Abstract | BACKGROUND: METHODS: We analyzed in control and hyperammonemic rats, treated or not with sulforaphane, (a) learning in the Y maze; (b) motor coordination in the beam walking; (c) glutamate-NO-cGMP pathway and extracellular GABA by microdialysis; (d) microglial activation, by analyzing by immunohistochemistry or Western blot markers of pro-inflammatory (M1) (IL-1b, Iba-1) and anti-inflammatory (M2) microglia (Iba1, IL-4, IL-10, Arg1, YM-1); and (e) membrane expression of the GABA transporter GAT-3. RESULTS:
Hyperammonemia induces activation of astrocytes and microglia in the cerebellum as assessed by immunohistochemistry. Hyperammonemia-induced neuroinflammation is associated with increased membrane expression of the GABA transporter GAT-3, mainly in activated astrocytes. This is also associated with increased extracellular GABA in the cerebellum and with motor in-coordination and impaired learning ability in the Y maze. Sulforaphane promotes polarization of microglia from the M1 to the M2 phenotype, reducing IL-1b and increasing IL-4, IL-10, Arg1, and YM-1 in the cerebellum. This is associated with astrocytes deactivation and normalization of GAT-3 membrane expression, extracellular GABA, glutamate- nitric oxide-cGMP pathway, and learning and motor coordination. CONCLUSIONS:
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Authors | Vicente Hernandez-Rabaza, Andrea Cabrera-Pastor, Lucas Taoro-Gonzalez, Alba Gonzalez-Usano, Ana Agusti, Tiziano Balzano, Marta Llansola, Vicente Felipo |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 13
Issue 1
Pg. 83
(Apr 18 2016)
ISSN: 1742-2094 [Electronic] England |
PMID | 27090509
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- GABA Plasma Membrane Transport Proteins
- Isothiocyanates
- Sulfoxides
- gamma-Aminobutyric Acid
- sulforaphane
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Topics |
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Blotting, Western
- Cell Membrane
(metabolism)
- Cerebellum
- Disease Models, Animal
- GABA Plasma Membrane Transport Proteins
(biosynthesis)
- Hepatic Encephalopathy
(complications, metabolism)
- Hyperammonemia
(etiology, metabolism, physiopathology)
- Immunohistochemistry
- Inflammation
(metabolism)
- Isothiocyanates
(pharmacology)
- Male
- Maze Learning
(drug effects, physiology)
- Microdialysis
- Microglia
(drug effects, metabolism)
- Motor Activity
(drug effects, physiology)
- Rats
- Rats, Wistar
- Sulfoxides
- gamma-Aminobutyric Acid
(metabolism)
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