Effects of pituitary adenylate cyclase-activating polypeptide on facial nerve recovery in the Guinea pig.
OBJECTIVE
Pituitary adenylate cyclase-activating polypeptide (PACAP) has neurotrophic effects of neural regeneration and gives protection to the nervous system. We investigated whether PACAP had a neurotrophic effect on peripheral motoneurons and whether PACAP could facilitate glial cell line-derived neurotrophic factor (GDNF), a neurotrophin, in nerve regeneration. The presence and distribution of PACAP receptors following facial nerve transection were also investigated.


METHODS
Animal experiment.


METHODS
Unilateral transection of the facial nerve was performed in male Hartley guinea pigs, and PACAP was injected at the site. Saline was substituted as a control. Compound muscle action potentials were recorded to measure the changes of latency. Glial cell line-derived neurotrophic factor (GDNF) content in facial target muscle was measured using enzyme-linked immunosorbent assay. The regenerating site was taken for histological studies.


RESULTS
Pituitary adenylate cyclase-activating polypeptide hastened the appearance of compound muscle action potentials and shortened the latency. Pituitary adenylate cyclase-activating polypeptide increased and prolonged the nerve transection-induced GDNF increase in the facial muscles. The number of myelinated fibers at 1 to 4 weeks after the transection was increased. PAC1 receptor or VPAC1 receptor or both were identified in the injury area at 2 to 4 weeks.


CONCLUSIONS
Pituitary adenylate cyclase-activating polypeptide facilitated the recovery of latency of compound muscle action potentials or the number of myelinated axons, or both. Pituitary adenylate cyclase-activating polypeptide prolonged the GDNF levels in target organs. These data indicated that PACAP promoted regeneration of the facial nerve.
Kimura
Hiromoto
H
Department of Otolaryngology, Akita University School of Medicine, Japan. hkimura@med.akita-u.ac.jp
Kawatani
Masahito
M
Ito
Eiko
E
Ishikawa
Kazuo
K
D000818:Animals; D004558:Electric Stimulation; D004576:Electromyography / Q000187:drug effects; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005152:Facial Muscles / Q000294:innervation; D005154:Facial Nerve / Q000187:drug effects / Q000503:physiopathology; D020220:Facial Nerve Injuries / Q000473:pathology / Q000503:physiopathology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006168:Guinea Pigs; D008297:Male; D009414:Nerve Growth Factors / Q000032:analysis; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000032:analysis; D018005:Receptors, Vasoactive Intestinal Peptide / Q000032:analysis; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D013268:Stimulation, Chemical
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I