Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.07.16.206094

Masitinib mediates TGF-Beta1 and Nitric Oxide Secretion and Ameliorates MPTP/Microglia-Induced Degeneration of Differentiated SH-SY5Y Cells

Goksu Erol, A. Y.·Akinci, E.·Kocanci, F. G.·Akcakale, F.·Demir Dora, D.·Uysal, H.
View original source ↗Export metadata ↓

Abstract

IntroductionMicroglia secretome includes not only growth factors and cytokines which support neuronal survival, it includes neurotoxic cytokines/enzymes, as well. MPTP is a neurotoxin which has degenerative effects on SH-SY5Y neuroblastoma cells. Masitinib mesylate is a tyrosine kinase inhibitor which has been shown to have beneficial effects in neurodegenerative diseases. AimWe first aimed to determine the most efficient microglial cell conditioned medium in terms of neurodegenerative effect. Next, we investigated the possible protective/therapeutic effects of masitinib against MPTP/microglia-induced degeneration of differentiated (d)-SH-SY5Y cells, and the role of transforming growth factor (TGF)-{beta}1 and nitric oxide (NO) in these events. Material-MethodsNon-stimulated/LPS-stimulated microglia cells were treated with masitinib or its solvent, DMSO. With or without MPTP-d-SH-SY5Y cell cultures were exposed to the conditioned media (CM) from microglia cell cultures, followed by cell survival analysis. Immunofluorescence staining of microglia and d-SH-SY5Y cells were performed with anti-CD-11b and anti-PGP9.5 antibody, respectively. TGF-{beta}1/NO concentrations in CM of microglia/d-SH-SY5Y cell culture were measured. ResultsThe initial 24 hrs CM of non-stimulated microglia cell culture was found to be the most detrimental microglial medium with lowest survival rates of treated d-SH-SY5Y cells. The toxicity of 48 and 72 hrs CM on d-SH-SY5Y cells were both lower than that of 24 hrs CM. Masitinib (0.5 {micro}M), significantly prevented MPTP-related cell degeneration of d-SH-SY5Y cells. It also decreased the degenerative effects of both non-induced/LPS-induced microglia CM on with or without MPTP-d-SH-SY5Y cells. Although NO levels in microglia CM showed a negative correlation with survival rates of treated d-SH-SY5Y cells, a positive correlation was seen between TGF-{beta}1 concentrations in microglial CM and rates of treated d-SH-SY5Y cell survival. ConclusionMasitinib ameliorates viability of with/without MPTP-d-SH-SY5Y cells. It does not only reverse the degenerative effects of its solvent, DMSO, but also prevents the degenerative effects of microglial secretions and MPTP. We suggest that masitinib begins to act as a neuroprotective agent via mediating TGF-{beta}1 and NO secretion, as neurons are exposed to over-activated microglia or neurotoxins.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Goksu Erol, A. Y., Akinci, E., Kocanci, F. G., Akcakale, F., Demir Dora, D., Uysal, H.. 2020-07-16. Masitinib mediates TGF-Beta1 and Nitric Oxide Secretion and Ameliorates MPTP/Microglia-Induced Degeneration of Differentiated SH-SY5Y Cells. https://doi.org/10.1101/2020.07.16.206094

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗
bioRxiv2026

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗
bioRxiv2026

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗