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Updated: Nov 29, 2025
Author Spotlight: In Vitro Co-Culture Model for Studying Microglia-Neuronal Interactions in Disease Conditions
Published on: July 26, 2024
Role of RPTPβ/ζ in neuroinflammation and microglia-neuron communication
Rosalía Fernández-Calle1, Milagros Galán-Llario1, Esther Gramage1
1Departamento de Ciencias Farmacéuticas y de La Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28925, Alcorcón, Madrid, Spain.
Abstract:
Pleiotrophin (PTN) is a cytokine that is upregulated in different neuroinflammatory disorders. Using mice with transgenic PTN overexpression in the brain (Ptn-Tg), we have found a positive correlation between iNos and Tnfα mRNA and Ptn mRNA levels in the prefrontal cortex (PFC) of LPS-treated mice. PTN is an inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ, which is mainly expressed in the central nervous system. We aimed to test if RPTPβ/ζ is involved in the modulation of neuroinflammatory responses using specific inhibitors of RPTPβ/ζ (MY10 and MY33-3). Treatment with MY10 potentiated LPS-induced microglial responses in the mouse PFC. Surprisingly, MY10 caused a decrease in LPS-induced NF-κB p65 expression, suggesting that RPTPβ/ζ may be involved in a novel mechanism of potentiation of microglial activation independent of the NF-κB p65 pathway. MY33-3 and MY10 limited LPS-induced nitrites production and iNos increases in BV2 microglial cells. SH-SY5Y neuronal cells were treated with the conditioned media from MY10/LPS-treated BV2 cells. Conditioned media from non-stimulated and from LPS-stimulated BV2 cells increased the viability of SH-SY5Y cultures. RPTPβ/ζ inhibition in microglial cells disrupted this neurotrophic effect of microglia, suggesting that RPTPβ/ζ plays a role in the neurotrophic phenotype of microglia and in microglia-neuron communication.
Insights
Pleiotrophin (PTN) influences neuroinflammation by inhibiting Receptor Protein Tyrosine Phosphatase beta/zeta (RPTPβ/ζ). Inhibiting RPTPβ/ζ in microglia impacts neurotrophic signaling and microglia-neuron communication.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Pleiotrophin (PTN) is a cytokine implicated in neuroinflammatory disorders.
- PTN inhibits Receptor Protein Tyrosine Phosphatase beta/zeta (RPTPβ/ζ), a key protein in the central nervous system.
Purpose of the Study:
- To investigate the role of RPTPβ/ζ in neuroinflammation modulation.
- To explore the impact of RPTPβ/ζ inhibition on microglial activation and neurotrophic signaling.
Main Methods:
- Utilized transgenic mice overexpressing PTN (Ptn-Tg) and lipopolysaccharide (LPS) treatment.
- Administered specific RPTPβ/ζ inhibitors (MY10, MY33-3) to mice and BV2 microglial cells.
- Assessed mRNA levels (iNos, Tnfα, Ptn), protein expression (NF-κB p65), nitrite production, and neuronal cell viability.
Main Results:
- RPTPβ/ζ inhibition potentiated LPS-induced microglial responses but decreased NF-κB p65 expression, suggesting a novel pathway.
- Inhibitors reduced LPS-induced nitrites and iNos in microglial cells.
- RPTPβ/ζ inhibition disrupted the neurotrophic effect of microglia on SH-SY5Y neuronal cells, impairing microglia-neuron communication.
Conclusions:
- RPTPβ/ζ plays a dual role in neuroinflammation, potentially mediating microglial activation independently of NF-κB.
- RPTPβ/ζ is crucial for the neurotrophic function of microglia and effective microglia-neuron communication.
