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.

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.

Brain effects of the lectin from Canavalia ensiformis in adult rats previously suckled in favorable and unfavorable conditions: A spreading depression and microglia immunolabeling study.

OBJECTIVE: To evaluate in adult rats, previously suckled under favorable and unfavorable conditions, the brain electrophysiological and microglial effects of the treatment early in life with the lectin (ConA) from Canavalia ensiformis. METHODS: Male Wistar newborn rats (n = 89) were suckled under favorable or unfavorable conditions, represented by litters with 6-7 pups or 12-14 pups (groups N6 and N12, respectively). From postnatal days 5-24, they were treated intraperitoneally with 1 or 10 mg/kg ConA (groups L1 and L10, respectively), or with saline solution (group Sal), or no treatment (group Naïve). At 90-120 days of age, cortical spreading depression (CSD) was recorded at two parietal points for 4 hours, and CSD parameters (velocity of propagation and amplitude and duration of the DC slow potential change) were measured. Fixative-perfused brain sections were reacted with anti-Iba1 antibodies to quantify immunolabeled microglia. RESULTS: Compared with the control groups, ConA-treated animals dose-dependently presented with reduced CSD propagation velocities and increased amplitude and duration of the CSD slow potential change. Microglia Iba-1 immunoreactivity was lower in both nutritional groups treated with ConA, in comparison with the control groups. The CSD hemisphere presented with higher immunoreactivity compared with the CSD-free hemisphere. DISCUSSION: Attenuation in CSD propagation and microglia reaction was associated in adulthood with ConA treatment during brain development, indicating that the lectin can affect the electrophysiological and microglial development, and suggesting long-lasting protective action of the lectin on the rat brain, which is not impeded by the unfavorable suckling condition.

Spreading depression features and Iba1 immunoreactivity in the cerebral cortex of developing rats submitted to treadmill exercise after treatment with monosodium glutamate.

Physical exercise and excessive consumption of monosodium glutamate (MSG) can affect the morphological and electrophysiological organization of the brain during development. However, the interaction of both factors remains unclear. We analyzed the effect of this interaction on the excitability-related phenomenon known as cortical spreading depression (CSD) and the microglial reaction expressed as Iba1-immunolabeled cells in the rat motor cortex. MSG (2g/kg or 4g/kg) was administered every other day during the first 14 postnatal days. Treadmill exercise started at 21-23 days of life and lasted 3 weeks, 5 days/week, for 30min/day. At 45-60 days, CSD was recorded for 4h at two cortical points and the CSD parameters (velocity, amplitude, and duration of the negative potential change) calculated. Confirming previous observations, exercised rats presented with lower CSD velocities (3.29±0.18mm/min) than the sedentary group (3.80±0.18mm/min; P<0.05). MSG increased CSD velocities in the exercised rats compared to saline-treated and exercised animals in a dose-dependent manner (3.49±0.19, 4.05±0.18, and 3.27±0.26 for 2g/kg MSG, 4g/kg MSG, and saline, respectively; P<0.05). The amplitude (ranging from 14.3±5.9 to 18.7±6.2mV) and duration (46.7±11.1 to 60.5±11.6s) of the negative slow potential shift of the CSD were similar in all groups. Both exercise and MSG treatment increased Iba1 immunolabeling. The results confirm that physical exercise decelerates CSD propagation. However, it does not impede the CSD-accelerating action of MSG. These effects were accompanied by a cortical microglia reaction. Therefore, the data suggest that treadmill exercise early in life can influence the development of cortical electrical activity.

Neonatal treatment with monosodium glutamate lastingly facilitates spreading depression in the rat cortex.

AIMS: Monosodium glutamate (MSG) is a neuroexcitatory amino acid used in human food to enhance flavor. MSG can affect the morphological and electrophysiological organization of the brain. This effect is more severe during brain development. Here, we investigated the electrophysiological and morphological effects of MSG in the developing rat brain by characterizing changes in the excitability-related phenomenon of cortical spreading depression (CSD) and microglial reaction. MAIN METHODS: From postnatal days 1-14, Wistar rat pups received 2 or 4 g/kg MSG (groups MSG-2 and MSG-4, respectively; n=9 in each group), saline (n=10) or no treatment (naïve group; n=5) every other day. At 45-60 days, CSD was recorded on two cortical points for 4h. The CSD parameters velocity, and amplitude and duration of the negative potential change were calculated. Fixative-perfused brain sections were immunolabeled with anti-IBA-1 antibodies to identify and quantify cortical microglia. KEY FINDINGS: MSG-4 rats presented significantly higher velocities (4.59 ± 0.34 mm/min) than the controls (saline, 3.84 ± 0.20mm/min; naïve, 3.71 ± 0.8mm/min) and MSG-2 group (3.75 ± 0.10mm/min). The amplitude (8.8 ± 2.2 to 11.2 ± 1.9 mV) and duration (58.2 ± 7.1 to 73.6 ± 6.0s) of the negative slow potential shift was similar in all groups. MSG-treatment dose-dependently increased the microglial immunolabeling. SIGNIFICANCE: The results demonstrate a novel, dose-dependent action of MSG in the developing brain, characterized by acceleration of CSD and significant microglial reaction in the cerebral cortex. The CSD effect indicates that MSG can influence cortical excitability, during brain development, as evaluated by CSD acceleration. Data suggest caution when consuming MSG, especially in developing organisms.

Equilíbrio dinâmico: influência das restrições ambientais / Dynamic equilibrium: influence of environmental constrainsts

Os objetivos do estudo foram: (a) verificar estratégias locomotoras utilizadas quando crescentesrestrições ambientais são aplicadas a crianças; e (b) relacionar comportamento motor nestas condiçõescom características intrínsecas dos participantes. Dois experimentos foram delineados variando a altura (solo e 39 cm no experimento 1 e 39 e 120 cm no experimento 2) onde crianças (3 a 10 anos no experimento 1 e 3 a 7 anos no experimento 2) andaram. Em ambos os experimentos, as crianças apresentaram preferência no posicionamento do pé (pé plano), aumento na quantidade de passadas e diminuição no comprimento das passadas com aumento da altura. Variáveis intrínsecas aos participantese posicionamento do pé explicaram a variabilidade no comportamento locomotor. Pode-se inferir que o equilíbrio dinâmico é uma importante variável no controle motor durante tarefa locomotora em ambiente complexo...

The aims of this study were: (a) to verify the locomotor strategies used when increased environmental constraints are applied to children; and (b) to relate the locomotor behavior within these conditions with the participants intrinsic characteristics. Two experiments were designed varying the height (ground and 39 cm in Experiment 1 and 39 cm and 120 cm in Experiment 2) were children (3 to 10years old in Experiment 1 and 3 to 7 years old in Experiment 2) walked. In both studies, children presentedfoot position preference (flat foot), increased step amount and decreased step length related to the increase in height. ParticipantÆs intrinsic variables and foot position explained the locomotor behavior variability. It can be infered that the dynamic equilibrium is an important variable in motor control during locomotor task in complex environment...