Emotional stress induced by parachute jumping enhances blood nerve growth factor levels and the distribution of nerve growth factor receptors in lymphocytes.

Aloe, Luigi; Bracci-Laudiero, Luisa; Alleva, Enrico; Lambìase, Alessandro; Micera, Alessandra; Tirassa, Paola

doi:10.1073/pnas.91.22.10440

Cited by 238 publications

(144 citation statements)

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“…16,17 While direct sampling of the brain is not possible in humans, peripheral blood cell gene expression may provide a surrogate indicator of differential response to stress and subsequent PTSD. Supporting this tenet, acute psychological stress is associated with immune activation, 18 and persistent immune alterations have been linked with chronic PTSD. 19,[20][21][22] Additionally, recent microarray studies in human CNS disorders (multiple sclerosis, stroke and seizure) as well as rodent models of such disease suggest specific gene expression signatures in PBMCs.…”

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confidence: 99%

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

et al. 2005

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Trauma survivors show marked differences in the severity and persistence of post-traumatic stress disorder (PTSD) symptoms. Early symptoms subside in most, but persist as acute and chronic PTSD in a significant minority. The underlying molecular mechanisms or outcome predictors determining these differences are not known. Molecular markers for identifying any mental disorder are currently lacking. Gene expression profiling during the triggering and development of PTSD may be informative of its onset and course. We used oligonucleotide microarrays to measure peripheral blood mononuclear cell (PBMC) gene expression of trauma survivors at the emergency room and 4 months later. Gene expression signatures at both time points distinguished survivors who met DSM-IV diagnostic criteria for PTSD at 1 and 4 months, from those who met no PTSD criterion. Expression signatures at both time points correlated with the severity of each of the three PTSD symptom clusters assessed 4 months following exposure among all survivors. Results demonstrate a general reduction in PBMCs' expression of transcription activators among psychologically affected trauma survivors. Several differentiating genes were previously described as having a role in stress response. These findings provide initial evidence that peripheral gene expression signatures following trauma identify an evolving neuropsychiatric disorder and are informative of its key clinical features and outcome. Replications in larger samples, as well as studies focusing on specific markers within the signatures discovered, are warranted to confirm and extend the diagnostic utility and pathogenetic implications of our results. Molecular Psychiatry (2005) 10, 500-513.

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Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

et al. 2005

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“…Of particular interest also is the observation that the level of NGF is enhanced in the nervous, endocrine, and immune systems in response to psychologic stress (19,(136)(137)(138), leading to the hypothesis that NGF is implicated in homeostatic responses (6). Recent observations in both rodents and in man, demonstrating that drugs which interfere with arousal behavior lower basal NGF, seem to support this hypothesis.…”

Section: Ngf and Allergymentioning

confidence: 73%

“…The hypothesis that the alteration of circulating NGF levels might be associated with allergic reactions was proposed in 1992 in a study of the effect of psychologic stress induced in young soldiers by parachute jumping. Tliis study revealed that the plasma of a young soldier suffering from allergy contained a high level of NGF (19). The consistency and validity of this hypothesis were conviticingly demonstrated by studying patients affected by vernal keratoconjunctivitis (VKC) and by later investigations of patients affected by other types of allergies (25,26,134).…”

Section: Ngf and Allergymentioning

confidence: 87%

“…The functional significance of the large amounts of NGF observed in the mouse SG is not fully understood, though recent studies reported by our laboratory and other laboratories have demonstrated that the NGF produced in the SG is released into the bloodstream after intraspecific aggressive behavior (15, 16) and acts not only on nerve cells and chromaffin cells, but also on several immune cells such as mast cells (MC) and lymphocytes (17)(18)(19)(20). These observations led to the hypothesis that salivary NGF may play a functional role in these cells.…”

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The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases

Aloe

Bracci-Laudiero

Бонини

et al. 1997

Allergy

200

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Numerous studies published in the last 10–15 years have shown that nerve growth factor (NGF), a polypeptide originally discovered in connection with its neurotrophic activity, also acts on cells of the immune system. NGF has been found in various immune organs including the spleen, lymph nodes, and thymus, and cells such as mast cells, eosinophils, and B and T cells. The circulating levels of NGF increase in inflammatory responses, in various autoimmune diseases, in parasitic infections, and in allergic diseases. Stress‐related events both in animal models and in man also result in an increase of NGF, suggesting that this molecule is involved in neuroendocrine functions. The rapid release of NGF is part of an alerting signal in response to either psychologically stressful or anxiogenic conditions in response to homeostatic alteration. Thus, the inflammation and stress‐induced increase in NGF might alone or in association with other biologic mediators induce the activation of immune cells during immunologic insults. A clearer understanding of the role of NGF in these events may be useful to identify the mechanisms implicated in certain neuroimmune and immune dysfunctions.

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“…23,24,50 The absence of p75 LNGFR is a common feature of immune or hematopoietic cells. 27 However, the coexpression of p75 LNGFR and TrkA has been detected in certain immune cells such as human B lymphocytes 28,51 and bone marrow-derived mouse mast cells. 52 In addition, bone marrow stromal cells were found to be immunoreactive for all NT receptors including p75 LNGFR .…”

Section: Discussionmentioning

confidence: 99%

Expression of Neurotrophins and their Receptors in Human Bone Marrow

Labouyrie

Dubus

Groppi

et al. 1999

The American Journal of Pathology

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101

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The expression of neurotrophins and their receptors, the low-affinity nerve growth factor receptor (p75 LNGFR ) and the Trk receptors (TrkA , TrkB, and TrkC) , was investigated in human bone marrow from 16 weeks fetal age to adulthood. Using reverse transcription-polymerase chain reaction , all transcripts encoding for catalytic and truncated human TrkB or TrkC receptors were detected together with trkAI transcripts , whereas trkAII transcripts were found only in control nerve tissues. Transcripts for the homologue of the rat truncated TrkC(ic113) receptor were identified for the first time in human tissue. Stromal adventitial reticular cells were found immunoreactive for all neutrophin receptors. In contrast, hematopoietic cell types were not immunoreactive for p75 LNGFR Nerve growth factor (NGF) 1 is the prototype of a family of related neurotrophic factors known as neurotrophins (NT), which also includes brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4, also called neurotrophin-5 or NT-5 in humans) (reviewed in Lindsay et al 2 ). NT are trophic factors for the growth, differentiation, and survival of specific subsets of neurons in the developing and mature nervous system. 2 NT can interact with two classes of receptors with distinct ligand affinity and specificity. The low-affinity nerve growth factor receptor, p75 LNGFR , binds all known NT. 3,4 Tyrosine kinase receptors of the Trk family are essential components of NT high-affinity binding sites that trigger neuronal survival, growth, and differentiation. 5 TrkA is the preferred receptor for NGF 6,7 but has a lower efficiency for NT-3 or NT-4/5. TrkB is bound by BDNF and NT-4 and, to a lesser extent, by 9 TrkC is characterized by a unique ligand, NT-3. 10 In some cell lines, TrkA is sufficient to form high-affinity binding sites through homodimerization, 7 whereas p75 LNGFR potentiates TrkA activation by NGF in the PC12 cell line. 11 Variants of tyrosine kinase receptors (TK ϩ ) with insertions in either the extracellular domain (ECD) or the tyrosine kinase domain have been identified for trkA 12,13 and trkC [13][14][15][16] in both human and rat.Truncated receptors lacking the kinase domain (TK Ϫ ) have been described for TrkB and TrkC but not for TrkA. [15][16][17][18] These receptors may function as dominant negative isoforms or immunoadhesins. 13,19,20 Both TK ϩ and TK Ϫ receptors have been detected in neurons while only truncated TrkB and TrkC isoforms have been detected primarily in nonneuronal cells. [15][16][17][18]21 The expression of functional NGF receptors has been detected in several bone marrow-derived cells such as monocytes, 22 mastocytes, 23,24 and B or T cell clones. [25][26][27][28] Among its pleiotropic effects, NGF induces platelet shape changes, 29 triggers monocyte cytotoxic activity, 22 and induces basophilic cell differentiation 30 -32 and mast cell development and degranulation. 24,33 However, NGF receptors have not been consistently detected on bone marrow cells. Although trkA and p75 L...

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Emotional stress induced by parachute jumping enhances blood nerve growth factor levels and the distribution of nerve growth factor receptors in lymphocytes.

Cited by 238 publications

References 46 publications

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors

The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases

Expression of Neurotrophins and their Receptors in Human Bone Marrow

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