BDNF and endocannabinoids in brain development: neuronal commitment, migration, and synaptogenesis

Abstract Brain derived growth factor (BDNF) and its receptor, Trk B, play major roles in many aspects of brain development. Many reports indicate that BDNF is important in axon specification. It also serves as a survival factor during early development. BDNF can be secreted from both pre- and postsynaptic membranes. When it is taken up by presynaptic axons with its receptor, Trk B, into endosomes, the endosomes are activated to signal. Once BDNF and Trk B reach the cell nucleus, genes involved in development and survival are activated. BDNF plays a key role in specifying column formation in the visual cortex, which is necessary for proper vision to occur. BDNF is also required in both phases of long-term potentiation, which are crucial for memory consolidation. Marijuana and its derivatives contain molecules that function through binding to two G-protein coupled receptors: CB1 and 2. A great quantity of CB1 is expressed in all portions of the brain. These receptors bind to two endocannabinoids (eCBs), amantidine, and 2-arachidonoyl glycerol. Binding of a neurotransmitter to its receptor on the postsynaptic ending of either excitatory or inhibitory neurons triggers the cleavage of a phospholipid to release either amantidine or 2-arachidonoyl glycerol. After eCB binding to its receptor, the presynaptic neuron is inhibited from further neurotransmitter release. eCBs and their receptors, CB1 and 2, play important roles in the specification of neurons during early development. They also serve to guide neurite growth. ECBs and CB1 and 2 are involved in the final specification of synapses. Finally, eCBs and CB1 and 2 function as yin to BDNF and Trk B’s yang. In other words, BDNF release from the postsynaptic terminals triggers neurotransmitter release while eCB release inhibits it.