p75 and TrkA neurotrophin receptors in human skin after spinal cord and peripheral nerve injury, with special reference to sensory corpuscles

Abstract

Human skin, including nerves and sensory corpuscles, displays immunoreactivity (IR) for low-(p75) and high-affinity (TrkA-like) receptors for nerve growth factor (NGF), the best characterized member of the family of neurotrophins. This study was designed to analyze the changes induced by spinal cord and peripheral nerve injuries in the expression of neurotrophin receptors in digital skin, with special reference to nerves and sensory corpuscles.Skin biopsy samples were obtained from 1) the hand and toes of normal subjects, 2) below the level of the lesion of patients with spinal cord injury affecting dorsal and lateral funiculi, 3) the cutaneous territory of entrapped peripheral nerves (median and ulnar nerves), and 4) the cutaneous territory of sectioned and grafted nerves (median nerve). The pieces were formalinfixed and paraffin-embedded, cut in serial sections, and processed for immunohistochemistry using antibodies against human p75 and TrkA proteins. The percentage of sensory corpuscles displaying IR for p75 and TrkA-like, as well as the intensity of IR developed within them, was assessed using quantitative image analysis.Spinal cord severance causes a decrease in p75 IR in Meissner and Pacinian corpuscles, whereas TrkA-like IR did not vary. In other nonnervous tissues (i.e., epidermis, sweat glands), both p75 and TrkA-like IR was diminished or even absent. Similar but more severe changes were encountered in the skin from the territory of entrapped nerves. Finally, in subjects with sectioned-grafted nerves, p75 IR was found close to controls in nerves, reduced in Meissner corpuscles, and absent in the inner core of the Pacinian ones; TrkA-like IR was in the perineurium, a small percentage of Meissner corpuscles (about 7%), and the outer core and capsule of the Pacinan corpuscles. In the nonnervous tissues, p75 IR was practically absent, whereas TrkA-like IR did not change. No changes in the expression of neurotrophin receptors were observed in Merkel cells of the different groups.Present results show the following: 1) expression of nerve p75 IR in human cutaneous sensory corpuscles is sensitive to central deafferentation, to blockade or difficulty in axonal transport, and to disruption of axonal

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

“…An adequate innervation seems to be necessary for the expression of p75NTR in keratinocytes, suggesting a role for nerve-derived NGF in the maintenance of epidermal integrity and wound healing (489).…”

Hypo-Osmolar Stress Induces p75NTR Expression by Activating Sp1-Dependent Transcription

“…p75NTR is highly expressed during development, but in most adult tissues, p75NTR is present at low levels (Roux and Barker, 2002). However, injury-induced p75NTR expression has been observed in many CNS pathologies, including traumatic brain injury, seizure, ischemia, and kainate-induced excitotoxity (Kokaia et al, 1998;Lopez et al, 1998;King et al, 2000;Andsberg et al, 2001;Casha et al, 2001;Copray et al, 2003). There is a tight correlation between induced p75NTR expression and subsequent apoptosis of central neurons (Roux et al, 1999), suggesting that regulation of injury-induced p75NTR expression is important for determining the degree of cell loss after injury.…”

Pacinian corpuscle development involves multiple Trk signaling pathways

“…However, the functional importance of TrkB receptors is unclear because mutation in the trkB gene does not alter either the immunohistochemical or the ultrastructural characteristics of Pacinian corpuscles in mice (Gonzalez-Martinez et al, 2004). Expression of TrkA receptors, which can bind NGF as well as NT3, has been observed in the Pacinian corpuscles of humans but not corpuscles of rats or cats (Ribeiro-da-Silva et al, 1991;Vega et al, 1994;Lopez et al, 1998). In contrast, expression of TrkC, the principal Trk receptor for NT3, could not be detected by immunocytochemistry in rat or cat Pacinian corpuscles (Stark et al, 2001).…”

“…In contrast, expression of TrkC, the principal Trk receptor for NT3, could not be detected by immunocytochemistry in rat or cat Pacinian corpuscles (Stark et al, 2001). The inner and outer core cells of Pacinian corpuscles in mice and several other mammalian species also express p75 NTR , a low affinity nonkinase receptor that can modify neurotrophin signal transduction by Trk receptors (Lopez et al, 1998;Albuerne et al, 2000;Stark et al, 2001). Importantly, these studies did not address whether the afferent axons that innervate Pacinian corpuscles expresses any of the three Trk receptors, or p75 NTR ; thus, the potential role of Trk signaling in the development of sensory neurons innervating the corpuscles has not been fully explored.…”

“…Wild-type murine Pacinian corpuscles expressed TrkA, TrkB, and TrkC not only in layers of their capsule (Ribeiro-da-Silva et al, 1991;Vega et al, 1996;Lopez et al, 1998;Stark et al, 2001) but also, and more importantly, in the central afferent axon located in their core. All afferents subserving Pacinian corpuscles coexpressed TrkA and TrkB, and some afferents coexpressed all three Trk receptors.…”