Increased levels of the body’s own cannabinoids impair embryonic brain development.

JZL184 induces growth cone repulsion via ​Slit2/​Robo1 signalling. (a) Neurites (arrowheads) contacting oligodendrocytes when co-cultured. (b) Neurites (open arrowheads) excluded from the vicinity of oligodendrocytes upon ​JZL184 application. Note the intensely ​Slit2+ peripheral domain of the oligodendrocyte (Olig) shown. Endocannabinoids modulate cortical development by configuring Slit2/Robo1 signalling. Harkany et al 2014.

The human body produces substances, called endocannabinoids, that work in a similar way to cannabis. These endocannabinoids may not produce a ‘high’, but are of tremendous importance for the functioning of the neural network in the brain, especially during the embryonic stage. If this network is interfered with as a result of too many circulating endocannabinoids, the development of the embryonic brain can be impaired. Researchers at the Medical University of Vienna have now discovered what mechanism underlies the development of this impairment. 

The protein Slit and its receptor Robo (roundabout) are important signalling molecules in the developing brain. Slits can regulate directional guidance of nerve cell processes (called axons), by binding to Robo receptors, directing the formation of embryonic brain circuitry. The team have now shown that endocannabinoids can regulate Slit and Robo levels in both nerve cells and oligodendrocytes, which support nerve cells, through cannabinoid receptors CB1 and CB2.

This signalling system is important for correct embryonic brain development. If this system goes haywire due to increased levels of endocannabinoids, a kind of stimulation storm occurs.  In this case, both Slit and Robo are produced in greater quantities, leading to changes in axonal guidance decisions. If the endocannabinoid system is in balance, however, this type of over-stimulation does not occur.

The researchers also found this signalling system, and its regulation by cannabinoids, in human embryonic brains. Since, increased endocannabinoid levels are found in metabolic syndromes such as obesity and insulin resistance, as well as during maternal infections, it is important to normalize altered endocannabinoid levels during pregnancy to ensure correct embryonic brain development.  The group have demonstrated that the body’s own cannabinoids are able to regulate an important signalling system in the development of embryonic brain circuitry.

Source:  The Medical University of Vienna’s Centre for Brain Research

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