Introduction of Gamma-Aminobutyric Acid into the Bloodstream to Negate NMDA Receptor Hypofunction Induced by Delta 9-Tetrahydrocannabinol

Jebriel Abdul,Max L Yan,Maxwell J Zeggil

doi:10.26685/urncst.175

Abstract

Glutamate is the most abundant neurotransmitter found in the brain, controlling fast signalling throughout all sections and being especially involved in memory recollection and learning. Long-Term Potentiation (LTP) is the strengthening of neural connections through receptor synthesis over consistent usage, first triggered by synapse activation by a small amount of glutamate. However, in heavy (prolonged instance of exposure) and habitual users of cannabis, the effects of LTP are exacerbated by N-methyl-D-Aspartic Acid (NMDA) Receptor Hypofunction (NRHypo) which in turn affects memory, learning, reasoning and other aspects of one’s function. Emerging evidence has associated the inhibition of long-term potentiation by Delta 9-Tetrahydrocannabinol (D9-THC) activating presynaptic Cannabinoid Receptor Type 1 (CB1) receptors to the inhibition of the ability to stop production of glutamate (GLU). An excess of glutamate will overstimulate the postsynaptic NMDA and α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) receptors in the neurons commonly in the hippocampus, basal ganglia, and prefrontal cortex, which allow excessive influx of calcium Ca2+ ions, causing neurotoxic conditions. Glutamate Decarboxylase 67 molecule has been shown bind in high concentrations with GLU and lower the harmful effects of D9-THC on the brain by converting GLU to Gamma-Aminobutyric Acid (GABA), an inhibitory neurotransmitter. GAD67 will be distributed to mice in this proposed experiment and the behaviour of the mice will be monitored. D9-THC affected, D9-THC and GAD67 affected, and normal mice will be subjected to behavioral interaction and maze tests which will show differences in their learning, spatial awareness and orientation, and reasoning abilities. Chemical analysis of cerebral fluid and brain slices will determine chemical concentrations of GAD67 and D9-THC in the brain. Using direct injections into the cerebrospinal fluid (CSF) and bloodstream in mouse models, our aim is to determine the selectivity of the blood brain barrier (BBB) to enzymes such as GAD67 via both channels as well as assess the interaction GAD67 has with cascading neurological effects caused by NRHypo and LTP.

Highlights

Introduction of GammaAminobutyric Acid into the Bloodstream to Negate N-methyl-D-Aspartic Acid (NMDA) Receptor Hypofunction Induced by Delta 9-THCJebriel Abdul, BSc Student [1], Maxwell J
GLU binds to Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) and NMDA receptors (AMPAR and NMDAR) on postsynaptic neurons to induce an action potential by post-synaptic opening of calcium Ca2+ ion channels
If AMPARs and NMDARs are rapidly stimulated in minute amounts, long-term potentiation (LTP) is produced

Summary

Introduction

Introduction of GammaAminobutyric Acid into the Bloodstream to Negate NMDA Receptor Hypofunction Induced by Delta 9-THCJebriel Abdul, BSc Student [1], Maxwell J. Upon the arrival of the action potential at the presynaptic axon terminal, the stored GLU is released into the synapse, which activates receptors on the postsynaptic dendrite. Individual receptors have various effects, such as opening calcium channels to form graded potentials that continue through the dendrite and into the cell body and axon, forming the action potential. GLU binds to AMPA and NMDA receptors (AMPAR and NMDAR) on postsynaptic neurons to induce an action potential by post-synaptic opening of calcium Ca2+ ion channels. As glutamate is not rapidly degraded or recycled by the cells, leftover concentrations in the synapse allow for lower amounts of future glutamate release to trigger NMDAR and AMPAR activation [1, 2]

Objectives

Methods

Results

Conclusion