functions. Other cells, on the other hand, will not be necessary and will suffer a controlled death. This also occurs during the development of the individual and during the regeneration of tissues. To maintain the proper functioning of cells and tissues, this process has to be strongly regulated, otherwise, it may lead to uncontrolled cell growth, which is what occurs in cancer, or death unwanted cell, as occurs in some diseases such as Parkinson’s or Alzheimer’s. CBD TINCTURES

Among the factors that regulate cell fate are some endogenous factors such as cellular microenvironment, epigenetic factors, or remote or external signals. Among these factors are the signaling pathways associated with the endocannabinoid system, especially relevant in the development of the nervous system and in the adult brain, where they can promote the survival of different “non-transformed” brain cells (neurons, astrocytes, oligodendrocytes, ..) or they can have a pro- or anti-tumor effect on cancer cells (“transformed”).

 

Effect of cannabinoids on brain development

The endocannabinoid system is gift from the first stages of embryonic development. In them, the cannabinoid CB1 receptor plays a fundamental role in regulating the normal growth of the embryo. On the other hand, the CB2 receptor appears to be responsible for controlling the population of stem cells, which are those undifferentiated cells, with the capacity to renew themselves and with the potential to become different types of cells. Buy Dank Vapes online

In recent years, more and more evidence has been gathered of the role that the endocannabinoid system plays in the development of the immature brain. Stem cells from the brain (called neural progenitors) are capable of producing the two main endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The CB1 receptor is expressed from the early stages of embryonic development. The levels of this receptor are low and increase during neuronal differentiation. In contrast, the CB2 receptor, which is normally absent in neurons, is present in neural progenitors. Both receptors play a role in regulating the cell fate of these neural progenitors. Activation of both CB1 and CB2 promotes proliferation and increases the number of available neural progenitors. Furthermore, the CB1 receptor regulates the differentiation of these progenitors in both neurons and glial cells (astrocytes and oligodendrocytes) depending on the cellular environment.

In the adult brain there is also formation of new neurons (neurogenesis) in certain areas called neurogenic niches. This is important in the case of brain injuries, in which this neurogenesis is activated and the new neurons are integrated in the affected areas. A malfunction of this process, however, can lead to poor connections between neurons that can cause epilepsy. Thus, regulation of the endocannabinoid system could have therapeutic utility in adult neurogenesis after brain damage. Furthermore, it has been found that neurogenesis in the hippocampus, an area of ​​the brain related to memory, plays an important role in emotional states, and that stimulation of neurogenesis may be useful in the treatment of depression. In this regard, cannabidiol, CBD CREAMS

 

Effect of cannabinoids on neuroprotection

As mentioned above, the dying neurons could be replaced by new neurons, although the way to act on this mechanism is still far from our understanding. That is why to ensure the proper functioning of the brain it is very important to protect the original neurons. The endocannabinoid system has demonstrated both its in vivo and in vitro its neuroprotective potential in non-transformed cells, to the point that it has been considered by some researchers as a defense system of the brain against inflammatory, excitotoxic, infectious, traumatic or oxidative damage. This response of the endocannabinoid system can be imitated by administering compounds that interact with said system, with beneficial results.

Although this neuroprotective potential has long been known, new mechanisms have recently been described by which the endocannabinoid system can protect brain cells. For example, endogenous cannabinoids have been shown to protect neurons from ischemic damage by activating the CB1 receptor in astroglia. The presence of cannabinoid receptors in intracellular compartments, such as the mitochondria, has also been detected, offering a new therapeutic target against mitochondrial dysfunction and oxidative stress, which would be relevant in different neurological pathologies such as Alzheimer’s, Parkinson’s, Huntington’s, lateral sclerosis. amyotrophic, stroke, and neuropsychiatric such as depression, bipolar disorder, and schizophrenia.

Finally, it has recently been seen that the endocannabinoid system can stimulate autophagy in both transformed and non-transformed cells, which can have different effects on each cell type. Autophagy (which means “eating oneself”) is a process by which double-membrane structures enclose part of the interior of the cell and direct it to degradation. It is an evolutionarily conserved process that plays an important role in maintaining homeostasis, the proper functioning of the cell. Autophagy works when the cell does not receive enough nutrients when there are pathogen infections and by removing old proteins, protein aggregates, and damaged organelles. Autophagy failures have been associated with numerous diseases. Dank vapes for sale

 

Effect of cannabinoids on the cellular fate of tumor cells

The effect of cannabinoids on the fate of tumor cells is open to debate in the scientific community since it has been found that activation of the cannabinoid system can have an anti-cancer effect and also an effect on the generation and progression of tumors. Buy cannabis oil online

Cannabinoids can cause death of tumor cells in many ways. The most numerous are those that cause programmed cell death, known as apoptosis, which can be caused, among other mechanisms, by the activation of the CB1 and / or CB2 cannabinoid receptors, by the activation of the TRPV1 vanilloid receptor, by the activation of the receptors PPAR γ , by activation of the GPR55 receptor (considered by some to be the “CB3 receptor”) and even by receptor-independent mechanisms. Cannabinoids can also cause autophagy activation in tumor cells but, unlike what happened in non-transformed cells, where this activation was neuroprotective, in cancer cells causes their death. Buy dank vape carts online

On the other hand, there are authors who have seen that there is an increase in the levels of endocannabinoids and their receptors that is associated with increased tumor aggressiveness. The CB2 receptor has also been described as a proto-oncogene, with a role in the development of different tumors and whose inactivation has an inhibitory effect on tumor growth.

 

Conclusion

Endocannabinoid-mediated signaling controls the proliferation, differentiation, and death of brain cells, which has important consequences for neural development and brain repair. Maintaining the plasticity and function of brain cells mediated by the endocannabinoid system provides an opportunity for the use of endogenous stem cell-based neurorepair strategies and the various mechanisms by which cannabinoids provide neuroprotection make them very useful tools. interesting for its potential application in various neurodegenerative diseases. On the other hand, the effect of the endocannabinoid system on cell death makes it a promising therapeutic target for the treatment of different brain tumors.

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