Cocaine and amphetamine-regulated transcript (CART) is expressed in spino-thalamic projection neurons

Authors

• MJ Iadarola
• AK Sharma
• G Serrano-Berrios
• MR Sapio
• ML Weiss
• DM King
• D Maric
• ES Staedtler
• MC Kelly
• J Singh
• AJ Mannes

Abstract

The spinal cord is a vital part of the central nervous system that connects the brain to the rest of the body and is surrounded by cerebrospinal fluid. It plays a vital role in transmitting sensory and motor signals between the brain and body. Within this network, there are spinal projection neurons, which transmit signals over long distances. These neurons send their axons from the spinal cord to the brain, enabling communication between different parts of the nervous system. Neurons communicate with each other by releasing neurotransmitters and neuropeptides. One of the neuropeptides is known as Cocaine and Amphetamine Regulated Transcript (CARTPT), and it stands out in a specific set of spinal cord neurons. Using custom high-density Xenium in situ hybridization, we identified CARTPT in large neurons in the “marginal zone” of the dorsal horn which are nociceptive specific. This transcript is uniquely expressed in human marginal zone neurons which also express the mu-opioid receptor, OPRM1, suggesting that inhibition of them can contribute to opioid analgesia. Additionally, two other neuropeptides, CCK and substance P (TAC1), are expressed in these glutamatergic neurons. These transcripts were demonstrated with both the Xenium technique and the RNA Scope in situ hybridization method. The CART peptide is known to have implications for dealing with pain. Therefore, understanding CART’s role in the spinal cord is crucial for future developments of treatments that will target pain pathways. Overall, the data suggest novel ways to efficiently inhibit pain signaling in the spinal cord.

Scientific Focus Area: Neuroscience

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