PACAP mRNA is expressed in rat spinal cord neurons

Abstract

This study examines the expression of pituitary adenylate cyclase activating polypeptide (PACAP) mRNA in the rat spinal cord during normal conditions and in response to sciatic nerve transection. Previously, PACAP immunoreactivity has been found in fibers in the spinal cord dorsal horn and around the central canal and in neurons in the intermediolateral column (IML). Furthermore, in the dorsal root ganglia, PACAP immunoreactivity and PACAP mRNA expression have been observed preferentially in nerve cell bodies of smaller diameter terminating in the superficial laminae of the dorsal horn. However, neuronal expression of PACAP mRNA in adult rat spinal cord appeared limited to neurons of the IML. By using a refined in situ hybridization protocol, we now detect PACAP mRNA expression in neurons primarily in laminae I and II, but also in deeper laminae of the spinal cord dorsal horn and around the central canal. In addition, PACAP mRNA expression is observed in a few neurons in the ventral horn. PACAP expression in the ventral horn is increased in a population of large neurons, most likely motor neurons, both after distal and proximal sciatic nerve transection. The proposed role of PACAP in nociception is strengthened by our findings of PACAP mRNA-expressing neurons in the superficial laminae of the dorsal horn. Furthermore, increased expression of PACAP in ventral horn neurons, in response to nerve transection, suggests a role for PACAP in repair/regeneration of motor neurons.

Regulation of neuronal pituitary adenylate cyclase-activating polypeptide expression during culture of guinea-pig cardiac ganglia

“…PACAP peptides are potent trophic molecules and it is commonly proposed that an increased expression of PACAP peptides following injury may support neuronal survival and regeneration (Moller et al, 1997a,b;Zhou et al, 1999;Boeshore et al, 2004;Pettersson et al, 2004). PACAP can protect cardiomyocytes against oxidative stress-induced apoptosis (Gasz et al, 2006).…”

“…In control peripheral nervous system structures, such as parasympathetic and sympathetic ganglia, dorsal root ganglia, vagal sensory ganglia and spinal and cranial motor nuclei, limited numbers of neurons exhibit PACAP immunoreactivity. However, PACAP expression increases markedly in these neurons following axotomy or explant culture (Zhang et al, 1995(Zhang et al, ,1996Moller et al, 1997a,b;Zhou et al, 1999;Pettersson et al, 2004). It is hypothesized that the increased expression of PACAP may be a response to injury that supports cell survival and regeneration (Moller et al, 1997a,b;Armstrong et al, 2003;Boeshore et al, 2004;Pettersson et al, 2004;Suarez et al, 2006).…”

“…However, PACAP expression increases markedly in these neurons following axotomy or explant culture (Zhang et al, 1995(Zhang et al, ,1996Moller et al, 1997a,b;Zhou et al, 1999;Pettersson et al, 2004). It is hypothesized that the increased expression of PACAP may be a response to injury that supports cell survival and regeneration (Moller et al, 1997a,b;Armstrong et al, 2003;Boeshore et al, 2004;Pettersson et al, 2004;Suarez et al, 2006).In acutely isolated guinea pig cardiac ganglia, all the intrinsic neurons are innervated by extrinsic PACAP-IR fibers, but very few of the cardiac neurons exhibit PACAP immunoreactivity Calupca et al, 2000;Parsons et al, 2006). Following explant culture, the extrinsic PACAP-IR fibers degenerate and the percentage of cholinergic neurons expressing PACAP increases significantly (Calupca et al, 2000;Girard et al, 2006b).…”

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

“…The PAC1 receptor is expressed mainly on neural and smooth muscle cells, while the VPAC1/VPAC2 are localized principally on the dorsal root ganglia (DRG), sensory nerve endings, and inflammatory cells [6,9,50,55,64]. The fact, that PACAP shows increased expression in the superficial layer of the spinal dorsal horn and in capsaicin-sensitive primary sensory neurons, suggested that it has a role in nociception [33,34,39,[61][62][63]. However, the results obtained from the early in vivo studies proved to be contradictory [41].…”

Role of pituitary adenylate cyclase-activating polypeptide (pacap) in the trigeminovascular system: preclinical and clinical results

“…The fact that systemic administration of PACAP can evoke sensitization and migraine-like attacks in migraineurs [27] is in line with the results of our animal experiments. Moreover, PACAP release in the dorsal horn has been reported in other experimental conditions of peripheral stimulation [126][127][128][129][130]. The potential relationship between PACAP and pain is enhanced by the co-localization and functional link of the NOS and PACAP systems, which has been described in a variety of studies [63,76,[131][132][133][134].…”