Effect of pleiotrophin on glutamate-induced neurotoxicity in cultured hippocampal neurons

Asai, Hitomi; Morita, Shoko; Miyata, Seiji

doi:10.1002/cbf.1802

Cited by 9 publications

(6 citation statements)

References 40 publications

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“…For OGD, neuronal media was replaced with glucose-free DMEM (Invitrogen) supplemented with pericyte conditioned media with and without PTN neutralizing antibody, NI IgG, and mouse recombinant PTN as above in i), and then transferred in a humidified incubator chamber (Billups-Rothenberg, Inc.) with 1% O 2 at 37°C for 3 h. After 3 h, cells were removed from the chamber and processed for immunocytochemistry 24h later. For glutamate treatment, 10 μM glutamate were added to neuronal media as previously described 41 , and pericyte conditioned media, PTN neutralizing antibody, NI IgG, and PTN were added as above in i).…”

Section: Methodsmentioning

confidence: 99%

Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss

et al. 2019

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Pericytes are positioned between brain capillary endothelial cells, astrocytes and neurons. They degenerate in multiple neurological disorders. However, their role in the pathogenesis of these disorders remains debatable. Here, we generated an inducible pericyte-specific Cre line and crossed pericyte-specific Cre mice with iDTR mice carrying Cre-dependent human diphtheria toxin receptor (DTR). After pericyte ablation with diphtheria toxin, mice developed an acute blood-brain barrier (BBB) breakdown, severe loss of blood flow, and a rapid neuron loss associated with loss of pericyte-derived pleiotrophin (PTN), a neurotrophic growth factor. Intracerebroventricular PTN infusions prevented neuron loss in pericyte-ablated mice despite persistent circulatory changes. Silencing pericyte-derived Ptn rendered neurons vulnerable to ischemic and excitotoxic injury. Our data demonstrate a rapid neurodegeneration cascade linking pericyte loss to acute circulatory collapse and loss of PTN neurotrophic support. These findings could have implications for the pathogenesis and treatment of neurological disorders associated with pericyte loss and/or neurovascular dysfunction.

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Section: Methodsmentioning

confidence: 99%

Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss

et al. 2019

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“…PTN is a secreted cellular factor related to the ECM, and its expression levels are elevated in epileptic rats . PTN, as an important neuroregulator, plays various roles in the central nervous system, including neuronal survival, differentiation, and migration . Focal adhesion based cell ECM interactions are essential for cell anchoring and migration.…”

Section: Resultsmentioning

confidence: 99%

Identification of Curcumin Targets in the Brain of Epileptic Mice Using DARTS

Zhang,

Lin,

et al. 2024

ACS Omega

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Curcumin, a compound derived from turmeric, is traditionally utilized in East Asian medicine for treating various health conditions, including epilepsy. Despite its involvement in numerous cellular signaling pathways, the specific mechanisms and targets of curcumin in epilepsy treatment have remained unclear.Our study focused on identifying the primary targets and functional pathways of curcumin in the brains of epileptic mice. Using drug affinity responsive target stabilization (DARTS) and affinity chromatography, we identified key targets in the mouse brain, revealing 232 and 70 potential curcumin targets, respectively. Bioinformatics analysis revealed a strong association of these proteins with focal adhesions and cytoskeletal components. Further experiments using DARTS, along with immunofluorescence staining and cell migration assays, confirmed curcumin's ability to regulate the dynamics of focal adhesions and influence cell migration. This study not only advances our understanding of curcumin's role in epilepsy treatment but also serves as a model for identifying therapeutic targets in neurological disorders.

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“… 57 Similarly, menin resulted in opposite consequences in female patients with MEN1 syndrome and pNEN with or without estrogen exposure, 59 as well as in resistant prostate cancer with or without androgen receptor. 58 Moreover, PTN was associated with the expression of several proteins or enzymes 61 , 62 , 63 that are displayed as different expression patterns in BON1 and QGP1, 63 , 64 , 65 such as MGMT, 64 MAP2, 63 and MDM. 65 Therefore, the molecular factors that are abundant in QGP1 but rare in BON1 cells, may interact with menin to regulate PTN expression and metastasis in patients with pNEN and in cell lines.…”

Section: Discussionmentioning

confidence: 99%

The link between menin and pleiotrophin in the tumor biology of pancreatic neuroendocrine neoplasms

Boulant

Stanifer

et al. 2022

Cancer Science

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MEN1, which encodes menin protein, is the most frequently mutated gene in pancreatic neuroendocrine neoplasms (pNEN). Pleiotrophin (PTN) has been reported as a downstream factor of menin that promotes metastasis in different tumor entities. In this study, the effect of menin and its link to PTN were assessed using features of pNEN cells and the outcome of patients with pNEN. The expression levels of menin and PTN in tissues from patients with pNEN were examined using qRT‐PCR and western blot and compared with their metastasis status. Functional assays, including transwell migration/invasion and scratch wound‐healing assays, were performed on specifically designed CRISPR/Cas9‐mediated MEN1‐knockout (MEN1‐KO) pNEN cell lines (BON1MEN1‐KO and QGP1MEN1‐KO) to study the metastasis of pNEN. Among 30 patients with menin‐negative pNEN, 21 revealed a strong protein expression of PTN. This combination was associated with metastasis and shorter disease‐free survival. Accordingly, in BON1MEN1‐KO and QGP1MEN1‐KO cells, PTN protein expression was positively associated with enhanced cell migration and invasion, which could be reversed using PTN silencing. PTN is a predicting factor of metastatic behavior of menin‐deficient‐pNEN. In vitro, menin is able to both promote and suppress the metastasis of pNEN by regulating PTN expression depending on the tumoral origin of pNEN cells.

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Effect of pleiotrophin on glutamate-induced neurotoxicity in cultured hippocampal neurons

Cited by 9 publications

References 40 publications

Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss

Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss

Identification of Curcumin Targets in the Brain of Epileptic Mice Using DARTS

The link between menin and pleiotrophin in the tumor biology of pancreatic neuroendocrine neoplasms

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