Erythropoietin targets parvalbumin-positive inhibitory neurons and microglia to promote plasticity in the thalamic reticular nucleus
Erythropoietin (EPO) and its receptor (EPOR) promote neuroprotection and neural plasticity. The effects of recombinant human (rh)EPO have been extensively studied in the hippocampus, where significant effects on inhibitory neurons have been recently discovered. However, little is known about the eff...
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| Hauptverfasser: | , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
1 October 2026
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| In: |
Neuropharmacology
Year: 2026, Jahrgang: 297, Pages: 1-13 |
| ISSN: | 1873-7064 |
| DOI: | 10.1016/j.neuropharm.2026.111025 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.neuropharm.2026.111025 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S002839082600198X 
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| Verfasserangaben: | Yaiza Gramuntell, Patrycja Klimzack, Yasmina Curto, Julia Alcaide, Erica Garcia-Verellen, Marta Perez-Rando, Klaus-Armin Nave, Hannelore Ehrenreich, Juan Nacher |
| Zusammenfassung: | Erythropoietin (EPO) and its receptor (EPOR) promote neuroprotection and neural plasticity. The effects of recombinant human (rh)EPO have been extensively studied in the hippocampus, where significant effects on inhibitory neurons have been recently discovered. However, little is known about the effects of EPO on the thalamus, particularly on the thalamic reticular nucleus (TRN), a GABAergic structure regulating corticothalamic communication, which is altered in different CNS disorders. Here, we investigated EPOR expression and the impact of chronic rhEPO treatment on TRN neurons, their plasticity-related molecules, and glial populations, as well as the projections of these neurons to thalamic excitatory nuclei. EPOR was expressed by all Gad1+/Pvalb + TRN neurons, along with subsets of astrocytes and microglia. Young male mice treated with rhEPO for 3 weeks exhibited increased density of PV + neurons and VGLUT2+ puncta in the TRN, while the density of VGLUT1+ and VGAT + puncta remained unaffected. The activity marker FosB was significantly decreased in PV+, but not PV-cells, of the TRN. No changes were detected in the volume of the TRN, PSA-NCAM expression, the immunofluorescence intensity of Wisteria floribunda-labeled perineuronal nets or the density of PV + puncta in the ventral posterolateral and lateral posterior excitatory nuclei. Interestingly, microglial density was significantly reduced, with no changes in astroglial cells. These findings indicate that rhEPO directly targets TRN PV-expressing neurons, modulating their maturation, physiology and connectivity and has important effects on microglial cells. Altogether, our results suggest that EPO contributes to thalamic circuit plasticity, further supporting its potential therapeutic relevance in neuropsychiatric disorders. |
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| Beschreibung: | Online verfügbar: 15. Mai 2026, Artikelversion: 22. Mai 2026 Gesehen am 31.07.2026 |
| Beschreibung: | Online Resource |
| ISSN: | 1873-7064 |
| DOI: | 10.1016/j.neuropharm.2026.111025 |