Injured primary sensory neurons switch phenotype for brain-derived neurotrophic factor in the rat

• Published in: Neuroscience Vol. 92; no. 3; pp. 841 - 853
• Main Authors: Zhou, X.-F., Chie, E.T., Deng, Y.-S., Zhong, J.-H., Xue, Qing, Rush, R.A., Xian, C.J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.06.1999; Elsevier
• Subjects: Animals; BDNF; Biological and medical sciences; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Cell Count; Cell Size; Female; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - metabolism; Ganglia, Spinal - pathology; in situ hybridization; Male; Neurons, Afferent - metabolism; Neurons, Afferent - pathology; Neurons, Afferent - physiology; Phenotype; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; RT–PCR; Sciatic Nerve - injuries; Sciatic Nerve - pathology; Sciatic Nerve - physiology; sensory neurons; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; spinal cord; Spinal Cord - metabolism; Vertebrates: nervous system and sense organs; Wounds and Injuries - genetics; Wounds and Injuries - metabolism; BDNF; SP, substance P; NGF, nerve growth factor; RT, reverse transcription; SSC, standard saline citrate; sensory neurons; RT–PCR; NT-3, neurotrophin-3; IR, immunoreactive; BDNF, brain-derived neurotrophic factor; DRG, dorsal root ganglion; PCR, polymerase chain reaction; spinal cord; in situ hybridization; CGRP, calcitonin gene-related peptide; CTB, cholera toxin B; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Spinal cord; Rat; Rodentia; Central nervous system; Peripheral neuropathy; Neurotrophic factor; Vertebrata; Mammalia; Plasticity; Sensory neuron; Spinal ganglion; Brain derived neurotrophic factor; Lesion; Sciatic nerve
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(99)00027-5

Peripheral nerve injury results in plastic changes in the dorsal root ganglia and spinal cord, and is often complicated with neuropathic pain. The mechanisms underlying these changes are not known. We have now investigated the expression of brain-derived neurotrophic factor in the dorsal root ganglia with histochemical and biochemical methods following sciatic nerve lesion in the rat. The percentage of neurons immunoreactive for brain-derived neurotrophic factor in the ipsilateral dorsal root ganglia was significantly increased as early as 24 h after the nerve lesion and the increase lasted for at least two weeks. The level of brain-derived neurotrophic factor messenger RNA was also significantly increased in the ipsi- but not contralateral dorsal root ganglia. Both neurons and satellite cells in the lesioned dorsal root ganglia synthesized brain-derived neurotrophic factor messenger RNA after the nerve lesion. There was a dramatic shift in size distribution of positvie neurons towards large sizes seven days after sciatic nerve lesion. Morphometric analysis and retrograde tracing studies showed that no injured neurons smaller than 600 μm 2 were immunoreactive for brain-derived neurotrophic factor, whereas the majority of large injured neurons were immunoreactive in the ipsilateral dorsal root ganglia seven days postlesion. The brain-derived neurotrophic factor-immunoreactive nerve terminals in the ipsilateral spinal cord were reduced in the central region of lamina II, but increased in more medial regions or deeper into laminae III/IV. These studies indicate that sciatic nerve injury results in a differential regulation of brain-derived neurotrophic factor in different subpopulations of sensory neurons in the dorsal root ganglia. Small neurons switched off their normal synthesis of brain-derived neurotrophic factor, whereas larger ones switched to a brain-derived neurotrophic factor phenotype. The phenotypic switch may have functional implications in neuronal plasticity and generation of neuropathic pain after nerve injury.