Expression of beta-preprotachykinin mRNA and tachykinins in rat dorsal root ganglion cells following peripheral or central axotomy.
The changes in gene expression and protein synthesis induced in neurons by axotomy usually lead to increased production of axon constituents and decreased production of molecules related to neurotransmission. Exceptions to this generalization occur, however, and it is unclear whether the injury itself changes the pattern of synthesis or whether individual mechanisms regulate the synthesis of the various axonal components. We used in situ hybridization histochemistry and immunocytochemistry to compare the changes in L4 and L5 rat dorsal root ganglion neuron levels of preprotachykinin mRNA and tachykinin peptides caused by sciatic nerve injury with those caused by dorsal root injury. Both lesions elicit regeneration, although only the axotomized peripheral processes re-establish functional contact with their targets. In the contralateral, intact dorsal root ganglia approximately 17% of neurons contained detectable levels of both mRNAs and peptides. Sciatic nerve section decreased by 70% the number of neurons labeled for preprotachykinin mRNA at three days post-operatively. Not all cells in the ganglion are axotomized by the sciatic nerve lesion; grain counts over the cells spared by the lesion showed an increased level of labeling, possibly a result of collateral sprouting by these spared cells. By two weeks, the number of cells labeled for preprotachykinin mRNA had decreased to 80% of control levels. The numbers of neurons labeled for tachykinin peptides decreased more slowly and reached approximately 50% of control numbers at two weeks. By six months post-operatively, when regeneration is largely complete, the number of neurons containing both mRNAs and peptides returned to normal. In contrast, dorsal root section did not elicit a decrease in the number of neurons labeled either for the mRNAs or the peptides at any of the post-operative intervals examined. These results indicate that axotomy is not the stimulus that elicits changes in the expression of genes coding for tachykinins. Evidence is considered indicating that interruption of the supply of peripherally derived nerve growth factor may be responsible for the changes in gene expression for tachykinins after axotomy.
Henken
D B
DB
Department of Anatomy, Medical College of Pennsylvania, Philadelphia 19129.
Battisti
W P
WP
Chesselet
M F
MF
Murray
M
M
Tessler
A
A
D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression; D009474:Neurons / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000502:physiology*; D015320:Tachykinins / Q000235:genetics*; D013997:Time Factors
D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin