Disruption of the midkine gene (Mdk) delays degeneration and regeneration in injured peripheral nerve.
Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. MK acts as a reparative neurotrophic factor in damaged peripheral nerves. A postulated role of MK in the degeneration and regeneration of sciatic nerves was explored by comparing wild-type (Mdk(+/+)) mice with MK-deficient (Mdk(-/-)) mice after freezing injury. In the Mdk(-/-) mice, a regenerative delay was observed, preceded by a decelerated Wallerian degeneration (WD). The relative wet weight of the soleus muscle slowly declined, and recovery was delayed compared with that in the Mdk(+/+) mice. In the regenerating nerve, unmyelinated axons were unevenly distributed, and some axons contained myelin-like, concentrically lamellated bodies. In the endplates of soleus muscles, nerve terminals containing synaptic vesicles disappeared in both mice. In Mdk(-/-) mice, the appearance of nerve terminals was delayed in synaptic vesicles of terminal buttons after injury. The recovery of evoked electromyogram was delayed in Mdk(-/-) mice compared with Mdk(+/+) mice. Our results suggested a delay in axonal degeneration and regeneration in Mdk(-/-) mice compared with Mdk(+/+) mice, and the delayed regeneration was associated with a delayed recovery of motor function. These findings show that a lack of MK following peripheral nerve injury is a critical factor in degeneration and regeneration, and manipulation of the supply of MK may offer interesting therapeutic options for the treatment of peripheral nerve damage.
Sakakima
Harutoshi
H
School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. sakaki@health.nop.kagoshima-u.ac.jp
Yoshida
Yoshihiro
Y
Yamazaki
Yoshiki
Y
Matsuda
Fumiyo
F
Ikutomo
Masako
M
Ijiri
Kosei
K
Muramatsu
Hisako
H
Muramatsu
Takashi
T
Kadomatsu
Kenji
K
D000818:Animals; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004576:Electromyography; D005615:Freezing; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000078792:Midkine; D009045:Motor Endplate / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D020127:Recovery of Function; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism; D014855:Wallerian Degeneration / Q000235:genetics / Q000503:physiopathology*
D016207:Cytokines; D000078792:Midkine