Increased levels of trkB mRNA and trkB protein-like immunoreactivity in the injured rat and cat spinal cord.

Frisén, Jonas; Verge, Valerie M. K.; Cullheim, Staffan; Persson, Håkan; Fried, Kaj; Middlemas, David S.; Hunter, Tony; Hökfelt, Tomas; Risling, Mårten

doi:10.1073/pnas.89.23.11282

Cited by 121 publications

(77 citation statements)

References 40 publications

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“…Conversely, the expression of TrkA in peripheral nerves and sensory corpuscles is conflicting, although we observed TrkA-like IR as a regular feature of perineurial and corpuscular perineurial-related cells as well as corpuscular Schwannrelated cells. Neither TrkA mRNA nor TrkA was detected in Schwann cells (Funakoshi et al, 1993;Yamamoto et al, 1993;Anton et al, 1994;Liu et al, 1995;Offenhausser et al, 1995), but it was localized in meningeal and nonnervous cells sheathing the ventral root of rat spinal nerves (Risling et al, 1994) and in leptomeningeal cells (Frisen et al, 1992) which share the origin with perineurial cells (Halata et al, 1990). On the other hand, observations in Merkel cells regarding p75 are in good agreement with previous reports (Ribeiro da Silva et al, 1991;Narisawa et al, 1992;Vega et al, 1992;English et al, 1994).…”

Section: Nerves and Sensory Corpusclessupporting

confidence: 82%

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

et al. 1998

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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

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Section: Nerves and Sensory Corpusclessupporting

confidence: 82%

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

et al. 1998

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“…Thus, the injury-related effects on the survival of neurons in the retina may be due to the intraocular synthesis and release of molecules that are specific trophins for RGCs. By analogy with injury-induced responses in other parts of the CNS, RGC survival can also be influenced by changes in the expression of specific receptors (29) or by the synthesis and release of other trophic molecules known to be present in the eye such as acidic or basic fibroblast growth factors (30) and ciliary neurotrophic factor (31). Our finding that anterior ocular injections had a more prolonged survival effect than posterior injections suggests that the critical molecules may be released from endogenous sources in a protracted fashion.…”

Section: Resultsmentioning

confidence: 99%

Effects of ocular injury and administration ofbrain-derived neurotrophic factor on survival and regrowth of axotomized retinalganglion cells.

Mansour-Robaey

Clarke

Wang

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

651

445

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Optic nerve tansection in adult rats results in the death of -50% of the axotomized retinal on cells (RGCs) by 1 week and nearly 90% by 2 weeks after injury. RGC Lang. ROCs were retrogradely labeled with Fluorogold (Fluorochrome, Englewood, CO; 2% in 0.9% NaCl containing 10%o dimethyl sulfoxide) applied to the surface of both SC, as described for 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (diI) (11,12). For the experiments in which a correlation between RGC survival and axonal regrowth was investigated (as described below), horseradish peroxidase (HRP; Boehringer Mannheim) was applied to the distal tip of the PN graft, "1 cm from the eye, 6 weeks after the graft was attached to the ocular stump ofthe ON (13).ON Transection. One week after Fluorogold application, the left ON was transected 0.5 mm from the eye (1). In some animals, a segment of autologous sciatic nerve was attached to the ocular stump of the transected ON to test the capacity of the RGCs to regenerate and extend their axons (13).Injection Procedure. Anesthetized animals received single injections 3 or 6 days before or 0-10 days after ON transection. Multiple injections were given on postoperative days 0, 3, 7, and 10 for the animals without PN grafts and on days 0, 3, and 7 for the animals with PN grafts. Intraocular injections were made with a 10-A4 Hamilton syringe fitted with a 26-gauge needle whose tip was inserted into the vitreous space by an anterior or posterior approach. For the anterior approach, a drop of 2% lidocaine (Xylocaine) was applied to the conjunctiva, and the needle was inserted through the cornea-sclerajunction and advanced into the vitreous chamber, avoiding direct contact with the retina. By this approach, the needle usually pierced the margins of the iris and could damage the surface of the lens. After injection, Polysporin ointment was applied to the puncture site. For the posterior approach, the needle was inserted through the sclera and retina at the time of ON transection; this route avoided direct injury to the iris or lens. All experiments to determine the range of effective times for BDNF and control injections, as

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“…Indeed, there is abundant evidence supporting the concept that neurotrophins and their receptors have a protective effect on many neuronal populations after injury (Sendtner et al, 1992;Yan et al, 1992Yan et al, , 1993Koliatsos et al, 1993;Arenas and Persson, 1994;Li et al, 1994). For instance, it has been shown that axotomy results in changes in the expression of neurotrophins and p75 and Trk receptors in neurons, glial cells, and target tissues (Heumann et al, 1987;Ernfors et al, 1989;Frisén et al, 1992Frisén et al, , 1993Meyer et al, 1992;Beck et al, 1993;Funakoshi et al, 1993;Koliatsos et al, 1993;Mearow et al, 1993;Merlio et al, 1993;Piehl et al, 1994;Kobayashi et al, 1996). Furthermore, exogenously administered neurotrophins can rescue neurons from injury-induced cell death in axotomy paradigms (Sendtner et al, 1992;Yan et al, 1992;Koliatsos et al, 1993Koliatsos et al, , 1994Yan et al, 1993;Arenas and Persson, 1994).…”

Section: Abstract: Trkb; Cns; Cell Death; Axotomy; Hippocampus; Motomentioning

confidence: 99%

TrkB Signaling Is Required for Postnatal Survival of CNS Neurons and Protects Hippocampal and Motor Neurons from Axotomy-Induced Cell Death

et al. 1997

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Newborn mice carrying targeted mutations in genes encoding neurotrophins or their signaling Trk receptors display severe neuronal deficits in the peripheral nervous system but not in the CNS. In this study, we show that trkB (Ϫ/Ϫ) mice have a significant increase in apoptotic cell death in different regions of the brain during early postnatal life. The most affected region in the brain is the dentate gyrus of the hippocampus, although elevated levels of pyknotic nuclei were also detected in cortical layers II and III and V and VI, the striatum, and the thalamus. Furthermore, axotomized hippocampal and motor neurons of trkB (Ϫ/Ϫ) mice have significantly lower survival rates than those of wild-type littermates. These results suggest that neurotrophin signaling through TrkB receptors plays a role in the survival of CNS neurons during postnatal development. Moreover, they indicate that TrkB receptor signaling protects subpopulations of CNS neurons from injury-and axotomy-induced cell death. Key words: TrkB; CNS; cell death; axotomy; hippocampus; motor neuronNeurotrophins, including nerve growth factor (NGF), brainderived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5, and NT-6, have been shown to promote neuronal survival of a variety of neuronal populations (Fariñas and Reichardt, 1996). Mutant mice lacking the genes encoding each of these neurotrophins or their receptors have illustrated the exquisite requirement of neurotrophin signaling for the survival of distinct neuronal populations in the peripheral nervous system during embryonic development (Snider, 1994;Barbacid, 1995;Fariñas and Reichardt, 1996). However, very few defects have been detected in the CNS of these mutant mice.It has been suggested (Snider, 1994;Fariñas and Reichardt, 1996) that the absence of CNS defects in these animals might be attributable to the significant overlap in the pattern of TrkB and TrkC receptors in CNS neurons Merlio et al., 1992). However, this hypothesis seems unlikely, because double mutant mice lacking both of these Trk receptors do not show any obvious defects in the CNS, at least during embryonic development (Silos-Santiago et al., 1997). These observations suggest that the growth factor requirements of CNS neurons are more complex than those of the periphery. Another possibility is that CNS neurons require only neurotrophin support during postnatal development or even in adult animals. Alternatively, the role of neurotrophins in the CNS might involve aspects of neuronal function other than survival. Indeed, neurotrophin signaling has been implicated in physiological events such as synthesis of neuroactive substances (Lindsay and Harmar, 1989;Ip et al., 1993;Nawa et al., 1993Nawa et al., , 1994Jones et al., 1994;Marty et al., 1996), synaptic efficacy and rearrangement (Lohof et al., 1993;Cabelli et al., 1995;Kang and Schuman, 1995;Korte et al., 1995;Lesser and Lo, 1995;Levine et al., 1995;Lo, 1995;Thoenen, 1995;Patterson et al., 1996) and modulation of dendritic and axonal growth (Diamond et al., 1992;Schnell ...

show abstract

Increased levels of trkB mRNA and trkB protein-like immunoreactivity in the injured rat and cat spinal cord.

Abstract: Expression of neurotrophins and neurotroph-

Cited by 121 publications

References 40 publications

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

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

Effects of ocular injury and administration ofbrain-derived neurotrophic factor on survival and regrowth of axotomized retinalganglion cells.

TrkB Signaling Is Required for Postnatal Survival of CNS Neurons and Protects Hippocampal and Motor Neurons from Axotomy-Induced Cell Death

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