Journal
AMINO ACIDS
Volume 49, Issue 2, Pages 337-346Publisher
SPRINGER WIEN
DOI: 10.1007/s00726-016-2365-2
Keywords
L-Glutamine; Cortical spreading depression; Brain excitability; Immunoreactivity; Microglia; Anxiety-like behavior
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [445101/2014-8]
- Instituto Brasileiro de Neurociencias (IBN-Net/Finep) [4191]
- Capes [043/2013]
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In mammals, L-glutamine (Gln) can alter the glutamate-Gln cycle and consequently brain excitability. Here, we investigated in developing rats the effect of treatment with different doses of Gln on anxiety-like behavior, cortical spreading depression (CSD), and microglial activation expressed as Iba1-immunoreactivity. Wistar rats were suckled in litters with 9 and 15 pups (groups L-9 and L-15; respectively, normal size- and large size litters). From postnatal days (P) 7-27, the animals received Gln per gavage (250, 500 or 750 mg/kg/day), or vehicle (water), or no treatment (naive). At P28 and P30, we tested the animals, respectively, in the elevated plus maze and open field. At P30-35, we measured CSD parameters (velocity of propagation, amplitude, and duration). Fixative-perfused brains were processed for microglial immunolabeling with anti-IBA-1 antibodies to analyze cortical microglia. Rats treated with Gln presented an anxiolytic behavior and accelerated CSD propagation when compared to the water-and naive control groups. Furthermore, CSD velocity was higher (p < 0.001) in the L-15 compared to the L-9 condition. Gln treatment increased Iba1 immunolabeling both in the parietal cortex and CA1 hippocampus, indicating microglial activation. The Gln effect was dose-dependent for anxiety-like behavior and CSD in both litter sizes, and for microglial activation in the L-15 groups. Besides confirming previous electrophysiological findings (CSD acceleration after Gln), our data demonstrate for the first time a behavioral and microglial activation that is associated with early Gln treatment in developing animals, and that is possibly operated via changes in brain excitability.
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