Abstract | BACKGROUND: METHODS: We analyzed the following in control and hyperammonemic rats, treated or not with sulforaphane: (1) microglia and astrocytes activation by immunohistochemistry, (2) markers of pro-inflammatory (M1) (IL-1β, IL-6) and anti-inflammatory (M2) microglia (Arg1, YM-1) by Western blot, (3) membrane expression of GABA, AMPA, and NMDA receptors using the BS3 cross-linker, and (4) spatial learning using the radial maze. RESULTS: The results reported show that hyperammonemia induces astrocytes and microglia activation in the hippocampus, increasing pro-inflammatory cytokines IL-1β and IL-6. This is associated with altered membrane expression of AMPA, NMDA, and GABA receptors which would be responsible for altered neurotransmission and impairment of spatial learning in the radial maze. Treatment with sulforaphane promotes microglia differentiation from pro-inflammatory M1 to anti-inflammatory M2 phenotype and reduces activation of astrocytes in hyperammonemic rats. This reduces neuroinflammation, normalizes membrane expression of glutamate and GABA receptors, and restores spatial learning in hyperammonemic rats. CONCLUSIONS:
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Authors | Vicente Hernández-Rabaza, Andrea Cabrera-Pastor, Lucas Taoro-González, Michele Malaguarnera, Ana Agustí, Marta Llansola, Vicente Felipo |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 13
Pg. 41
(Feb 16 2016)
ISSN: 1742-2094 [Electronic] England |
PMID | 26883214
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- Cytokines
- Glial Fibrillary Acidic Protein
- Isothiocyanates
- Receptors, Neurotransmitter
- Sulfoxides
- sulforaphane
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Topics |
- Animals
- Anti-Inflammatory Agents
(pharmacology, therapeutic use)
- Body Weight
(drug effects)
- Cytokines
(metabolism)
- Disease Models, Animal
- Encephalitis
(drug therapy, etiology)
- Gene Expression Regulation
(drug effects)
- Glial Fibrillary Acidic Protein
(metabolism)
- Hippocampus
(metabolism, pathology)
- Hyperammonemia
(complications, pathology)
- In Vitro Techniques
- Isothiocyanates
(pharmacology, therapeutic use)
- Learning Disabilities
(drug therapy, etiology, pathology)
- Male
- Maze Learning
(drug effects)
- Neuroglia
(drug effects, metabolism)
- Rats
- Rats, Wistar
- Receptors, Neurotransmitter
(metabolism)
- Spatial Learning
(drug effects, physiology)
- Sulfoxides
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