Abstract
The present research has reported that cannabinoid receptor 1 (CB1) agonist, delta-(9)-tetrahydrocannabinol (THC) modulates synaptogenesis during overexcitation. Microtubule and synaptic distribution, poly(ADP)-ribose (PAR) accumulation were estimated during overexcitation and in the presence of THC. Low concentration of THC (10 nM) increased synaptophysin expression and neurite length, while high concentration of THC (1 µM) induced neurotoxicity. Glutamate caused the loss of neurons, reducing the number and the length of neurites. The high concentration of THC in the presence of glutamate caused the PAR accumulation in the condensed nuclei. Glutamate upregulated genes that are involved in synaptogenesis and excitatory signal cascade. Glutamate downregulated transcription of beta3 tubulin and microtubule-associated protein 2. THC partially regulated gene expression that is implicated in the neurogenesis and excitatory pathways. This suggests that CB1 receptors play a role in neurite growth and the low concentration of THC protects neurons during overexcitation, whereas the high concentration of THC enhances the neurotoxicity.
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Acknowledgements
Many thanks to Dr. D. L. Feinstein for permission to do some research in his laboratory, Dr. M. Sceniak for editing and making some comments and Dr. D. P. Gavin for supervision of this research work and financial support. This work was supported by a grant from a Research Career Scientist award from the Department of Veterans Affairs.
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Savchenko, V.L. Modulation of Excitatory Synaptic Transmission During Cannabinoid Receptor Activation. Cell Mol Neurobiol 42, 1933–1947 (2022). https://doi.org/10.1007/s10571-021-01074-7
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DOI: https://doi.org/10.1007/s10571-021-01074-7