Immune control of the basal ganglia network: Interleukin-17 as a key modulator of striatal synaptic plasticity
The basal ganglia (BG) network exerts a key role in the integration of cortical inputs and is fundamental to motor learning, behavior, emotional responses, and cognitive functions. Little is known about how immune cells and soluble immune mediators influence BG activity. Interleukin-17A (IL-17A) is...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
|
| Series: | Neurobiology of Disease |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125002104 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849304223764709376 |
|---|---|
| author | Andrea Mancini Laura Bellingacci Jacopo Canonichesi Miriam Sciaccaluga Alfredo Megaro Elisa Zianni Maria De Carluccio Marilena Pariano Edoardo Emiliano Alessandro Tozzi Cinzia Costa Teresa Zelante Luigina Romani Maria Teresa Viscomi Fabrizio Gardoni Paolo Calabresi Lucilla Parnetti Massimiliano Di Filippo |
| author_facet | Andrea Mancini Laura Bellingacci Jacopo Canonichesi Miriam Sciaccaluga Alfredo Megaro Elisa Zianni Maria De Carluccio Marilena Pariano Edoardo Emiliano Alessandro Tozzi Cinzia Costa Teresa Zelante Luigina Romani Maria Teresa Viscomi Fabrizio Gardoni Paolo Calabresi Lucilla Parnetti Massimiliano Di Filippo |
| author_sort | Andrea Mancini |
| collection | DOAJ |
| description | The basal ganglia (BG) network exerts a key role in the integration of cortical inputs and is fundamental to motor learning, behavior, emotional responses, and cognitive functions. Little is known about how immune cells and soluble immune mediators influence BG activity. Interleukin-17A (IL-17A) is in the spotlight for its emerging role as a neuromodulator of cortical synaptic transmission and plasticity in physiological and pathological conditions. However, its role at the level of subcortical structures such as the BG circuit is still unclear. In this study, we demonstrate that striatal medium spiny neurons (MSNs) highly express IL-17RA and that the IL-17 axis contributes to the physiological expression of synaptic plasticity in these cells. Indeed, long-term potentiation (LTP) induction was significantly reduced in mice lacking IL-17A or IL-17RA. This effect might rely on an altered glutamatergic transmission, as synaptic expression of NMDAR subunit GluN2B is reduced in mice lacking IL-17A. At the same time, exposure to high concentrations of IL-17A was found to impair LTP induction through modulation of NMDAR currents. These results suggest a dual effect of this cytokine on striatal synaptic plasticity, showing the IL-17 axis as a key neuromodulator of the BG circuit, with potential implications in the pathogenesis of neuroinflammatory and neuropsychiatric disorders. |
| format | Article |
| id | doaj-art-ae42cfd754ec4a6aa4b9e8df4a2c4bb9 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-ae42cfd754ec4a6aa4b9e8df4a2c4bb92025-08-20T03:55:48ZengElsevierNeurobiology of Disease1095-953X2025-09-0121310699410.1016/j.nbd.2025.106994Immune control of the basal ganglia network: Interleukin-17 as a key modulator of striatal synaptic plasticityAndrea Mancini0Laura Bellingacci1Jacopo Canonichesi2Miriam Sciaccaluga3Alfredo Megaro4Elisa Zianni5Maria De Carluccio6Marilena Pariano7Edoardo Emiliano8Alessandro Tozzi9Cinzia Costa10Teresa Zelante11Luigina Romani12Maria Teresa Viscomi13Fabrizio Gardoni14Paolo Calabresi15Lucilla Parnetti16Massimiliano Di Filippo17Section of Neurology and Laboratory of Experimental Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, ItalySection of Physiology and Biochemistry, Department of Medicine and Surgery, University of Perugia, Perugia, ItalySection of Neurology and Laboratory of Experimental Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, ItalySection of Neurology and Laboratory of Experimental Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, ItalySection of Neurology and Laboratory of Experimental Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, ItalyDepartment of Neuroscience and Neurorehabilitation, IRCCS San Raffaele, Rome, italy; Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, ItalySection of Neurophysiopathology, “S.M. della Misericordia” Hospital, Perugia, ItalySection of Neurology and Laboratory of Experimental Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, ItalySection of Physiology and Biochemistry, Department of Medicine and Surgery, University of Perugia, Perugia, ItalySection of Neurology and Laboratory of Experimental Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; Section of Neurophysiopathology, “S.M. della Misericordia” Hospital, Perugia, ItalySection of Pathology, Department of Medicine and Surgery, University of Perugia, Perugia, ItalySection of Pathology, Department of Medicine and Surgery, University of Perugia, Perugia, ItalySection of Histology and Embryology, Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy; Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, ItalyDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy; Section of Neurology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalySection of Neurology and Laboratory of Experimental Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, ItalySection of Neurology and Laboratory of Experimental Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; Corresponding author at: Section of Neurology, Dept. of Medicine and Surgery, University of Perugia, Italy.The basal ganglia (BG) network exerts a key role in the integration of cortical inputs and is fundamental to motor learning, behavior, emotional responses, and cognitive functions. Little is known about how immune cells and soluble immune mediators influence BG activity. Interleukin-17A (IL-17A) is in the spotlight for its emerging role as a neuromodulator of cortical synaptic transmission and plasticity in physiological and pathological conditions. However, its role at the level of subcortical structures such as the BG circuit is still unclear. In this study, we demonstrate that striatal medium spiny neurons (MSNs) highly express IL-17RA and that the IL-17 axis contributes to the physiological expression of synaptic plasticity in these cells. Indeed, long-term potentiation (LTP) induction was significantly reduced in mice lacking IL-17A or IL-17RA. This effect might rely on an altered glutamatergic transmission, as synaptic expression of NMDAR subunit GluN2B is reduced in mice lacking IL-17A. At the same time, exposure to high concentrations of IL-17A was found to impair LTP induction through modulation of NMDAR currents. These results suggest a dual effect of this cytokine on striatal synaptic plasticity, showing the IL-17 axis as a key neuromodulator of the BG circuit, with potential implications in the pathogenesis of neuroinflammatory and neuropsychiatric disorders.http://www.sciencedirect.com/science/article/pii/S0969996125002104 |
| spellingShingle | Andrea Mancini Laura Bellingacci Jacopo Canonichesi Miriam Sciaccaluga Alfredo Megaro Elisa Zianni Maria De Carluccio Marilena Pariano Edoardo Emiliano Alessandro Tozzi Cinzia Costa Teresa Zelante Luigina Romani Maria Teresa Viscomi Fabrizio Gardoni Paolo Calabresi Lucilla Parnetti Massimiliano Di Filippo Immune control of the basal ganglia network: Interleukin-17 as a key modulator of striatal synaptic plasticity Neurobiology of Disease |
| title | Immune control of the basal ganglia network: Interleukin-17 as a key modulator of striatal synaptic plasticity |
| title_full | Immune control of the basal ganglia network: Interleukin-17 as a key modulator of striatal synaptic plasticity |
| title_fullStr | Immune control of the basal ganglia network: Interleukin-17 as a key modulator of striatal synaptic plasticity |
| title_full_unstemmed | Immune control of the basal ganglia network: Interleukin-17 as a key modulator of striatal synaptic plasticity |
| title_short | Immune control of the basal ganglia network: Interleukin-17 as a key modulator of striatal synaptic plasticity |
| title_sort | immune control of the basal ganglia network interleukin 17 as a key modulator of striatal synaptic plasticity |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125002104 |
| work_keys_str_mv | AT andreamancini immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT laurabellingacci immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT jacopocanonichesi immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT miriamsciaccaluga immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT alfredomegaro immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT elisazianni immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT mariadecarluccio immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT marilenapariano immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT edoardoemiliano immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT alessandrotozzi immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT cinziacosta immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT teresazelante immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT luiginaromani immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT mariateresaviscomi immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT fabriziogardoni immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT paolocalabresi immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT lucillaparnetti immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity AT massimilianodifilippo immunecontrolofthebasalganglianetworkinterleukin17asakeymodulatorofstriatalsynapticplasticity |