Early Alterations of PACAP and VIP Expression in the Female Rat Brain Following Spinal Cord Injury

J Mol Neurosci. 2023 Oct;73(9-10):724-737. doi: 10.1007/s12031-023-02151-w. Epub 2023 Aug 30.

Abstract

Previous evidence shows that rapid changes occur in the brain following spinal cord injury (SCI). Here, we interrogated the expression of the neuropeptides pituitary adenylyl cyclase-activating peptide (PACAP), vasoactive intestinal peptides (VIP), and their binding receptors in the rat brain 24 h following SCI. Female Sprague-Dawley rats underwent thoracic laminectomy; half of the rats received a mild contusion injury at the level of the T10 vertebrate (SCI group); the other half underwent sham surgery (sham group). Twenty-four hours post-surgery, the hypothalamus, thalamus, amygdala, hippocampus (dorsal and ventral), prefrontal cortex, and periaqueductal gray were collected. PACAP, VIP, PAC1, VPAC1, and VPAC2 mRNA and protein levels were measured by real-time quantitative polymerase chain reaction and Western blot. In SCI rats, PACAP expression was increased in the hypothalamus (104-141% vs sham) and amygdala (138-350%), but downregulated in the thalamus (35-95%) and periaqueductal gray (58-68%). VIP expression was increased only in the thalamus (175-385%), with a reduction in the amygdala (51-68%), hippocampus (40-75%), and periaqueductal gray (74-76%). The expression of the PAC1 receptor was the least disturbed by SCI, with decrease expression in the ventral hippocampus (63-68%) only. The expression levels of VPAC1 and VPAC2 receptors were globally reduced, with more prominent reductions of VPAC1 vs VPAC2 in the amygdala (21-70%) and ventral hippocampus (72-75%). In addition, VPAC1 downregulation also extended to the dorsal hippocampus (69-70%). These findings demonstrate that as early as 24 h post-SCI, there are region-specific disruptions of PACAP, VIP, and related receptor transcript and protein levels in supraspinal regions controlling higher cognitive functions.

Keywords: Central nervous system (CNS); Pituitary adenylate cyclase-activating polypeptide (PACAP); Spinal cord injury (SCI); Vasoactive intestinal peptide (VIP).

MeSH terms

  • Animals
  • Brain / metabolism
  • Female
  • Pituitary Adenylate Cyclase-Activating Polypeptide / genetics
  • Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / genetics
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / metabolism
  • Receptors, Pituitary Hormone* / genetics
  • Receptors, Pituitary Hormone* / metabolism
  • Receptors, Vasoactive Intestinal Peptide, Type II / genetics
  • Receptors, Vasoactive Intestinal Peptide, Type II / metabolism
  • Receptors, Vasoactive Intestinal Polypeptide, Type I / genetics
  • Receptors, Vasoactive Intestinal Polypeptide, Type I / metabolism
  • Spinal Cord Injuries* / metabolism
  • Vasoactive Intestinal Peptide / genetics
  • Vasoactive Intestinal Peptide / metabolism

Substances

  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Hormone
  • Vasoactive Intestinal Peptide
  • Receptors, Vasoactive Intestinal Polypeptide, Type I
  • Receptors, Vasoactive Intestinal Peptide, Type II
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I