Neurotrophins Act as Neuroendocrine Regulators of Skin Homeostasis in Health and Disease

E. M. J. Peters; U. Raap; P. Welker; A. Tanaka; H. Matsuda; S. Pavlovic-Masnicosa; S. Hendrix; C. Pincelli

doi:10.1055/s-2007-961812

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2007; 39(2): 110-124
DOI: 10.1055/s-2007-961812

Review

Neurotrophins Act as Neuroendocrine Regulators of Skin Homeostasis in Health and Disease

E. M. J. Peters¹ , U. Raap² , P. Welker³ , A. Tanaka⁴ , H. Matsuda⁴ , S. Pavlovic-Masnicosa¹ , S. Hendrix⁵ , C. Pincelli⁶

¹Cutaneous Psychoneuroimmunology, Internal Medicine - Psychosomatics, Charité - Universitätsmedizin Berlin, Berlin, Germany
²Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany
³Center of Anatomy, Department of Vegetative Anatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany
⁴Laboratory of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Graduate School, Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology, Tokyo, Japan
⁵Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany
⁶Institute of Dermatology, University of Modena and Reggio Emilia, Modena, Italy

Abstract

Neurotrophins regulate cutaneous innervation, act as growth and motility factors on structural skin cells such as keratinocytes and fibroblasts, modulate cutaneous immune function and even serve as stress mediators in skin biology. The multilayered neurotrophin interaction with skin biology through high affinity specific tyrosinekinase receptors and the Janus-faced p75 receptor, which depending on ligand and co-receptor expression can serve as a low-affinity pan-neurotrophin receptor or a high affinity proneurotrophin receptor, guaranties this neuroendocrine peptide family a central position in the control of skin homeostasis in health and disease. It is a challenging task for future research efforts to integrate our knowledge on differential neurotrophin expression patterns and signaling pathways into complex concepts of neuroendocrine tissue remodeling and pathogenetic processes. In addition, we need to improve our understanding of the role of neurotrophin processing enzymes, associated co-receptors and intracellular adaptor molecules in specific cutaneous cell populations to design precise interaction tools for research and treatment. Such tools will allow us to utilize this ancient growth factor family in the management of neurotrophin responsive pathogenetic pathways and cutaneous diseases such as neurogenic inflammation, peripheral nerve degeneration, wound healing, atopic dermatitis or psoriasis.

Keywords

nerve growth factor - brain derived neurotrophic factor - p75 neurotrophin receptor - tyrosinekinase receptor - skin - skin appendages - cutaneous inflammation

Full Text

References

1 Kane MO, Murphy EP, Kirby B. The role of corticotropin-releasing hormone in immune-mediated cutaneous inflammatory disease. Exp Dermatol. 2006; 15 143-153
2 Ito N, Ito T, Paus R. The human hair follicle has established a fully functional peripheral equivalent of the hypothamalic-pituitary-adrenal-axis (HPA). Exp Dermatol. 2005; 14 158
3 Botchkarev VA, Botchkareva NV, Peters EM, Paus R. Epithelial growth control by neurotrophins: leads and lessons from the hair follicle. Prog Brain Res. 2004; 146 493-513
4 Alleva E, Santucci D. Psychosocial vs. “physical” stress situations in rodents and humans: role of neurotrophins. Physiol Behav. 2001; 73 313-320
5 Vega JA, Garcia-Suarez O, Hannestad J, Perez-Perez M, Germana A. Neurotrophins and the immune system. J Anat. 2003; 203 1-19
6 Kawamoto K, Matsuda H. Nerve growth factor and wound healing. Prog Brain Res. 2004; 146 369-384
7 Anand P. Neurotrophic factors and their receptors in human sensory neuropathies. Prog Brain Res. 2004; 146 477-492
8 Sariola H. The neurotrophic factors in non-neuronal tissues. Cell Mol Life Sci. 2001; 58 1061-1066
9 Botchkarev VA. Neurotrophins and their role in pathogenesis of alopecia areata. J Investig Dermatol Symp Proc. 2003; 8 195-198
10 Raap U, Kapp A. Neuroimmunological findings in allergic skin diseases. Curr Opin Allergy Clin Immunol. 2005; 5 419-424
11 Harrison SM, Davis BM, Nishimura M, Albers KM, Jones ME, Phillips HS. Rescue of NGF-deficient mice I: transgenic expression of NGF in skin rescues mice lacking endogenous NGF. Brain Res Mol Brain Res. 2004; 122 116-125
12 Zouboulis CC. Human skin: an independent peripheral endocrine organ. Horm Res. 2000; 54 230-242
13 Slominski A. Neuroendocrine system of the skin. Dermatology. 2005; 211 199-208
14 Levi-Montalcini R, Cohen S. Effects of the extract of the mouse submaxillary salivary glands on the sympathetic system of mammals. Ann N Y Acad Sci. 1960; 85 324-341
15 Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. Embo J. 1982; 1 549-553
16 Hohn A, Leibrock J, Bailey K, Barde YA. Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature. 1990; 344 339-341
17 Berkemeier LR, Winslow JW, Kaplan DR, Nikolics K, Goeddel DV, Rosenthal A. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron. 1991; 7 857-866
18 Hallbook F, Ibanez CF, Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron. 1991; 6 845-858
19 Lee R, Kermani P, Teng KK, Hempstead BL. Regulation of cell survival by secreted proneurotrophins. Science. 2001; 294 1945-1948
20 Lu B, Pang PT, Woo NH. The yin and yang of neurotrophin action. Nat Rev Neurosci. 2005; 6 603-614
21 Schulze-Osthoff K, Ferrari D, Los M, Wesselborg S, Peter ME. Apoptosis signaling by death receptors. Eur J Biochem. 1998; 254 439-459
22 Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 2001; 104 487-501
23 Johnson D, Lanahan A, Buck CR, Sehgal A, Morgan C, Mercer E, Bothwell M, Chao M. Expression and structure of the human NGF receptor. Cell. 1986; 47 545-554
24 Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci. 2003; 4 299-309
25 Barbacid M. Neurotrophic factors and their receptors. Curr Opin Cell Biol. 1995; 7 148-155
26 Di Marco E, Mathor M, Bondanza S, Cutuli N, Marchisio PC, Cancedda R, De Luca M. Nerve growth factor binds to normal human keratinocytes through high and low affinity receptors and stimulates their growth by a novel autocrine loop. J Biol Chem. 1993; 268 22838-22846
27 Botchkarev VA, Yaar M, Botchkareva NV, Peters EMJ, Marconi A, Raychaudhuri SP, Raychaudhuri SP, Paus R, Pincelli C. Neurotrophins in Skin Biology. J Invest Dermatol. 2006; in press
28 Barker PA. p75NTR is positively promiscuous: novel partners and new insights. Neuron. 2004; 42 529-533
29 Yardley G, Relf B, Lakshmanan J, Reinshagen M, Moore GP. Expression of nerve growth factor mRNA and its translation products in the anagen hair follicle. Exp Dermatol. 2000; 9 283-289
30 Yiangou Y, Facer P, Sinicropi DV, Boucher TJ, Bennett DL, McMahon SB, Anand P. Molecular forms of NGF in human and rat neuropathic tissues: decreased NGF precursor-like immunoreactivity in human diabetic skin. J Peripher Nerv Syst. 2002; 7 190-197
31 Peters EM, Hendrix S, Golz G, Klapp BF, Arck PC, Paus R. Nerve Growth Factor and Its Precursor Differentially Regulate Hair Cycle Progression in Mice. J Histochem Cytochem. 2005; 11 11
32 Peters EM, Stieglitz MG, Liezman C, Overall RW, Nakamura M, Hagen E, Klapp BF, Arck P, Paus R. p75 Neurotrophin Receptor-Mediated Signaling Promotes Human Hair Follicle Regression (Catagen). Am J Pathol. 2006; 168 221-234
33 Ibanez CF. Jekyll-Hyde neurotrophins: the story of proNGF. Trends Neurosci. 2002; 25 284-286
34 Reinshagen M, Geerling I, Lakshmanan J, Rohm H, Lutz MP, Soinila S, Eysselein VE, Adler G. Commercial mouse and human nerve growth factors contain nerve growth factor prohormone isoforms. J Neurosci Meth. 1997; 74 75-81
35 Reinshagen M, Geerling I, Eysselein VE, Adler G, Huff KR, Moore GP, Lakshmanan J. Commercial Recombinant Human β-Nerve Growth Factor and Adult Rat Dorsal Root Ganglia Contain an Identical Molecular Species of Nerve Growth Factor Prohormone. J Neurochem. 2000; 74 2127-2133
36 Dechant G. Molecular interactions between neurotrophin receptors. Cell Tissue Res. 2001; 305 229-238
37 Huang EJ, Reichardt LF. Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem. 2003; 72 609-642
38 Teng KK, Hempstead BL. Neurotrophins and their receptors: signaling trios in complex biological systems. Cell Mol Life Sci. 2004; 61 35-48
39 Arevalo JC, Pereira DB, Yano H, Teng KK, Chao MV. Identification of a switch in neurotrophin signaling by selective tyrosine phosphorylation. J Biol Chem. 2006; 281 1001-1007
40 Stephens RM, Loeb DM, Copeland TD, Pawson T, Greene LA, Kaplan DR. Trk receptors use redundant signal transduction pathways PLC-gamma 1 to mediate NGF responses. Neuron. 1994; 12 691-705
41 Knusel B, Rabin SJ, Hefti F, Kaplan DR. Regulated neurotrophin receptor responsiveness during neuronal migrationand early differentiation. J Neurosci. 1994; 14 1542-1554
42 Hempstead BL, Martin-Zanca D, Kaplan DR, Parada LF, Chao MV. High-affinity NGF binding requires coexpression of the trk and the low-affinity NGF receptor. Nature. 1991; 350 678-683
43 Seidah NG, Benjannet S, Pareek S, Chretien M, Murphy RA. Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases. FEBS Lett. 1996; 379 247-250
44 Seidah NG, Benjannet S, Pareek S, Savaria D, Hamelin J, Goulet B, Laliberte J, Lazure C, Chretien M, Murphy RA. Cellular processing of the nerve growth factor precursor by the mammalian pro-protein convertases. Biochem J. 1996; 314 951-960
45 Rose CR, Blum R, Pichler B, Lepier A, Kafitz KW, Konnerth A. Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling cells. Nature. 2003; 426 74-78
46 Hisaoka M, Sheng WQ, Tanaka A, Hashimoto H. Gene expression of TrkC (NTRK3) in human soft tissue tumours. J Pathol. 2002; 197 661-667
47 Haapasalo A, Koponen E, Hoppe E, Wong G, Castren E. Truncated trkB.T1 is dominant negative inhibitor of survival. Biochem Biophys Res Commun. 2001; 280 1352-1358
48 Howe CL, Mobley WC. Long-distance retrograde neurotrophic signaling. Curr Opin Neurobiol. 2005; 15 40-48
49 Guan W, Puthenveedu MA, Condic ML. Sensory neuron subtypes have unique substratum preference and receptor expression before target innervation. J Neurosci. 2003; 23 1781-1791
50 Hempstead BL. Sculpting organ innervation. J Clin Invest. 2004; 113 811-813
51 Davies AM, Bandtlow C, Heumann R, Korsching S, Rohrer H, Thoenen H. Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. Nature. 1987; 326 353-358
52 Donnerer J. Improved neurochemical recovery of 6-hydroxydopamine-lesioned postganglionic sympathetic neurons by nerve growth factor in the adult rat. Neurosci Lett. 1996; 221 33-36
53 Schicho R, Skofitsch G, Donnerer J. Regenerative effect of human recombinant NGF on capsaicin-lesioned sensory neurons in the adult rat. Brain Res. 1999; 815 60-69
54 Rice FL, Albers KM, Davis BM, Silos-Santiago I, Wilkinson GA, LeMaster AM, Ernfors P, Smeyne RJ, Aldskogius H, Phillips HS, Barbacid M, DeChiara TM, Yancopoulos GD, Dunne CE, Fundin BT. Differential dependency of unmyelinated and A delta epidermal and upper dermal innervation on neurotrophins, trk receptors, and p75LNGFR. Dev Biol. 1998; 198 57-81
55 Otten U, Goedert M, Mayer N, Lembeck F. Requirement of nerve growth factor for development of substance P-containing sensory neurones. Nature. 1980; 287 158-159
56 Stucky CL, Koltzenburg M, Schneider M, Engle MG, Albers KM, Davis BM. Overexpression of nerve growth factor in skin selectively affects the survival and functional properties of nociceptors. J Neurosci. 1999; 19 8509-8516
57 Krimm RF, Davis BM, Albers KM. Cutaneous overexpression of neurotrophin-3 (NT3) selectively restores sensory innervation in NT3 gene knockout mice. J Neurobiol. 2000; 43 40-49
58 Szeder V, Grim M, Kucera J, Sieber-Blum M. Neurotrophin-3 signaling in mammalian Merkel cell development. Dev Dyn. 2003; 228 623-629
59 Sieber-Blum M, Szeder V, Grim M. The role of NT-3 signaling in Merkel cell development. Prog Brain Res. 2004; 146 63-72
60 LeMaster AM, Krimm RF, Davis BM, Noel T, Forbes ME, Johnson JE, Albers KM. Overexpression of brain-derived neurotrophic factor enhances sensory innervation and selectively increases neuron number. J Neurosci. 1999; 19 5919-5931
61 Stucky C, Shin J, Lewin G. Neurotrophin-4. A survival factor for adult sensory neurons. Curr Biol. 2002; 12 1401-1404
62 Fundin BT, Silos-Santiago I, Ernfors P, Fagan AM, Aldskogius H, DeChiara TM, Phillips HS, Barbacid M, Yancopoulos GD, Rice FL. Differential dependency of cutaneous mechanoreceptors on neurotrophins, trk receptors, and P75 LNGFR. Dev Biol. 1997; 190 94-116
63 Botchkarev VA, Botchkareva NV, Lommatzsch M, Peters EM, Lewin GR, Subramaniam A, Braun A, Renz H, Paus R. BDNF overexpression induces differential increases among subsets of sympathetic innervation in murine back skin. Eur J Neurosci. 1998; 10 3276-3283
64 Botchkarev VA, Botchkareva NV, Albers KM, Chen LH, Welker P, Paus R. A role for p75 neurotrophin receptor in the control of apoptosis-driven hair follicle regression. Faseb J. 2000; 14 1931-1942
65 Botchkareva NV, Botchkarev VA, Albers KM, Metz M, Paus R. Distinct roles for nerve growth factor and brain-derived neurotrophic factor in controlling the rate of hair follicle morphogenesis. J Invest Dermatol. 2000; 114 314-320
66 Palkina TN, Sharov AA, Sharov TY, Botchkarev VA. Neurotrophins in autoimmune diseases: possible implications for alopecia areata. J Investig Dermatol Symp Proc. 2005; 10 282
67 Ritter AM, Woodbury CJ, Davis BM, Albers K, Koerber HR. Excess target-derived neurotrophin-3 alters the segmental innervation of the skin. Eur J Neurosci. 2001; 14 411-418
68 Snider WD. Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell. 1994; 77 627-638
69 Peters EM, Handjiski B, Kuhlmei A, Hagen E, Bielas H, Braun A, Klapp BF, Paus R, Arck PC. Neurogenic inflammation in stress-induced termination of murine hair growth is promoted by nerve growth factor. Am J Pathol. 2004; 165 259-271
70 Di Marco E, Marchisio PC, Bondanza S, Franzi AT, Cancedda R, De Luca M. Growth-regulated synthesis and secretion of biologically active nerve growth factor by human keratinocytes. J Biol Chem. 1991; 266 21718-21722
71 Pincelli C, Sevignani C, Manfredini R, Grande A, Fantini F, Bracci-Laudiero L, Aloe L, Ferrari S, Cossarizza A, Giannetti A. Expression and function of nerve growth factor and nerve growth factor receptor on cultured keratinocytes. J Invest Dermatol. 1994; 103 13-18
72 Pincelli C. Nerve growth factor and keratinocytes: a role in psoriasis. Eur J Dermatol. 2000; 10 85-90
73 Pincelli C, Marconi A. Autocrine nerve growth factor in human keratinocytes. J Dermatol Sci. 2000; 22 71-79
74 Marconi A, Terracina M, Fila C, Franchi J, Bonte F, Romagnoli G, Maurelli R, Failla CM, Dumas M, Pincelli C. Expression and function of neurotrophins and their receptors in human keratinocytes. J Invest Dermatol. 2003; 121 1515-1521
75 Paus R, Luftl M, Czarnetzki BM. Nerve growth factor modulates keratinocyte proliferation in murine skin organ culture. Br J Dermatol. 1994; 130 174-180
76 Botchkarev VA, Metz M, Botchkareva NV, Welker P, Lommatzsch M, Renz H, Paus R. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 act as “epitheliotrophins” in murine skin. Lab Invest. 1999; 79 557-572
77 Haake AR, Polakowska RR. Cell death by apoptosis in epidermal biology. J Invest Dermatol. 1993; 101 107-112
78 Pincelli C, Haake AR, Benassi L, Grassilli E, Magnoni C, Ottani D, Polakowska R, Franceschi C, Giannetti A. Autocrine nerve growth factor protects human keratinocytes from apoptosis through its high affinity receptor (TRK): a role for BCL-2. J Invest Dermatol. 1997; 109 757-764
79 Marconi A, Vaschieri C, Zanoli S, Giannetti A, Pincelli C. Nerve growth factor protects human keratinocytes from ultraviolet-B-induced apoptosis. J Invest Dermatol. 1999; 113 920-927
80 Biswas SC, Greene LA. Nerve growth factor (NGF) down-regulates the Bcl-2 homology 3 (BH3) domain-only protein Bim and suppresses its proapoptotic activity by phosphorylation. J Biol Chem. 2002; 277 49511-49516
81 Marconi. et al. . , in press
82 Micera A, Vigneti E, Pickholtz D, Reich R, Pappo O, Bonini S, Maquart FX, Aloe L, Levi-Schaffer F. Nerve growth factor displays stimulatory effects on human skin and lung fibroblasts, demonstrating a direct role for this factor in tissue repair. Proc Natl Acad Sci USA. 2001; 98 6162-6167
83 Micera A, Puxeddu I, Aloe L, Levi-Schaffer F. New insights on the involvement of Nerve Growth Factor in allergic inflammation and fibrosis. Cytokine Growth Factor Rev. 2003; 14 369-374
84 Hasan W, Zhang R, Liu M, Warn JD, Smith PG. Coordinate expression of NGF and alpha-smooth muscle actin mRNA and protein in cutaneous wound tissue of developing and adult rats. Cell Tissue Res. 2000; 300 97-109
85 Blasing H, Hendrix S, Paus R. Pro-inflammatory cytokines upregulate the skin immunoreactivity for NGF, NT-3, NT-4 and their receptor, p75NTR in vivo: a preliminary report. Arch Dermatol Res. 2005; 296 580-584
86 Matsuda H, Koyama H, Sato H, Sawada J, Itakura A, Tanaka A, Matsumoto M, Konno K, Ushio H, Matsuda K. Role of nerve growth factor in cutaneous wound healing: accelerating effects in normal and healing-impaired diabetic mice. J Exp Med. 1998; 187 297-306
87 von Schack D, Casademunt E, Schweigreiter R, Meyer M, Bibel M, Dechant G. Complete ablation of the neurotrophin receptor p75NTR causes defects both in the nervous and the vascular system. Nat Neurosci. 2001; 4 977-978
88 Kraemer R, Hempstead BL. Neurotrophins: novel mediators of angiogenesis. Front Biosci. 2003; 1 s1181-s1186
89 Calza L, Giardino L, Giuliani A, Aloe L, Levi-Montalcini R. Nerve growth factor control of neuronal expression of angiogenetic and vasoactive factors. Proc Natl Acad Sci USA. 2001; 98 4160-4165
90 Raychaudhuri SK, Raychaudhuri SP, Weltman H, Farber EM. Effect of nerve growth factor on endothelial cell biology: proliferation and adherence molecule expression on human dermal microvascular endothelial cells. Arch Dermatol Res. 2001; 293 291-295
91 Gibran NS, Tamura R, Tsou R, Isik FF. Human dermal microvascular endothelial cells produce nerve growth implications for wound repair. Shock. 2003; 19 127-130
92 Emanueli C, Salis MB, Pinna A, Graiani G, Manni L, Madeddu P. Nerve growth factor promotes angiogenesis and arteriogenesis in ischemic hindlimbs. Circulation. 2002; 106 2257-2262
93 Tanaka A, Wakita U, Kambe N, Iwasaki T, Matsuda H. An autocrine function of nerve growth factor for cell cycle regulation of vascular endothelial cells. Biochem Biophys Res Commun. 2004; 313 1009-1014
94 Steinhoff M, Stander S, Seeliger S, Ansel JC, Schmelz M, Luger T. Modern aspects of cutaneous neurogenic inflammation. Arch Dermatol. 2003; 139 1479-1488
95 Peters EMJ, Ericson M, Hosoi J, Seiffert K, Hordinsky M, Ansel JC, Paus R, Scholzen TE. Neuropeptidergic controls in cutaneous biology: Physiological and clinical significance. J Invest Dermatol. 2006; , in press
96 Weller K, Foitzik K, Paus R, Syska W, Maurer M. Mast cells are required for normal healing of skin wounds in mice. Faseb J. 2006; 20 2366-2368
97 Metz M, Piliponsky AM, Chen CC, Lammel V, Abrink M, Pejler G, Tsai M, Galli SJ. Mast cells can enhance resistance to snake and honeybee venoms. Science. 2006; 313 526-530
98 Suzuki R, Furuno T, McKay DM, Wolvers D, Teshima R, Nakanishi M, Bienenstock J. Direct neurite-mast cell communication in vitro occurs via the neuropeptide substance P. J Immunol. 1999; 163 2410-2415
99 Nakamura M, Toyoda M, Morohashi M. Pruritogenic mediators in psoriasis vulgaris: comparative itch-associated cutaneous factors. Br J Dermatol. 2003; 149 718-730
100 Jarvikallio A, Harvima IT, Naukkarinen A. Mast cells, nerves and neuropeptides in atopic dermatitis and eczema. Arch Dermatol Res. 2003; 295 2-7
101 Peters EM, Kuhlmei A, Tobin DJ, Muller-Rover S, Klapp BF, Arck PC. Stress exposure modulates peptidergic innervation and degranulates mast cells in murine skin. Brain Behav Immun. 2005; 19 252-262
102 Ansel JC, Kaynard AH, Armstrong CA, Olerud J, Bunnett N, Payan D. Skin-nervous system interactions. J Invest Dermatol. 1996; 106 198-204
103 Toyoda M, Nakamura M, Makino T, Hino T, Kagoura M, Morohashi M. Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis. Br J Dermatol. 2002; 147 71-79
104 Tanaka A, Matsuda H. Expression of nerve growth factor in itchy skins of atopic NC/NgaTnd mice. J Vet Med Sci. 2005; 67 915-919
105 Leon A, Buriani A, Dal Toso R, Fabris M, Romanello S, Aloe L, Levi-Montalcini R. Mast cells synthesize, store, and release nerve growth factor. Proc Natl Acad Sci USA. 1994; 91 3739-3743
106 Groneberg DA, Serowka F, Peckenschneider N, Artuc M, Grutzkau A, Fischer A, Henz BM, Welker P. Gene expression and regulation of nerve growth factor in atopic dermatitis mast cells and the human mast cell line-1. J Neuroimmunol. 2005; 161 87-92
107 Nilsson G, Forsberg-Nilsson K, Xiang Z, Hallbook F, Nilsson K, Metcalfe DD. Human mast cells express functional TrkA and are a source of nerve growth factor. Eur J Immunol. 1997; 27 2295-2301
108 Tam SY, Tsai M, Yamaguchi M, Yano K, Butterfield JH, Galli SJ. Expression of functional TrkA receptor tyrosine kinase in the mast cell line and in human mast cells. Blood. 1997; 90 1807-1820
109 Costa JJ, Demetri GD, Harrist TJ, Dvorak AM, Hayes DF, Merica EA, Menchaca DM, Gringeri AJ, Schwartz LB, Galli SJ. Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo. J Exp Med. 1996; 183 2681-2686
110 Lambiase A, Bonini S, Micera A, Magrini L, Bracci-Laudiero L, Aloe L. Increased plasma levels of nerve growth factor in vernal keratoconjunctivitis and relationship to conjunctival mast cells. Invest Ophthalmol Vis Sci. 1995; 36 2127-2132
111 Bonini S, Lambiase A, Angelucci F, Magrini L, Manni L, Aloe L. Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma. Proc Natl Acad Sci USA. 1996; 93 10955-10960
112 Aloe L. Nerve growth factor and neuroimmune responses: basic and clinical observations. Arch Physiol Biochem. 2001; 109 354-356
113 Welker P, Grabbe J, Grutzkau A, Henz BM. Effects of nerve growth factor (NGF) and other fibroblast-derived growth factors on immature human mast cells (HMC-1). Immunology. 1998; 94 310-317
114 Aloe L, Levi-Montalcini R. Mast cells increase in tissues of neonatal rats injected with the nerve growth factor. Brain Res. 1977; 133 358-366
115 Welker P, Grabbe J, Gibbs B, Zuberbier T, Henz BM. Nerve growth factor-beta induces mast-cell marker expression during in vitro culture of human umbilical cord blood cells. Immunology. 2000; 99 418-426
116 Kawamoto K, Okada T, Kannan Y, Ushio H, Matsumoto M, Matsuda H. Nerve growth factor prevents apoptosis of rat peritoneal mast cells through the trk proto-oncogene receptor. Blood. 1995; 86 4638-4644
117 Kanbe N, Kurosawa M, Miyachi Y, Kanbe M, Saitoh H, Matsuda H. Nerve growth factor prevents apoptosis of cord blood-derived human cultured mast cells synergistically with stem cell factor. Clin Exp Allergy. 2000; 30 1113-1120
118 Metz M, Botchkarev VA, Botchkareva NV, Welker P, Tobin DJ, Knop J, Maurer M, Paus R. Neurotrophin-3 regulates mast cell functions in neonatal mouse skin. Exp Dermatol. 2004; 13 273-281
119 Aloe L, Bracci-Laudiero L, Bonini S, Manni L. The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases. Allergy. 1997; 52 883-894
120 Ebadi M, Bashir RM, Heidrick ML, Hamada FM, Refaey HE, Hamed A, Helal G, Baxi MD, Cerutis DR, Lassi NK. Neurotrophins and their receptors in nerve injury and repair. Neurochem Int. 1997; 30 347-374
121 Bruni A, Bigon E, Boarato E, Mietto L, Leon A, Toffano G. Interaction between nerve growth factor and lysophosphatidylserine on rat peritoneal mast cells. FEBS Lett. 1982; 138 190-192
122 Pearce FL, Thompson HL. Some characteristics of histamine secretion from rat peritoneal mast cells stimulated with nerve growth factor. J Physiol. 1986; 372 379-393
123 Kawamoto K, Aoki J, Tanaka A, Itakura A, Hosono H, Arai H, Kiso Y, Matsuda H. Nerve growth factor activates mast cells through the collaborative interaction with lysophosphatidylserine expressed on the membrane surface of activated platelets. J Immunol. 2002; 168 6412-6419
124 Marshall JS, Gomi K, Blennerhassett MG, Bienenstock J. Nerve growth factor modifies the expression of inflammatory cytokines by mast cells via a prostanoid-dependent mechanism. J Immunol. 1999; 162 4271-4276
125 Bullock ED, Johnson Jr EM. Nerve growth factor induces the expression of certain cytokine genes and bcl-2 in mast cells. Potential role in survival promotion. J Biol Chem. 1996; 271 27500-27508
126 Raychaudhuri SP, Farber EM, Raychaudhuri SK. Role of nerve growth factor in RANTES expression by keratinocytes. Acta Derm Venereol. 2000; 80 247-250
127 Milner P, Bodin P, Guiducci S, Del Rosso A, Kahaleh MB, Matucci-Cerinic M, Burnstock G. Regulation of substance P mRNA expression in human dermal microvascular endothelial cells. Clin Exp Rheumatol. 2004; 22 S24-S27
128 Murphy PG, Borthwick LA, Altares M, Gauldie J, Kaplan D, Richardson PM. Reciprocal actions of interleukin-6 and brain-derived neurotrophic factor on rat and mouse primary sensory neurons. Eur J Neurosci. 2000; 12 1891-1899
129 Cafferty WB, Gardiner NJ, Das P, Qiu J, McMahon SB, Thompson SW. Conditioning injury-induced spinal axon regeneration fails in interleukin-6 knock-out mice. J Neurosci. 2004; 24 4432-4443
130 Lindholm D, Heumann R, Meyer M, Thoenen H. Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve. Nature. 1987; 330 658-659
131 Schulte-Herbruggen O, Nassenstein C, Lommatzsch M, Quarcoo D, Renz H, Braun A. Tumor necrosis factor-alpha and interleukin-6 regulate secretion of brain-derived neurotrophic factor in human monocytes. J Neuroimmunol. 2005; 160 204-209
132 Gadient RA, Cron KC, Otten U. Interleukin-1 beta and tumor necrosis factor-alpha synergistically stimulate nerve growth factor (NGF) release from cultured rat astrocytes. Neurosci Lett. 1990; 117 335-340
133 Hattori A, Tanaka E, Murase K, Ishida N, Chatani Y, Tsujimoto M, Hayashi K, Kohno M. Tumor necrosis factor stimulates the synthesis and secretion of biologically active nerve growth factor in non-neuronal cells. J Biol Chem. 1993; 268 2577-2582
134 Hattori A, Iwasaki S, Murase K, Tsujimoto M, Sato M, Hayashi K, Kohno M. Tumor necrosis factor is markedly synergistic with interleukin 1 and interferon-gamma in stimulating the production of nerve growth factor in fibroblasts. FEBS Lett. 1994; 340 177-180
135 Hattori A, Hayashi K, Kohno M. Tumor necrosis factor (TNF) stimulates the production of nerve growth factor in fibroblasts via the 55-kDa type 1 TNF receptor. FEBS Lett. 1996; 379 157-160
136 Olgart C, Frossard N. Human lung fibroblasts secrete nerve growth factor: effect of inflammatory cytokines and glucocorticoids. Eur Respir J. 2001; 18 115-121
137 Rost B, Hanf G, Ohnemus U, Otto-Knapp R, Groneberg DA, Kunkel G, Noga O. Monocytes of allergics and non-allergics produce, store and release the neurotrophins NGF, BDNF and NT-3. Regul Pept. 2005; 124 19-25
138 Torcia M, Bracci-Laudiero L, Lucibello M, Nencioni L, Labardi D, Rubartelli A, Cozzolino F, Aloe L, Garaci E. Nerve growth factor is an autocrine survival factor for memory B lymphocytes. Cell. 1996; 85 345-356
139 Lambiase A, Bracci-Laudiero L, Bonini S, Starace G, D’Elios MM, De Carli M, Aloe L. Human CD4+ T cell clones produce and release nerve growth factor and express high-affinity nerve growth factor receptors. J Allergy Clin Immunol. 1997; 100 408-414
140 Ehrhard PB, Erb P, Graumann U, Otten U. Expression of nerve growth factor and nerve growth factor receptor tyrosine kinase Trk in activated CD4-positive T-cell clones. Proc Natl Acad Sci USA. 1993; 90 10984-10988
141 Santambrogio L, Benedetti M, Chao MV, Muzaffar R, Kulig K, Gabellini N, Hochwald G. Nerve growth factor production by lymphocytes. J Immunol. 1994; 153 4488-4495
142 Moalem G, Gdalyahu A, Shani Y, Otten U, Lazarovici P, Cohen IR, Schwartz M. Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J Autoimmun. 2000; 15 331-345
143 Barouch R, Appel E, Kazimirsky G, Brodie C. Macrophages express neurotrophins and neurotrophin receptors. Regulation of nitric oxide production by NT-3. J Neuroimmunol. 2001; 112 72-77
144 Arredondo LR, Deng C, Ratts RB, Lovett-Racke AE, Holtzman DM, Racke MK. Role of nerve growth factor in experimental autoimmune encephalomyelitis. Eur J Immunol. 2001; 31 625-633
145 Muhallab S, Lundberg C, Gielen AW, Lidman O, Svenningsson A, Piehl F, Olsson T. Differential expression of neurotrophic factors and inflammatory cytokines by myelin basic protein-specific and other recruited T cells infiltrating the central nervous system during experimental autoimmune encephalomyelitis. Scand J Immunol. 2002; 55 264-273
146 Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R. Activated human T cells, B cells, and monocytes produce neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation?. J Exp Med. 1999; 189 865-870
147 Kerschensteiner M, Stadelmann C, Dechant G, Wekerle H, Hohlfeld R. Neurotrophic cross-talk between the nervous and immune systems: implications for neurological diseases. Ann Neurol. 2003; 53 292-304
148 Noga O, Englmann C, Hanf G, Grutzkau A, Guhl S, Kunkel G. Activation of the specific neurotrophin receptors TrkA, TrkB and influences the function of eosinophils. Clin Exp Allergy. 2002; 32 1348-1354
149 Noga O, Englmann C, Hanf G, Grutzkau A, Seybold J, Kunkel G. The production, storage and release of the neurotrophins nerve factor, brain-derived neurotrophic factor and neurotrophin-3 by peripheral eosinophils in allergics and non-allergics. Clin Exp Allergy. 2003; 33 649-654
150 Raap U, Goltz C, Deneka N, Bruder M, Renz H, Kapp A, Wedi B. Brain-derived neurotrophic factor is increased in atopic dermatitis and modulates eosinophil functions compared with that seen in nonatopic subjects. J Allergy Clin Immunol. 2005; 115 1268-1275
151 Kobayashi H, Gleich GJ, Butterfield JH, Kita H. Human eosinophils produce neurotrophins and secrete nerve growth immunologic stimuli. Blood. 2002; 99 2214-2220
152 Nassenstein C, Braun A, Erpenbeck VJ, Lommatzsch M, Schmidt S, Krug N, Luttmann W, Renz H, Virchow Jr JC. The neurotrophins nerve growth factor, brain-derived neurotrophic neurotrophin-3, and neurotrophin-4 are survival and activation eosinophils in patients with allergic bronchial asthma. J Exp Med. 2003; 198 455-467
153 la Sala A, Corinti S, Federici M, Saragovi HU, Girolomoni G. Ligand activation of nerve growth factor receptor TrkA protects monocytes from apoptosis. J Leukoc Biol. 2000; 68 104-110
154 Wei R, Jonakait GM. Neurotrophins and the anti-inflammatory agents interleukin-4 (IL-4), IL-10, IL-11 and transforming growth factor-beta1 (TGF-beta1) down-regulate T cell costimulatory molecules B7 and CD40 on cultured rat microglia. J Neuroimmunol. 1999; 95 8-18
155 Thompson SJ, Schatteman GC, Gown AM, Bothwell M. A monoclonal antibody against nerve growth factor receptor. Immunohistochemical analysis of normal and neoplastic human tissue. Am J Clin Pathol. 1989; 92 415-423
156 Pezzati. 1992; , #488
157 Labouyrie E, Parrens M, de Mascarel A, Bloch B, Merlio JP. Distribution of NGF receptors in normal and pathologic human lymphoid tissues. J Neuroimmunol. 1997; 77 161-173
158 Hosoi J, Murphy GF, Egan CL, Lerner EA, Grabbe S, Asahina A, Granstein RD. Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide. Nature. 1993; 363 159-163
159 Peters EM, Hansen MG, Overall RW, Nakamura M, Pertile P, Klapp BF, Arck PC, Paus R. Control of human hair growth by neurotrophins: brain-derived neurotrophic factor inhibits hair shaft elongation, induces catagen, and stimulates follicular transforming growth factor beta2 expression. J Invest Dermatol. 2005; 124 675-685
160 Lambiase A, Manni L, Bonini S, Rama P, Micera A, Aloe L. Nerve growth factor promotes corneal healing: structural, biochemical, and molecular analyses of rat and human corneas. Invest Ophthalmol Vis Sci. 2000; 41 1063-1069
161 Bonini S, Aloe L, Rama P, Lamagna A, Lambiase A. Nerve growth factor (NGF): an important molecule for trophism and healing of the ocular surface. Adv Exp Med Biol. 2002; 506 531-537
162 Tan MH, Bryars J, Moore J. Use of nerve growth factor to treat congenital neurotrophic corneal ulceration. Cornea. 2006; 25 352-355
163 Banks BE, Vernon CA, Warner JA. Nerve growth factor has anti-inflammatory activity in the rat hindpaw oedema test. Neurosci Lett. 1984; 47 41-45
164 Amico-Roxas M, Caruso A, Leone MG, Scifo R, Vanella A, Scapagnini U. Nerve growth factor inhibits some acute experimental inflammations. Arch Int Pharmacodyn Ther. 1989; 299 269-285
165 Micera A, Lambiase A, Puxeddu I, Aloe L, Stampachiacchiere B, Levi-Schaffer F, Bonini S. Nerve growth factor effect on human primary fibroblastic-keratocytes: possible mechanism during corneal healing. Exp Eye Res. 2006; 83 747-757
166 Kobayashi H, Mizisin AP. Nerve growth factor and neurotrophin-3 promote chemotaxis of mouse macrophages in vitro. Neurosci Lett. 2001; 305 157-160
167 Sawada J, Itakura A, Tanaka A, Furusaka T, Matsuda H. Nerve growth factor functions as a chemoattractant for mast cells through both mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. Blood. 2000; 95 2052-2058
168 Moser KV, Reindl M, Blasig I, Humpel C. Brain capillary endothelial cells proliferate in response to NGF, express NGF receptors and secrete NGF after inflammation. Brain Res. 2004; 13 1-2
169 Aloe L. Nerve growth factor, human skin ulcers and vascularization. Our experience. Prog Brain Res. 2004; 146 515-522
170 Faradji V, Sotelo J. Low serum levels of nerve growth factor in diabetic neuropathy. Acta Neurol Scand. 1990; 81 402-406
171 Kasayama S, Oka T. Impaired production of nerve growth factor in the submandibular gland of diabetic mice. Am J Physiol. 1989; 257 E400-E404
172 Ordonez G, Fernandez A, Perez R, Sotelo J. Low contents of nerve growth factor in serum and submaxillary gland of diabetic mice. A possible etiological element of diabetic neuropathy. J Neurol Sci. 1994; 121 163-166
173 Kannan Y, Ushio H, Koyama H, Okada M, Oikawa M, Yoshihara T, Kaneko M, Matsuda H. 2.5S nerve growth factor enhances survival, phagocytosis, and superoxide production of murine neutrophils. Blood. 1991; 77 1320-1325
174 Salis MB, Graiani G, Desortes E, Caldwell RB, Madeddu P, Emanueli C. Nerve growth factor supplementation reverses the impairment, induced by Type 1 diabetes, of hindlimb post-ischaemic recovery in mice. Diabetologia. 2004; 47 1055-1063
175 Toyoda M, Nakamura M, Makino T, Morohashi M. Localization and content of nerve growth factor in peripheral eosinophils of atopic dermatitis patients. Clin Exp Allergy. 2003; 33 950-955
176 Zuberbier T, Lelke A, Sänger K, Welker P, Guhl S, Henz BM. Comparison of mast cell precursors and cultured mast cells from the cord blood of children with Atopic and Nonatopic parents. Int Arch Allergy and Immunol. 2001; 124 304-306
177 Liang Y, Marcusson JA, Johansson O. Light and electron microscopic immunohistochemical observations of p75 nerve growth factor receptor-immunoreactive dermal nerves in prurigo nodularis. Arch Dermatol Res. 1999; 291 14-21
178 Grewe M, Vogelsang K, Ruzicka T, Stege H, Krutmann J. Neurotrophin-4 production by human epidermal keratinocytes: increased expression in atopic dermatitis. J Invest Dermatol. 2000; 114 1108-1112
179 Kinkelin I, Motzing S, Koltenzenburg M, Brocker EB. Increase in NGF content and nerve fiber sprouting in human contact eczema. Cell Tissue Res. 2000; 302 31-37
180 Johansson O, Liang Y, Emtestam L. Increased nerve growth factor- and tyrosine kinase A-like immunoreactivities in prurigo nodularis skin - an exploration of the cause of neurohyperplasia. Arch Dermatol Res. 2002; 293 614-619
181 Pincelli C, Fantini F, Massimi P, Girolomoni G, Seidenari S, Giannetti A. Neuropeptides in skin from patients with atopic dermatitis: an immunohistochemical study. Br J Dermatol. 1990; 122 745-750
182 Tobin DJ, Nabarro G, Baart de la Faille H, van Vloten WA, van der Putte SC, Schuurman HJ. Increased number of immunoreactive nerve fibers in atopic dermatitis. J Allergy Clin Immunol. 1992; 90 613-622
183 Ostlere LS, Cowen T, Rustin MH. Neuropeptides in the skin of patients with atopic dermatitis. Clin Exp Dermatol. 1995; 20 462-467
184 Sugiura H, Omoto M, Hirota Y, Danno K, Uehara M. Density and fine structure of peripheral nerves in various skin lesions of atopic dermatitis. Arch Dermatol Res. 1997; 289 125-131
185 Urashima R, Mihara M. Cutaneous nerves in atopic dermatitis. A histological, immunohistochemical and electron microscopic study. Virchows Arch. 1998; 432 363-370
186 Theodosiou M, Rush RA, Zhou XF, Hu D, Walker JS, Tracey DJ. Hyperalgesia due to nerve damage: role of nerve growth factor. Pain. 1999; 81 245-255
187 Horiuchi Y, Bae S, Katayama I. Nerve growth factor (NGF) and epidermal nerve fibers in atopic dermatitis model NC/Nga mice. J Dermatol Sci. 2005; 39 56-58
188 Hogan AD, Burks AW. Epidermal Langerhans' cells and their function in the skin immune system. Ann Allergy Asthma Immunol. 1995; 75 5-10
189 Taylor RS, Baadsgaard O, Hammerberg C, Cooper KD. Hyperstimulatory CD1a+CD1b+CD36+Langerhans cells are responsible for increased autologous T lymphocyte reactivity to lesional epidermal cells of patients with atopic dermatitis. J Immunol. 1991; 147 3794-3802
190 Naukkarinen A, Nickoloff BJ, Farber EM. Quantification of cutaneous sensory nerves and their substance P content in psoriasis [see comments]. J Invest Dermatol. 1989; 92 126-129
191 Jiang WY, Raychaudhuri SP, Farber EM. Double-labeled immunofluorescence study of cutaneous nerves in psoriasis. Int J Dermatol. 1998; 37 572-574
192 Pincelli C, Fantini F, Romualdi P, Sevignani C, Lesa G, Benassi L, Giannetti A. Substance P is diminished and vasoactive intestinal peptide is augmented in psoriatic lesions and these peptides exert disparate effects on the proliferation of cultured human keratinocytes. J Invest Dermatol. 1992; 98 421-427
193 Gaspari AA. Innate and adaptive immunity and the pathophysiology of psoriasis. J Am Acad Dermatol. 2006; 54 S67-S80
194 Aloe L, Simone MD, Properzi F. Nerve growth factor: a neurotrophin with activity on cells of the immune system. Microsc Res Tech. 1999; 45 285-291
195 Wrone-Smith T, Mitra RS, Thompson CB, Jasty R, Castle VP, Nickoloff BJ. Keratinocytes derived from psoriatic plaques are resistant to apoptosis compared with normal skin. Am J Pathol. 1997; 151 1321-1329
196 Fantini F, Magnoni C, Bracci-Laudiero L, Pincelli CT. Nerve growth factor is increased in psoriatic skin. J Invest Dermatol. 1995; 105 854-855
197 Raychaudhuri SP, Jiang WY, Farber EM. Psoriatic keratinocytes express high levels of nerve growth factor. Acta Derm Venereol. 1998; 78 84-86
198 Raychaudhuri SP, Sanyal M, Weltman H, Kundu-Raychaudhuri S. K252a, a high-affinity nerve growth factor receptor blocker, improves psoriasis: an in vivo study using the severe combined immunodeficient mouse-human skin model. J Invest Dermatol. 2004; 122 812-819
199 Lambiase A, Bonini S, Micera A, Tirassa P, Magrini L, Aloe L. Increased plasma levels of substance P in vernal keratoconjunctivitis. Invest Ophthalmol Vis Sci. 1997; 38 2161-2164
200 Virchow JC, Julius P, Lommatzsch M, Luttmann W, Renz H, Braun A. Neurotrophins are increased in bronchoalveolar lavage fluid after segmental allergen provocation. Am J Respir Crit Care Med. 1998; 158 2002-2005
201 Aloe L, Alleva E, Bohm A, Levi-Montalcini R. Aggressive behavior induces release of nerve growth factor from mouse salivary gland into the bloodstream. Proc Natl Acad Sci USA. 1986; 83 6184-6187
202 Aloe L, Alleva E, Fiore M. Stress and nerve growth factor: findings in animal models and humans. Pharmacol Biochem Behav. 2002; 73 159-166
203 Hadjiconstantinou M, McGuire L, Duchemin AM, Laskowski B, Kiecolt-Glaser J, Glaser R. Changes in plasma nerve growth factor levels in older adults associated with chronic stress. J Neuroimmunol. 2001; 116 102-106
204 Kimata H. Exposure to road traffic enhances allergic skin wheal responses and increases plasma neuropeptides and neurotrophins in patients with atopic eczema/dermatitis syndrome. Int J Hyg Environ Health. 2004; 207 45-49
205 Wright RJ, Cohen RT, Cohen S. The impact of stress on the development and expression of atopy. Curr Opin Allergy Clin Immunol. 2005; 5 23-29
206 Aloe L, Bracci-Laudiero L, Alleva E, Lambiase A, Micera A, Tirassa P. Emotional stress induced by parachute jumping enhances blood nerve growth factor levels and the distribution of nerve growth factor receptors in lymphocytes. Proc Natl Acad Sci USA. 1994; 91 10440-10444
207 Kawaguchi Y, Okada T, Konishi H, Fujino M, Asai J, Ito M. Reduction of the DTH response is related to morphological changes of Langerhans cells in mice exposed to acute immobilization stress. Clin Exp Immunol. 1997; 109 397-401
208 Flint MS, Depree KM, Rich BA, Tinkle SS. Differential regulation of sensitizer-induced inflammation and immunity by acute restraint stress in allergic contact dermatitis. J Neuroimmunol. 2003; 140 28-40
209 Ruiz MR, Quinones AG, Diaz NL, Tapia FJ. Acute immobilization stress induces clinical and neuroimmunological alterations in experimental murine cutaneous leishmaniasis. Br J Dermatol. 2003; 149 731-738
210 Nakano Y. Stress-induced modulation of skin immune function: two types of antigen-presenting cells in the epidermis are differentially regulated by chronic stress. Br J Dermatol. 2004; 151 50-64
211 Kimata H. Suckling reduces allergic skin responses and plasma levels of neuropeptide and neurotrophin in lactating women with atopic eczema/dermatitis syndrome. Int Arch Allergy Immunol. 2003; 132 380-383
212 Aloe L, Iannitelli A, Bersani G, Alleva E, Angelucci F, Maselli P, Manni L. Haloperidol administration in humans lowers plasma nerve growth factor level: evidence that sedation induces opposite effects to arousal. Neuropsychobiology 1997+ADs. 1997; 36 65-68
213 Graiani G, Emanueli C, Desortes E, Van Linthout S, Pinna A, Figueroa CD, Manni L, Madeddu P. Nerve growth factor promotes reparative angiogenesis and inhibits endothelial apoptosis in cutaneous wounds of Type 1 diabetic mice. Diabetologia. 2004; 47 1047-1054
214 Donnerer J. Regeneration of primary sensory neurons. Pharmacology. 2003; 67 169-181

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E. M. J. Peters

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