Bennett D L, Michael G J, Ramachandran N, Munson J B, Averill S, Yan Q, McMahon S B, Priestley J V
Department of Physiology, United Medical and Dental Schools (St. Thomas' Campus), London, SE1 7EH, United Kingdom.
J Neurosci. 1998 Apr 15;18(8):3059-72. doi: 10.1523/JNEUROSCI.18-08-03059.1998.
Several lines of evidence suggest that neurotrophin administration may be of some therapeutic benefit in the treatment of peripheral neuropathy. However, a third of sensory neurons do not express receptors for the neurotrophins. These neurons are of small diameter and can be identified by the binding of the lectin IB4 and the expression of the enzyme thiamine monophosphatase (TMP). Here we show that these neurons express the receptor components for glial-derived neurotrophic factor (GDNF) signaling (RET, GFRalpha-1, and GFRalpha-2). In lumbar dorsal root ganglia, virtually all IB4-labeled cells express RET mRNA, and the majority of these cells (79%) also express GFRalpha-1, GFRalpha-2, or GFRalpha-1 plus GFRalpha-2. GDNF, but not nerve growth factor (NGF), can prevent several axotomy-induced changes in these neurons, including the downregulation of IB4 binding, TMP activity, and somatostatin expression. GDNF also prevents the slowing of conduction velocity that normally occurs after axotomy in a population of small diameter DRG cells and the A-fiber sprouting into lamina II of the dorsal horn. GDNF therefore may be useful in the treatment of peripheral neuropathies and may protect peripheral neurons that are refractory to neurotrophin treatment.
多项证据表明，给予神经营养因子可能对治疗周围神经病变具有一定的治疗益处。然而，三分之一的感觉神经元不表达神经营养因子的受体。这些神经元直径较小，可通过凝集素IB4的结合以及硫胺单磷酸酶（TMP）的表达来识别。在此我们表明，这些神经元表达胶质细胞源性神经营养因子（GDNF）信号传导的受体成分（RET、GFRalpha-1和GFRalpha-2）。在腰段背根神经节中，几乎所有IB4标记的细胞都表达RET mRNA，并且这些细胞中的大多数（79%）也表达GFRalpha-1、GFRalpha-2或GFRalpha-1加GFRalpha-2。GDNF而非神经生长因子（NGF）能够预防这些神经元中几种轴突切断诱导的变化，包括IB4结合、TMP活性和生长抑素表达的下调。GDNF还能预防小直径背根神经节（DRG）细胞群体中轴突切断后通常出现的传导速度减慢以及A纤维向背角II层的芽生。因此，GDNF可能有助于治疗周围神经病变，并可能保护对神经营养因子治疗难治的周围神经元。
