COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT (CART) IMMUNOREACTIVITY IN THE HUMAN CERVICAL SPINAL CORD: IMPLICATIONS FOR SPINAL EXCITABILITY

Spinal cord excitability arises from dynamic interactions among neurotransmitters, neuropeptides, and ion channels, particularly Na⁺, K⁺, and Ca²⁺ channels. The biological activity of cocaine-and amphetamine-regulated transcript (CART) has been shown to involve Ca²⁺-dependent mechanisms. Although CART expression is widely documented in experimental animals, human nervous system distribution data remain limited. In this study, we characterized the distribution and morphology of CART-immunoreactive (CART-IR) neurons in human cervical spinal cord segments (C1-C7), focusing on spinal regions previously reported to exhibit high densities of Na⁺ and Ca²⁺ channel expression. Transverse sections were processed for CART immunohistochemistry and quantitatively analyzed using ImageJ. Within gray matter, dense populations of CART-IR were detected in laminae VII, VIII, and IX, and around the central canal. A posterior-to-anterior density gradient was identified, characterized by minimal immunoreactivity in laminae I–II and higher densities in ventral laminae. This gradient is anatomically consistent with previously described organizational principles of the spinal cord, in which dorsal laminae are primarily associated with sensory processing, whereas ventral laminae contain higher densities of modulatory and motor-related neuronal populations. Given prior evidence that CART signaling can influence intracellular Ca²⁺ dynamics and neuronal depolarization, the present findings support a potential role for CART in the modulation of spinal cord excitability through intracellular Ca²⁺ dynamics and neuronal activity. In conclusion, these preliminary observations in the human cervical spinal cord suggest CART-IR neurons may contribute to excitability regulation, highlighting a previously unexplored link between neuropeptidergic signaling and ionic regulatory mechanisms in the human spinal cord.