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.

Noise-induced hearing loss: Neuropathic pain via Ntrk1 signaling

“…3A) is consistent with the upsurge of Ntrk1 mRNA at this time suggesting that Ntrk1 and/or NGF protein expression could increase further with an extended recovery period. Interestingly, increased NGF expression is associated with increased numbers of trigeminal sensory neurons raising the possibility that NGF/Ntrk1 signaling contributes to the invasion of trigeminal neurons into the CN (Krol et al, 2001; Shore et al, 2000; Zhou et al, 2007). …”

Nerve growth factor‐mediated collateral sprouting of central sensory axons into deafferentated regions of the dorsal horn is enhanced in the absence of the p75 neurotrophin receptor

“…Following rhizotomy in the NGF transgenic mice, levels of NGF are elevated in the crushed dorsal root due to astrogliosis and, in accordance with the neurotrophic hypothesis, these NGF-sensitive axons would respond to the NGF gradient by sprouting into the dorsal root. Previous studies of our NGF transgenic mice have produced numerous examples of NGF-induced collateral sprouting of peripheral nociceptive axons and postganglionic sympathetic axons into CNS structures (Hannila and Kawaja, 1999;Krol et al, 2001;Walsh et al, 1999). At the electron microscope level, small-diameter, unmyelinated axons are seen on the surface of the dorsal root and within the DREZ in NGF/ p75 ϩ/ϩ and NGF/p75 -/-mice.…”

Glial cell line‐derived neurotrophic factor (GDNF) from adult rat tooth serves a distinct population of large‐sized trigeminal neurons

“…There is a substantial body of evidence that proper maintenance and function of trigeminal sensory nerves in the tooth are dependent on target‐derived NGF (Byers et al ., 1992; Naftel et al ., 1994; Wheeler et al ., 1998; Nosrat et al ., 2001). During tooth development, NGF is expressed in the dental papilla and promotes outgrowth of neurites in vitro and regulates survival of developing trigeminal neurons (Mitsiadis et al ., 1992; Qian & Naftel, 1996; Luukko, 1997a,b; Nosrat et al ., 1997a, 2001, 2002; Lillesaar et al ., 1999; Krol et al ., 2001). In adult rat, NGF transcripts and p75 NTR are expressed in the coronal pulp of molar teeth (Byers et al ., 1990, 1992), and trigeminal dental neurons transport target‐derived NGF (Qian & Naftel, 1996; Wheeler et al ., 1998).…”