title: Neonatal L-glutamine modulates anxiety-like behavior, cortical spreading depression, and microglial immunoreactivity: analysis in developing rats suckled on normal size- and large size litters.
abstract: 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 L9and L15; 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 L15compared to the L9condition. 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 L15groups. 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.
authors.affiliation: Department of Nutrition, Universidade Federal de Pernambuco, Recife, PE, 50670901, Brazil.
authors.forename: Denise Sandrelly Cavalcanti
authors.initials: DS
authors.lastname: de Lima
authors.affiliation: Department of Nutrition, Universidade Federal de Pernambuco, Recife, PE, 50670901, Brazil.
authors.forename: Elian da Silva
authors.initials: ED
authors.lastname: Francisco
authors.affiliation: Department of Nutrition, Universidade Federal de Pernambuco, Recife, PE, 50670901, Brazil.
authors.forename: Cássia Borges
authors.initials: CB
authors.lastname: Lima
authors.affiliation: Department of Nutrition, Universidade Federal de Pernambuco, Recife, PE, 50670901, Brazil. guedes.rca@gmail.com.
authors.forename: Rubem Carlos Araújo
authors.initials: RC
authors.lastname: Guedes
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D013181:Cortical Spreading Depression / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005973:Glutamine / Q000008:administration & dosage / Q000494:pharmacology*; D008098:Litter Size; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D017208:Rats, Wistar
chemical_list: D005973:Glutamine
keywords: Anxiety-like behavior; Brain excitability; Cortical spreading depression; Immunoreactivity; L-Glutamine; Microglia