Effect of peripheral nerve injury on dorsal root ganglion neurons in the C57BL/6J mouse: Marked changes both in cell numbers and neuropeptide expression

Several types of changes have been reported to occur in dorsal root ganglia following peripheral nei-ve injury, including loss of neurons and increase s and decreases in peptide expression. However, with regard to loss of neur ons, results have not been consistent, presumably due to different quantita tive methodologies employed and species analyzed. So far, most studies have been conducted on rats; however, with the fast development of the transgen ic techniques, the mouse has become a standard model animal in primary sens ory research. Therefore we used stereological methods to determine the numb er of neurons, as well as the expression of galanin message-associated pept ide, a marker for galanin-expressing neurons, neuropeptide Y, and calcitoni n gene-related peptide in lumbar 5 dorsal root ganglia of both control C57 BL/6J mice and in mice subjected to a 'mid-thigh' sciatic nerve transection (axotomy). In control animals the total number of lumbar 5 dorsal root ganglion neuron s was about 12000. Seven days after axotomy, 24% of the dorsal root ganglio n neurons were lost (P < 0.001), and 54% were lost 28 days after axotomy (P < 0.001). With regard to the percentage of peptide-expressing neurons, the results obtained showed that both galanin message-associated peptide (from < 1% to about 21%) and neuropeptide Y (from < 1% to about 16%) are upregul ated, whereas calcitonin gene-related peptide is downregulated (from about 41% to about 14%) following axotomy. Results obtained with retrograde label ing of the axotomized dorsal root ganglion neurons indicate that the neurop eptide regulations may be even more pronounced, if the analysis is confined to the axotomized dorsal root ganglion neurons rather than including the e ntire neuron population. We also applied conventional profile-based countin g methods to compare with the stereological data and, although the results were comparable considering the trends of changes following axotomy, the ac tual percentage obtained with the two methods differed markedly, both for n europeptide Y- and, especially, for galanin message-associated peptide-posi tive neurons. These present results demonstrate that marked species differences exist wit h regard to the effect of nerve injury on dorsal root ganglion neurons. Thu s, whereas no neuron loss is seen in rat up to 4 weeks after a 'mid-thigh' transection [Tandrup et al. (2000) J. Comp. Neurol. 422, 172-180], the pres ent results indicate a dramatic loss already after 1 week in mouse. It is s uggested that the proximity in physical distance of the lesion to the cell body is a critical factor for the survival of the target-deprived neurons. Finally, stereological methodology seems warranted when assessing the total number of neurons as well as changes in peptide regulations after axotomy in mouse. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights rese rved.