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Neuroinflammation increases GABAergic tone and impairs cognitive and motor function in hyperammonemia by increasing GAT-3 membrane expression. Reversal by sulforaphane by promoting M2 polarization of microglia

2016; BioMed Central; Volume: 13; Issue: 1 Linguagem: Inglês

10.1186/s12974-016-0549-z

1742-2094

Vicente Hernández‐Rabaza, Andrea Cabrera‐Pastor, Lucas Taoro‐González, Alba González‐Usano, Ana Agustí, Tiziano Balzano, Marta Llansola, Vicente Felipo,

Neurogenesis and neuroplasticity mechanisms

Hyperammonemia induces neuroinflammation and increases GABAergic tone in the cerebellum which contributes to cognitive and motor impairment in hepatic encephalopathy (HE). The link between neuroinflammation and GABAergic tone remains unknown. New treatments reducing neuroinflammation and GABAergic tone could improve neurological impairment. The aims were, in hyperammonemic rats, to assess whether: (a) Enhancing endogenous anti-inflammatory mechanisms by sulforaphane treatment reduces neuroinflammation and restores learning and motor coordination. (b) Reduction of neuroinflammation by sulforaphane normalizes extracellular GABA and glutamate-NO-cGMP pathway and identify underlying mechanisms. (c) Identify steps by which hyperammonemia-induced microglial activation impairs cognitive and motor function and how sulforaphane restores them.