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Scientific, Legal, and Regulatory Considerations for Cannabidiol
Published in Robert E.C. Wildman, Richard S. Bruno, Handbook of Nutraceuticals and Functional Foods, 2019
Jay Manfre, Rick Collins, Marielle Kahn Weintraub, Robert E.C. Wildman
Traditional synaptic signaling involves neurotransmitters being released from the presynaptic terminal, then diffusing to the postsynaptic terminal, where they bind and activate receptors. However, the CB1 receptor is theorized to use a less common form of signaling, called retrograde signaling.12 Retrograde signaling occurs when a diffusible messenger is released from the postsynaptic terminal and travels “backward” across the synaptic cleft, where it activates receptors on the presynaptic cell (Figure 8.2).
The Tao of Pain
Published in Peter Wemyss-Gorman, John D Loeser, Pain, Suffering and Healing, 2018
In the mid-1970s a deeper understanding of the cellular mechanisms started to emerge based on the chemistry of the nervous system and the means by which neurons communicated. As a result the neurons are no longer seen as one-way conduits of a message. Intra-neural activity altering the way the signals are transmitted, inhibition, excitation, retrograde signalling across the synapse, and the chemical environment of the cell in the extra-cellular-fluid, have become all part of the new understanding of neural activity. In recent times there has been an explosion of interest in the role of glial cells in the functioning of the neuron and neural transmission. The neuro-chemical network becomes more complex the more we explore it. Therefore trying to explain or predict outcomes from this knowledge becomes even more impossible than before.
Nerve Growth Factor and Its Receptor System in Rheumatologic Diseases and Pain Management
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Smriti K. Raychaudhuri, Siba P. Raychaudhuri
Thus, NGF/NGF-R influences the generation and processing of pain signals in several ways. It is likely that upregulation of NGF occurs as a part of the tissue response to injury or inflammation. NGF activates TrkA receptors on sensory neurons and modifies the function of the TRPV1 channel and axonal sodium channel to enhance pain signal transmission. The NGF/TrkA interaction on sensory neurons initiates retrograde signaling to the cell body of the neurons and induces expression of genes that encode precursors of neuropeptides, which contribute to the long-term sensitization for the pain response. NGF also can degranulate mast cells, and thus has the potential to initiate the inflammatory machinery by upregulating adhesion molecules (ICAM-1), chemokines (RANTES), and cytokines (IL-1 and TNF-α). An inflammatory reaction will induce the release of many other pain mediators to enhance the pain response.
MicroRNA-124 ameliorates autophagic dysregulation in glaucoma via regulation of P2X7-mediated Akt/mTOR signaling
Published in Cutaneous and Ocular Toxicology, 2022
Autophagy is a pivotal intracellular cargo-degradation system that involved lysosomal degradation and clearance of protein aggregates and extraneous organelles6. Especially, neurons are highly susceptible to ageing or stress-related organelle injury leading to autophagic dysfunction6,7. A seminar study by Kleesattel et al. demonstrated that anterograde transport defect is concomitant with aberrantly increased autophagy and cytoskeletal abnormalities in optic nerves8. A repertoire of regulatory molecules including transcription factors as well as circular, small and long noncoding RNAs are involved in the regulation of autophagy in glaucoma9,10. MicroRNAs (miRNAs) are tiny linear noncoding RNAs containing 20 nucleotides that regulate post-transcriptional gene expression. MiRNAs (and also an array of mRNAs and synaptic proteins) present in the neuronal exosomes play a pivotal role in the anterograde/retrograde signalling mechanism across synapses in the nervous system11. Assimilation of microRNAs with gene expression data provides deeper knowledge about the molecular pathogenesis of glaucomatous neurodegeneration mediated through aberrantly elevated IOP12. Hitherto, there is no FDA-approved treatment option for glaucoma other than IOP lowering agents. In the recent years, miRNAs are increasingly explored for the treatment of various neurodegenerative diseases including retinal degenerative diseases13,14.
A reductionist approach to understanding the nervous system: the Harold Atwood legacy
Published in Journal of Neurogenetics, 2018
Jeffrey S. Dason, Marla B. Sokolowski, Chun-Fang Wu
The next six papers are original research reports using the Drosophila larval nmj. Chun-Fang Wu and Xiaomin Xing describe the inter-relationships between physical dimensions, distal-proximal rank orders, and basal GCaMP fluorescence levels in functionally distinct synaptic boutons (Xing & Wu, 2018). Greg Lnenicka et al. examine the effects of parvalbumin on synaptic development and physiology (He, Nitabach, & Lnenicka, 2018). Bryan Stewart et al. report a role for postsynaptic Syntaxin 4 in the negative regulation of presynaptic neurotransmitter release through a retrograde signaling mechanism (Harris, Littleton, & Stewart, 2018). Jeffrey Dason et al. characterize the role of a Type II phosphatidylinositol 4-kinase in synaptic function (Cantarutti, Burgess, Brill, & Dason, 2018). Gregory Macleod et al. describe novel ‘kisser’ probes for resolving the distribution of membrane proteins (Stawarski, Hernandez, Justs, & Macleod, 2018). Ken Dawson-Scully et al. report a role for BK channels in tolerance of synaptic transmission to acute oxidative stress (Bollinger, Sial, & Dawson-Scully, 2018).
Endocannabinoids and addiction memory: Relevance to methamphetamine/morphine abuse
Published in The World Journal of Biological Psychiatry, 2022
Mirmohammadali Mirramezani Alizamini, Yonghui Li, Jian-Jun Zhang, Jing Liang, Abbas Haghparast
Cannabinoid transmission in the mPFC is critically involved in memory processing (Tan et al. 2010). Data show that the endocannabinoid -retrograde signalling plays a prominent role in long-term synaptic plasticity at the excitatory synapses of the PFC (Lafourcade et al. 2007). Also, CB1Rs are expressed within the mammalian mPFC (Oropeza et al. 2007; Fitzgerald et al. 2013). The mPFC is related to associative memory formation between morphine and non-salient cues and relapse in morphine addiction in animal models. Furthermore, it was revealed that protein synthesis in the BLA controls the consolidation of morphine-related memory in mPFC (Gholizadeh et al. 2013).