RESUMO
Branched-chain amino acids (BCAAs) are known to be neurorestorative after traumatic brain injury (TBI). Despite clinically significant improvements in severe TBI patients given BCAAs after TBI, the approach is largely an unrecognized option. Further, TBI continues to be the most common cause of morbidity and mortality in adolescents and adults. To date, no study has evaluated whether BCAAs can be preventive or neuroprotective if taken before a TBI. We hypothesized that if BCAAs were elevated in the circulation before TBI, the brain would readily access the BCAAs and the severity of injury would be reduced. Before TBI induction with a standard weight-drop method, 50 adult mice were randomized into groups that were shams, untreated, and pre-treated, post-treated, or pre- + post-treated with BCAAs. Pre-treated mice received BCAAs through supplemented water and were dosed by oral gavage 45 min before TBI induction. All mice underwent beam walking to assess motor recovery, and the Morris water maze assessed cognitive function post-injury. On post-injury day 14, brains were harvested to assess levels of astrocytes and microglia with glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1) immunohistochemistry, respectively. Pre-treated and pre- +post-treated mice exhibited significantly better motor recovery and cognitive function than the other groups. The pre- + post-treated group had the best overall memory performance, whereas the pre-treated and post-treated groups only had limited improvements in memory compared to untreated animals. Pre- + post-treated brains had levels of GFAP that were similar to the sham group, whereas the pre-only and post-only groups showed increases. Although trends existed, no meaningful changes in IBA-1 were detected. This is the first study, animal or human, to demonstrate that BCAA are neuroprotective and substantiates their neurorestorative benefits after TBI, most likely through the important roles of BCAAs to glutamate homeostasis.
RESUMO
Background: Human milk contains both arachidonic acid (ARA) and docosahexaenoic acid (DHA). Supplementation of infant formula with ARA and DHA results in fatty acid (FA) profiles, neurodevelopmental outcomes, and immune responses in formula-fed infants that are more like those observed in breastfed infants. Consequently, ARA and DHA have been historically added together to infant formula. This study investigated the impact of ARA or DHA supplementation alone or in combination on tissue FA incorporation, immune responses, and neurodevelopment in the young pig. Methods: Male pigs (N = 48 total) received one of four dietary treatments from postnatal day (PND) 2-30. Treatments targeted the following ARA/DHA levels (% of total FA): CON (0.00/0.00), ARA (0.80/0.00), DHA (0.00/0.80), and ARA+DHA (0.80/0.80). Plasma, red blood cells (RBC), and prefrontal cortex (PFC) were collected for FA analysis. Blood was collected for T cell immunophenotyping and to quantify a panel of immune outcomes. Myelin thickness in the corpus callosum was measured by transmission electron microscopy and pig movement was measured by actigraphy. Results: There were no differences in formula intake or growth between dietary groups. DHA supplementation increased brain DHA, but decreased ARA, compared with all other groups. ARA supplementation increased brain ARA compared with all other groups but did not affect brain DHA. Combined supplementation increased brain DHA levels but did not affect brain ARA levels compared with the control. Pigs fed ARA or ARA+DHA exhibited more activity than those fed CON or DHA. Diet-dependent differences in activity suggested pigs fed ARA had the lowest percent time asleep, while those fed DHA had the highest. No differences were observed for immune or myelination outcomes. Conclusion: Supplementation with ARA and DHA did not differentially affect immune responses, but ARA levels in RBC and PFC were reduced when DHA was provided without ARA. Supplementation of either ARA or DHA alone induced differences in time spent asleep, and ARA inclusion increased general activity. Therefore, the current data support the combined supplementation with both ARA and DHA in infant formula and raise questions regarding the safety and nutritional suitability of ARA or DHA supplementation individually.
RESUMO
BACKGROUND: Queen bee acid (QBA; 10-hydroxy-2-decenoic acid) is the predominant fatty acid in royal jelly (RJ) and has activity at estrogen receptors, which affect brain function and body composition. However, few, long-term studies have assessed QBA effects in brain health and body composition. METHODS: Primary hippocampal neurons were treated with QBA (0-30 µM) and challenged with glutamate or hypoxia. QBA was fed to aged, male Sprague-Dawley rats (12-24 mg/kg/day) and to adult male and female Balb/C mice (30-60 mg/kg/day) for ≥3.5 months. Rats were evaluated in a behavioral test battery of brain function. Mice were measured for fat and muscle composition, as well as bone density. RESULTS: QBA increased neuron growth and protected against glutamate challenge and hypoxia challenge. Rats receiving QBA had reduced anxiety-like behavior, increased body weight, and better maintenance of body weight with age. Mice receiving QBA exhibited increased body weight, muscle mass, and adiposity in males, and increased bone density, but decreased adiposity, in females. CONCLUSIONS: QBA is an active component of RJ that promotes the growth and protection of neurons, reduces anxiety-like phenotypes, and benefits bone, muscle and adipose tissues in a sex-dependent manner, which further implicates estrogen receptors in the effects of QBA.