Version 1
: Received: 30 April 2024 / Approved: 30 April 2024 / Online: 30 April 2024 (11:49:10 CEST)
How to cite:
Gujar, V.; Pande, R. D.; Hardas, B. M.; Das, S. Nerve Growth Factor Signaling Modulates the Expression of Glutaminase in Dorsal Root Ganglion Neurons during Peripheral Inflammation. Preprints2024, 2024041986. https://doi.org/10.20944/preprints202404.1986.v1
Gujar, V.; Pande, R. D.; Hardas, B. M.; Das, S. Nerve Growth Factor Signaling Modulates the Expression of Glutaminase in Dorsal Root Ganglion Neurons during Peripheral Inflammation. Preprints 2024, 2024041986. https://doi.org/10.20944/preprints202404.1986.v1
Gujar, V.; Pande, R. D.; Hardas, B. M.; Das, S. Nerve Growth Factor Signaling Modulates the Expression of Glutaminase in Dorsal Root Ganglion Neurons during Peripheral Inflammation. Preprints2024, 2024041986. https://doi.org/10.20944/preprints202404.1986.v1
APA Style
Gujar, V., Pande, R. D., Hardas, B. M., & Das, S. (2024). Nerve Growth Factor Signaling Modulates the Expression of Glutaminase in Dorsal Root Ganglion Neurons during Peripheral Inflammation. Preprints. https://doi.org/10.20944/preprints202404.1986.v1
Chicago/Turabian Style
Gujar, V., Bhalchandra M Hardas and Subhas Das. 2024 "Nerve Growth Factor Signaling Modulates the Expression of Glutaminase in Dorsal Root Ganglion Neurons during Peripheral Inflammation" Preprints. https://doi.org/10.20944/preprints202404.1986.v1
Abstract
Glutamate functions as the major excitatory neurotransmitter for primary sensory neurons and has a crucial role in sensitizing peripheral nociceptor terminals producing sensitization. Glutaminase (GLS) is the synthetic enzyme that converts glutamine to glutamate. GLS-immunoreactivity (-ir) and enzyme activity are elevated in dorsal root ganglion (DRG) neuronal cell bodies during chronic peripheral inflammation, but the mechanism for this GLS elevation is yet to be fully characterized. It has been well established that, after nerve growth factor (NGF) binds to its high-affinity receptor tropomyosin receptor kinase A (TrkA), a retrograde signaling endosome is formed. This endosome contains the late endosomal marker Rab7GTPase and is retrogradely transported via axons to the cell soma located in DRG. This complex is responsible for regulating the transcription of several critical nociceptive genes. Here, we show that this retrograde NGF signaling mediates the expression of GLS in DRG neurons during the process of peripheral inflammation. We disrupted the normal NGF/TrkA signaling in adjuvant-induced arthritic (AIA) Sprague Dawley rats by pharmacological inhibition of TrkA or blockade of Rab7GTPase, which significantly attenuated the expression of GLS in DRG cell bodies. These results indicate that NGF/TrkA signaling is crucial for the production of glutamate and has a vital role in the development of neurogenic inflammation. In addition, our pain behavioural data suggest that Rab7GTPase can be a potential target for attenuating peripheral inflammatory pain.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
