title: TrkA-expressing trigeminal sensory neurons display both neurochemical and structural plasticity despite a loss of p75NTR function: responses to normal and elevated levels of nerve growth factor.
abstract: In neural crest-derived sensory ganglia, approximately half of the neuronal population expresses the transmembrane trkA receptor that is required for neuronal binding of target-derived nerve growth factor (NGF). These same neurons also express the p75 neurotrophin receptor (NTR) that increases the affinity of trkA for NGF. Depleting p75NTR expression reduces both the survival of trkA-positive sensory neurons and their afferent innervation of peripheral targets. In this investigation, we assessed the neurochemical and structural plasticity of trigeminal sensory neurons in p75NTR-deficient mice in response to either normal or elevated levels of NGF during postnatal development and into adulthood. Although p75NTR-deficient mice have 30% fewer trigeminal neurons, levels of trkA mRNA expression are modestly elevated in these mutant mice as compared to control mice. The density of central afferent axons and local levels of NGF are, however, comparable between mutant and control animals. Thus, despite the survival of fewer trigeminal neurons, neither ganglionic levels of trkA mRNA expression nor the density of central afferent projections are depleted in p75NTR-deficient mice. In response to elevated levels of NGF protein, transgenic mice with and without p75NTR expression display both increased levels of trkA mRNA expression and a greater density of trigeminal central afferent axons as compared to control mice. These data further reveal that an absence of p75NTR function in trigeminal sensory neurons does not diminish their capacity for NGF-dependent plasticity, namely trkA mRNA expression and collateral growth of central afferent axons.
authors.affiliation: Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: K M
authors.initials: KM
authors.lastname: Krol
authors.forename: E J
authors.initials: EJ
authors.lastname: Stein
authors.forename: J
authors.initials: J
authors.lastname: Elliott
authors.forename: M D
authors.initials: MD
authors.lastname: Kawaja
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D006824:Hybridization, Genetic; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout / Q000235:genetics; D008822:Mice, Transgenic / Q000235:genetics; D020932:Nerve Growth Factor / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency* / Q000235:genetics; D013373:Substance P / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000166:cytology / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D013373:Substance P; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D015740:Calcitonin Gene-Related Peptide