Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine
Midkine (MK) is a cytokine that modulates amphetamine-induced striatal astrogliosis, suggesting a possible role of MK in neuroinflammation induced by amphetamine. To test this hypothesis, we studied astrogliosis and microglial response induced by amphetamine (10 mg/kg i.p. four times, every 2 h) in...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/9894504 |
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| author | Marta Vicente-Rodríguez Rosalía Fernández-Calle Esther Gramage Carmen Pérez-García María P. Ramos Gonzalo Herradón |
| author_facet | Marta Vicente-Rodríguez Rosalía Fernández-Calle Esther Gramage Carmen Pérez-García María P. Ramos Gonzalo Herradón |
| author_sort | Marta Vicente-Rodríguez |
| collection | DOAJ |
| description | Midkine (MK) is a cytokine that modulates amphetamine-induced striatal astrogliosis, suggesting a possible role of MK in neuroinflammation induced by amphetamine. To test this hypothesis, we studied astrogliosis and microglial response induced by amphetamine (10 mg/kg i.p. four times, every 2 h) in different brain areas of MK−/− mice and wild type (WT) mice. We found that amphetamine-induced microgliosis and astrocytosis are enhanced in the striatum of MK−/− mice in a region-specific manner. Surprisingly, LPS-induced astrogliosis in the striatum was blocked in MK−/− mice. Since striatal neuroinflammation induced by amphetamine-type stimulants correlates with the cognitive deficits induced by these drugs, we also tested the long-term effects of periadolescent amphetamine treatment (3 mg/kg i.p. daily for 10 days) in a memory task in MK−/− and WT mice. Significant deficits in the Y-maze test were only observed in amphetamine-pretreated MK−/− mice. The data demonstrate for the first time that MK is a novel modulator of neuroinflammation depending on the inflammatory stimulus and the brain area considered. The data indicate that MK limits amphetamine-induced striatal neuroinflammation. In addition, our data demonstrate that periadolescent amphetamine treatment in mice results in transient disruption of learning and memory processes in absence of endogenous MK. |
| format | Article |
| id | doaj-art-e1c9a1f752e8441cbd51b4e1a171051b |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-e1c9a1f752e8441cbd51b4e1a171051b2025-02-03T06:01:33ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/98945049894504Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by MidkineMarta Vicente-Rodríguez0Rosalía Fernández-Calle1Esther Gramage2Carmen Pérez-García3María P. Ramos4Gonzalo Herradón5Pharmacology Lab, Department of Pharmaceutical and Health Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, SpainPharmacology Lab, Department of Pharmaceutical and Health Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, SpainPharmacology Lab, Department of Pharmaceutical and Health Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, SpainPharmacology Lab, Department of Pharmaceutical and Health Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, SpainBiochemistry and Molecular Biology Lab, Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, SpainPharmacology Lab, Department of Pharmaceutical and Health Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, SpainMidkine (MK) is a cytokine that modulates amphetamine-induced striatal astrogliosis, suggesting a possible role of MK in neuroinflammation induced by amphetamine. To test this hypothesis, we studied astrogliosis and microglial response induced by amphetamine (10 mg/kg i.p. four times, every 2 h) in different brain areas of MK−/− mice and wild type (WT) mice. We found that amphetamine-induced microgliosis and astrocytosis are enhanced in the striatum of MK−/− mice in a region-specific manner. Surprisingly, LPS-induced astrogliosis in the striatum was blocked in MK−/− mice. Since striatal neuroinflammation induced by amphetamine-type stimulants correlates with the cognitive deficits induced by these drugs, we also tested the long-term effects of periadolescent amphetamine treatment (3 mg/kg i.p. daily for 10 days) in a memory task in MK−/− and WT mice. Significant deficits in the Y-maze test were only observed in amphetamine-pretreated MK−/− mice. The data demonstrate for the first time that MK is a novel modulator of neuroinflammation depending on the inflammatory stimulus and the brain area considered. The data indicate that MK limits amphetamine-induced striatal neuroinflammation. In addition, our data demonstrate that periadolescent amphetamine treatment in mice results in transient disruption of learning and memory processes in absence of endogenous MK.http://dx.doi.org/10.1155/2016/9894504 |
| spellingShingle | Marta Vicente-Rodríguez Rosalía Fernández-Calle Esther Gramage Carmen Pérez-García María P. Ramos Gonzalo Herradón Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine Mediators of Inflammation |
| title | Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine |
| title_full | Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine |
| title_fullStr | Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine |
| title_full_unstemmed | Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine |
| title_short | Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine |
| title_sort | midkine is a novel regulator of amphetamine induced striatal gliosis and cognitive impairment evidence for a stimulus dependent regulation of neuroinflammation by midkine |
| url | http://dx.doi.org/10.1155/2016/9894504 |
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