Platelet-derived nerve growth factor supports the survival of cholinergic neurons in organotypic rat brain slices

Kniewallner, Kathrin M.; Grimm, Natalia; Humpel, Christian

doi:10.1016/j.neulet.2014.05.033

Cited by 17 publications

(15 citation statements)

References 21 publications

(36 reference statements)

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“…Previous studies have reported that NGF can be induced by cholinergic stimuli (da Penha Berzaghi et al, 1993; Lapchak et al, 1993; Mahmoud et al, 2015), and in turn NGF can promote cholinergic nerve growth (Collins, 1984; Collins and Dawson, 1983; Kniewallner et al, 2014), consistent with our results. While the major receptor for NGF is TrkA, another neurotrophin receptor p75NTR can bind to NGF and pro-NGF (Howard et al, 2013).…”

Section: Discussionsupporting

confidence: 93%

Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling

et al. 2017

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Summary Within the gastrointestinal stem cell niche, nerves help to regulate both normal and neoplastic stem cell dynamics. Here, we reveal the mechanisms underlying the cancer-nerve partnership. We find that Dclk1+ tuft cells and nerves are the main sources of acetylcholine (ACh) within the gastric mucosa. Cholinergic stimulation of the gastric epithelium induced nerve growth factor (NGF) expression, and in turn NGF overexpression within gastric epithelium expanded enteric nerves and promoted carcinogenesis. Ablation of Dclk1+ cells or blockade of NGF/Trk signaling inhibited epithelial proliferation and tumorigenesis in a muscarinic acetylcholine receptor-3 (M3R)-dependent manner, in part through suppression of Yes-Associated Protein (YAP) function. This feed-forward ACh-NGF axis activates the gastric cancer niche and offers a compelling target for tumor treatment and prevention.

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Section: Discussionsupporting

confidence: 93%

Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling

et al. 2017

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“…Moreover, NGF levels in peripheral blood only partially reflect actual level and activities of NGF in the CNS, since NGF is mainly produced in the CNS, but also produced, stored, and released in several immune cells like monocytes and lymphocytes (129) and platelets (130–134). Recent evidence points to a sufficient correlation between peripheral and central nervous NGF levels, whereas this correlation was only shown in healthy controls but not in schizophrenia patients (51).…”

Section: Discussionmentioning

confidence: 99%

Nerve Growth Factor Serum Levels Are Associated With Regional Gray Matter Volume Differences in Schizophrenia Patients

et al. 2019

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Numerous neuroimaging studies have revealed structural brain abnormalities in schizophrenia patients. There is emerging evidence that dysfunctional nerve growth factor (NGF) signaling may contribute to structural brain alterations found in these patients. In this pilot study, we investigated whether there was a correlation between NGF serum levels and gray matter volume (GMV) in schizophrenia patients. Further, we investigated whether there was an overlap between the correlative findings and cross-sectional GMV differences between schizophrenia patients (n = 18) and healthy controls (n = 19). Serum NGF was significantly correlated to GMV in the left prefrontal lobe, the left midcingulate cortex, and the brainstem in schizophrenia patients. However, we did not find any correlations of NGF serum levels with GMV in healthy controls. Schizophrenia patients showed smaller GMV than healthy controls in brain regions located in the bilateral limbic system, bilateral parietal lobe, bilateral insula, bilateral primary auditory cortex, left frontal lobe, and bilateral occipital regions. In a conjunction analysis, GMV in the left midcingulate cortex (MCC) appears negatively correlated to NGF serum levels in the group of schizophrenia patients and also to be reduced compared to healthy controls. These results suggest an increased vulnerability of schizophrenia patients to changes in NGF levels compared to healthy controls and support a role for NGF signaling in the pathophysiology of schizophrenia. As our pilot study is exploratory in nature, further studies enrolling larger sample sizes will be needed to further corroborate our findings and to investigate the influence of additional covariates.

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“…These four growth factors were selected mostly as representative biomarkers of the composition of the platelet lysates used in our study, and because they are known to support neuronal survival [38–40]. Platelet lysates contain other neurotrophic factors, such as transforming growth factor-ß, basic fibroblast growth factor, hepatocyte growth factor [3], nerve growth factor [41], and stromal cell-derived factor 1-a [5]. These factors may contribute in a synergistic way to the functional activity of the neuroprotective platelet biotherapy [4].…”

Section: Discussionmentioning

confidence: 99%

The neuroprotective activity of heat-treated human platelet lysate biomaterials manufactured from outdated pathogen-reduced (amotosalen/UVA) platelet concentrates

et al. 2019

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BackgroundEffective neurorestorative therapies of neurodegenerative diseases must be developed. There is increasing interest in using human platelet lysates, rich in neurotrophic factors, as novel disease-modifying strategy of neurodegeneration. To ensure virus safety, pathogen reduction treatments should be incorporated in the preparation process of the platelet concentrates used as source material. We therefore investigated whether platelet concentrates (PC) pathogen-inactivated using a licensed photo-inactivation treatment combining photosensitive psoralen (amotosalen) and UVA irradiation (Intercept) can serve as source material to prepare platelet lysates with preserved neuroprotective activity in Parkinson’s disease models.MethodsIntercept treated-PCs were centrifuged, when reaching expiry day (7 days after collection), to remove plasma and platelet additive solution. The platelet pellet was re-suspended and concentrated in phosphate buffer saline, subjected to 3 freeze-thaw cycles (− 80 °C/37 °C) then centrifuged to remove cell debris. The supernatant was recovered and further purified, or not, by heat-treatment as in our previous investigations. The content in proteins and neurotrophic factors was determined and the toxicity and neuroprotective activity of the platelet lysates towards LUHMES cells or primary cortical/hippocampal neurons were assessed using ELISA, flow cytometry, cell viability and cytotoxicity assays and proteins analysis by Western blot.ResultsPlatelet lysates contained the expected level of total proteins (ca. 7–14 mg/mL) and neurotrophic factors. Virally inactivated and heat-treated platelet lysates did not exert detectable toxic effects on neither Lund human mesencephalic dopaminergic LUHMES cell line nor primary neurons. When used at doses of 5 and 0.5%, they enhanced the expression of tyrosine hydroxylase and neuron-specific enolase in LUHMES cells and did not significantly impact synaptic protein expression in primary neurons, respectively. Furthermore, virally-inactivated platelet lysates tested were found to exert very strong neuroprotection effects on both LUHMES and primary neurons exposed to erastin, an inducer of ferroptosis cell death.ConclusionOutdated Intercept pathogen-reduced platelet concentrates can be used to prepare safe and highly neuroprotective human heat-treated platelet pellet lysates. These data open reassuring perspectives in the possibility to develop an effective biotherapy using virally-inactivated platelet lysates rich in functional neurotrophins for neuroregenerative medicine, and for further bio-industrial development. However, the data should be confirmed in animal models.Graphical abstract

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Platelet-derived nerve growth factor supports the survival of cholinergic neurons in organotypic rat brain slices

Cited by 17 publications

References 21 publications

Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling

Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling

Nerve Growth Factor Serum Levels Are Associated With Regional Gray Matter Volume Differences in Schizophrenia Patients

The neuroprotective activity of heat-treated human platelet lysate biomaterials manufactured from outdated pathogen-reduced (amotosalen/UVA) platelet concentrates

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