Effects of p75 neurotrophin receptor knockout on axonal regeneration in a mouse model of facial nerve injury

BACKGROUND:Previous studies have shown that p75 neurotrophin receptor plays an important role in peripheral nerve injury.However,the role of p75 neurotrophin receptor in the regeneration of peripheral nerves remains poorly understood. OBJECTIVE:To study the effect of p75 neurotrophin receptor on facial nerve regeneration. DESIGN,TIME AND SETTING:A randomized controlled experiment was performed in the Regeneration Laboratory of Flinders University,Australia and the Biomedical Laboratory of Dentistry School,Shandong University from March 2005 to February 2006. MATERIALS:Cholera toxin B subunit,fast blue,and biotin rabbit-anti goat IgG were provided by Sigma,USA;goat-anti choleratoxin B subunit antibody was provided by List Biologicals,USA. METHODS:In p75 neurotrophin receptor knockout and wild type 129/sv mice,the facial nerves on one side were crushed.At days 2 and 4 following injury,regenerating motor neurons in the facial nuclei were labeled by fast blue,and the regenerating axon was labeled by the anterograde tracer choleratoxin B subunit. MAIN OUTCOME MEASURES:Axonal regenerative velocity and number were detected by immunohistochemical staining of choleratoxin B subunit,growth-associated protein,protein gene product 9.5,and calcitonin-gene-related peptide;survival of motor neurons in the facial nuclei was detected by retrograde fast blue. RESULTS:Axonal growth in the facial nerve of p75 neurotrophin receptor knockout mice was significantly less than in wild type mice.At day 7 after injury,the number of regenerating motor neurons in p75 neurotrophin receptor knockout mice remained significantly less than in wild type mice(P<0.05).The number of positively stained fibers for growth-associated protein-43,protein gene product 9.5,and calcitonin-gene-related peptide in p75 neurotrophin receptor knockout mice was significantly less than in wild type mice(P<0.01). CONCLUSION:p75 neurotrophin receptor promoted axonal regeneration and enhanced the survival rate of motor neurons following facial nerve injury.