http://www.fasebj.org/content/30/1_Supplement/915.10.short
+ Author Affiliations
Abstract
Alpha-lipoic acid (a-LA) is an antioxidant
that has been shown to ameliorate age-associated impairments of brain
and cardiovascular
functions as well as diabetic neuropathy in rodents
and humans. While the developing brain is highly metabolic and
therefore
potentially subject to periods of oxidative stress,
relatively little is known about the extent to which antioxidants
influence
the developing brain. Using the preclinical piglet
model, this exploratory study was designed to examine dose response
effects
of a-LA on growth, cognition and brain development.
Beginning at 2 d of age, 31 male pigs received one of three diets
formulated
to contain: control (CONT) [0 mg a-LA/100g], low
a-LA (LOW) [120 mg a-LA/100g], or high a-LA (HIGH) [240 mg a-LA/100g].
From
14 to 28 d of age, pigs were subjected to a spatial
T-maze behavioral assessment and neuroimaging procedures were performed
upon study completion at 31 d of age. No
differences due to diets were observed in measures of small intestine
weight or length,
or brain volumes. Additionally, there was no
observed interactive effect of diet x day for bodyweight measures.
Spatial T-maze
assessment did not reveal learning differences due
to diet, however HIGH-fed piglets exhibited faster (P = 0.02) latency to
choice compared with CONT and LOW-fed pigs on d 2
of the reversal phase. Neuroimaging analysis of microstructure using
diffusion
tensor imaging (DTI) revealed decreased (P = 0.01)
fractional anisotropy (FA) in the internal capsule of HIGH-fed pigs,
compared
with CONT- and LOW-fed pigs. Moreover, internal
capsule axial diffusivity values in HIGH-fed pigs were smaller (P <
0.01)
than CONT pigs, but were not different from LOW-fed
pigs. Tract-based spatial statistics (TBSS), which provide a voxel-wise
comparison of FA values along pre-determined fiber
tracts, revealed 4,116 voxels in which HIGH-fed pigs exhibited lower (P
< 0.05) FA values compared with CONT pigs.
Furthermore, TBSS revealed 7,105 voxels with lower (P < 0.05) FA
values in HIGH-fed
pigs compared with LOW-fed pigs. In both
comparisons, the largest voxel-wise FA value differences were localized
to areas
of the internal capsule, further corroborating DTI
observations. No TBSS differences were observed between CONT and LOW-fed
pigs. Taken together, the DTI and TBSS data suggest
an altered trajectory of brain white matter maturation in HIGH-fed
piglets.
In conclusion, lack of difference in growth,
behavioral assessment, and neuroimaging outcomes between LOW and CONT
pigs, indicate
low concentrations of a-LA support normal
development. Future research is warranted to determine if
supplementation of low
concentrations of a-LA may confer specific
neurodevelopmental benefits to piglets exposed to hypoxia, oxidative or
inflammatory
stress during development. However, since
supplementation at high concentrations may delay brain myelination
future research
should explore immunohistochemistry staining and/or
electron microscopy in conjunction with longitudinal follow-up to
better
understand the implications of these findings.
Support or Funding Information
Supported by Mead Johnson Nutrition.
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