Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration

Although pigment epithelium-derived factor (PEDF) is a neurotrophic factor that may aid the development, differentiation, and survival of adjacent neu ral retinae, the wider distribution of PEDF mRNA in the central nervous sys tem suggested to us that this factor could have pleiotropic neurotrophic an d neuroprotective effects on nonretinal neurons. We examined the distributi on of PEDF mRNA and its transcript in the spinal cord. By immunohistochemis try and western blot analysis using an antihuman PEDF antiserum of known sp ecificity, we found that PEDF protein is present in spinal cord, cerebrospi nal fluid, and skeletal muscle and that its mRNA appears concentrated in mo tor neurons of the human spinal cord. These observations indicate that PEDF could have potential autocrine and paracrine effects on motor neurons, as well as being target-derived. We analyzed the pharmacologic utility of PEDF in a postnatal organotypic culture model of motor neuron degeneration and proved it is highly neuroprotective. The effect was biologically important, significantly sparing the spinal cord's gross organotypic morphological ap pearance and preserving motor neuron choline acetyltransferase (ChAT). PEDF alone did not increase ChAT, indicating that the observed effect is neurop rotective, not merely an upregulation of motor neuron ChAT. Further, PEDF p reserved motor neuron number, proving a survival effect. We hypothesize tha t PEDF may play important roles in the survival and maintenance of spinal m otor neurons in their neuroprotection against acquired insults in postnatal life. It should be developed further as a therapeutic strategy for motor n euron diseases such as amyotrophic lateral sclerosis (ALS).