Axotomy‐induced changes in pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP receptor gene expression in the adult rat facial motor nucleus

Abstract

It has been demonstrated that pituitary adenylate cyclase activating polypeptide (PACAP) promotes the survival of neurons in culture and can inhibit neuronal cell death after experimental injury. Furthermore, peripheral axotomy results in increased PACAP gene expression in sensory and sympathetic neurons, suggesting that PACAP might be a mediator in the injury response in certain parts of the nervous system. However, changes in PACAP expression have not been reported in injured motor neurons, despite the significant problem of motor neuron degeneration in injury and in several neurological diseases. We examined here changes in gene expression of PACAP and two high-affinity PACAP receptors, PAC(1) and VPAC(2), in adult rat motor neurons after facial nerve axotomy by in situ hybridization. PACAP gene expression was very low in facial motor neurons of normal rats. However, a robust time-dependent increase in PACAP mRNA was observed in the facial motor nucleus in most or all axotomized motor neurons. This induction was detectable 6 hr after axotomy, and peaked at 48 hr, when expression on the injured side averaged more than 20-fold higher than that on the contralateral side. Thereafter, PACAP mRNA levels decreased slightly, but remained more than 10-fold elevated for as long as 30 days after axotomy. In contrast to PACAP, gene expression for both the PAC(1) and VPAC(2) receptor was high in facial motor neurons of normal rats. No significant change was observed for VPAC(2) receptor gene expression in facial motor neurons after axotomy, whereas gene expression for the PAC(1) receptor became significantly decreased. The results indicate that the PACAP ligand receptor system is tightly regulated in the facial motor nucleus after axotomy, providing evidence that PACAP may be involved in motor injury responses.

The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion

“…Although the exact mechanism of these changes is not known yet, it can be suggested that PACAP increased due to its protective effect. Similar upregulation of PACAP has been found earlier in response to other insults [42,52]. The longer and more expressed increase of pacap in the medulla may explain the higher resistance against ischemia.…”

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…In the same way, PACAP increases neuronal survival after spinal cord compression (Chen and Tzeng, 2005), suggesting that PACAP could have beneficial effects in tissue restoration after nerve injury. Consistent with this hypothesis, PACAP and PAC1-R mRNAs are up-regulated for as long as 30 days after facial motor neuron axotomy (Zhou et al, 1999b) and nerve regeneration is impaired in PACAP(Ϫ/Ϫ) animals (Armstrong et al, 2008).…”

“…In the retina, type I PACAP binding sites predominate, whereas in the choroid, both type I and II PACAP binding sites are expressed (Nilsson, 1994;D'Agata and Cavallaro, 1998). Immunocytochemical and Zhou et al, 1999bZhou et al, , 2001 The symbols provide a semi-quantitative evaluation of the density of PAC1-R, VPAC1-R, and VPAC2-R mRNA: ϩϩϩ, high density; ϩϩ, moderate density; ϩ, low density; -, no hybridization.…”

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).…”