Comparison of target innervation by sympathetic axons in adult wild type and heterozygous mice for nerve growth factor or its receptor trkA.
Nerve growth factor (NGF), a neurotrophin required for the survival and maintenance of postganglionic sympathetic neurons, mediates its trophic effects by activation of its high-affinity receptor trkA. Null mutant mice lacking either NGF or trkA have profound sympathetic deficits, thus revealing the vital importance of NGF synthesis in target tissues and trkA expression by sympathetic neurons. In this study, we sought to assess whether sympathetic neurons of the superior cervical ganglion (SCG) display alterations in their neurochemical phenotype in adult mice carrying one mutated allele for either NGF or trkA, and whether such differences result in altered patterns of innervation to the submandibular salivary gland and pineal gland. In comparison with adult siblings, levels of trkA protein in the SCG were reduced in age-matched NGF(+/-) and trkA(+/-) mice. While NGF(+/-) mice also had significantly fewer sympathetic axons innervating both the submandibular salivary gland and pineal gland, densities of sympathetic axons in both tissues reached normal levels in trkA(+/-) mice. These findings reveal that while levels of trkA are reduced in SCG neurons of adult NGF(+/-) and trkA(+/-) mice (compared with their wild type counterparts), sympathetic axons are capable of achieving normal patterns of target innervation in trkA(+/-) mice but not in NGF(+/-) mice. As NGF protein levels are not depleted in the submandibular salivary gland and pineal gland of NGF(+/-) mice, a loss of sympathetic neurons [Nat Neurosci 1999; 2:699-705], in combination with reduced levels of trkA protein, may account for perturbed patterns of sympathetic innervation to peripheral tissues.
Ghasemlou
Nader
N
Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
Krol
Karmen M
KM
Macdonald
Devon R
DR
Kawaja
Michael D
MD
D000320:Adrenergic Fibers / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000235:genetics*; D009475:Neurons, Afferent / Q000378:metabolism; D010870:Pineal Gland / Q000294:innervation*; D012333:RNA, Messenger / Q000032:analysis; D020917:Receptor, trkA / Q000235:genetics*; D013363:Submandibular Gland / Q000294:innervation*; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000378:metabolism
D012333:RNA, Messenger; D020932:Nerve Growth Factor; D020917:Receptor, trkA