Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, Robert Aitken Institute of Clinical Research, University of Birmingham, Birmingham, B15 2TT, UK.
King Edward VI Camp Hill School for Boys, Vicarage Road, Kings Heath, Birmingham, B14 7QJ, UK.
Mol Neurobiol. 2019 Nov;56(11):7490-7507. doi: 10.1007/s12035-019-1614-2. Epub 2019 May 2.
Although neurons in the adult mammalian CNS are inherently incapable of regeneration after injury, we previously showed that exogenous delivery of pigment epithelium-derived factor (PEDF), a 50-kDa neurotrophic factor (NTF), promoted adult retinal ganglion cell neuroprotection and axon regeneration. Here, we show that PEDF and other elements of the PEDF pathway are highly upregulated in dorsal root ganglion neurons (DRGN) from regenerating dorsal column (DC) injury paradigms when compared with non-regenerating DC injury models. Exogenous PEDF was neuroprotective to adult DRGN and disinhibited neurite outgrowth, whilst overexpression of PEDF after DC injury in vivo promoted significant DC axon regeneration with enhanced electrophysiological, sensory, and locomotor function. Our findings reveal that PEDF is a novel NTF for adult DRGN and may represent a therapeutically useful factor to promote functional recovery after spinal cord injury.
虽然成年哺乳动物中枢神经系统中的神经元在受伤后本身无法再生，但我们之前曾表明，外源性给予色素上皮衍生因子（PEDF），一种 50kDa 的神经营养因子（NTF），可促进成年视网膜神经节细胞的神经保护和轴突再生。在这里，我们表明与非再生背柱（DC）损伤模型相比，PEDF 和 PEDF 途径的其他成分在再生背柱损伤范例的背根神经节神经元（DRGN）中高度上调。外源性 PEDF 对成年 DRGN 具有神经保护作用，并抑制神经突生长，而体内 DC 损伤后过表达 PEDF 可促进显著的 DC 轴突再生，并增强电生理、感觉和运动功能。我们的发现表明 PEDF 是成年 DRGN 的一种新型 NTF，可能代表一种有治疗用途的因子，可促进脊髓损伤后的功能恢复。
