Receptor protein tyrosine phosphatase sigma inhibits axon regrowth in the adult injured CNS.
Recently, receptor protein tyrosine phosphatase-sigma (RPTPsigma) has been shown to inhibit axon regeneration in injured peripheral nerves. Unlike the peripheral nervous system (PNS), central nervous system (CNS) neurons fail to regenerate their axons after injury or in disease. In order to assess the role of RPTPsigma in CNS regeneration, we used the retinocollicular system of adult mice lacking RPTPsigma to evaluate retinal ganglion cell (RGC) axon regrowth after optic nerve lesion. Quantitative analysis demonstrated a significant increase in the number of RGC axons that crossed the glial scar and extended distally in optic nerves from RPTPsigma (-/-) mice compared to wild-type littermate controls. Although we found that RPTPsigma is expressed by adult RGCs in wild-type mice, the retinas and optic nerves of adult RPTPsigma (-/-) mice showed no histological defects. Furthermore, the time-course of RGC death after nerve lesion was not different between knockout and wild-type animals. Thus, enhanced axon regrowth in the absence of RPTPsigma could not be attributed to developmental defects or increased neuronal survival. Finally, we show constitutively elevated activity of mitogen-activated protein kinase (MAPK) and Akt kinase in adult RPTPsigma (-/-) mice retinas, suggesting that these signaling pathways may contribute to promoting RGC axon regrowth following traumatic nerve injury. Our results support a model in which RPTPsigma inhibits axon regeneration in the adult injured CNS.
Sapieha
Przemyslaw S
PS
Department of Pathology and Cell Biology, Université de Montréal, 2900, Boulevard Edouard-Montpetit, Pavillon Principal, Room N-535, Montreal, Quebec, Canada H3T 1J4.
Duplan
Laure
L
Uetani
Noriko
N
Joly
Sandrine
S
Tremblay
Michel L
ML
Kennedy
Timothy E
TE
Di Polo
Adriana
A
D000818:Animals; D001369:Axons / Q000502:physiology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D020221:Optic Nerve Injuries / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000235:genetics; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D012165:Retinal Ganglion Cells / Q000502:physiology
D017027:Protein Tyrosine Phosphatases; C516885:Ptprs protein, mouse; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2