Thiamine deficiency results in biochemical and metabolic dysfunctions that affect
various regions of the brain, originating cognitive and motor impairments. Thiamin,
vitamin B1, is an essential nutrient for nerve tissue. When phosphorylated, it gives
rise to different forms, such as thiamine pyrophosphate, which acts as a key enzyme
cofactor in cellular energy metabolism. Beriberi, Wernicke encephalopathy (EW) and
Wernicke-Korsacoff syndrome (SWK) are the major deficiency diseases in humans.
The initial lesions of EW are bleeding into the gray matter around the third and fourth
ventricles and the Sylvius aqueduct. Central nervous system (CNS) regions involved
in polyencephalomalacia (PEM) are varied and contradictory, but are affected from
cortical areas to deep regions such as the midbrain and thalamus. At these sites,
there is typically degeneration and neuronal necrosis, with adjacent involvement of
astrocytic and inflammatory changes. Little is known about the molecular and cellular
mechanisms of degeneration and death of neurons, however, it is considered that the
process related to thiamine deficiency is initiated by metabolic defects in the
mitochondria, with consequent establishment of oxidative stress. In this work we
aimed to determine different parameters related to thiamine deficiency in the CNS in
an in vivo model, in order to evaluate the association of lesions and behavioral
changes in the model animals and the design of efficient neuroprotective strategies.
The dietary deficiency model in combination with thiamine antagonist injections,
pyriamine, was used in the study. The animals were treated for 9 days, divided into 6
treatment groups: control (Cont), pyrylamine (Ptd), pyrylamine and trolox (Ptd + Tr),
pyritiamine and dimethylsulfoxide (Ptd + Dmso), Trolox (Tr) and Dimethylsulfoxide
Dmso). Mice subjected to the thiamine deficiency model (Ptd group) exhibited a
significant reduction in body weight gain and feed intake after 9 days of treatment.
Thiamine deficient animals presented behavioral alterations such as reduction in
motor coordination and exploratory activity. Trolox and Dmso attenuated these
effects. In the Ptd group there was a decrease in cell viability in important areas, such
as cerebral cortex, hippocampus and thalamus. However, histopathology showed
lesions in the thalamus and brain stem, such as hemorrhage, astrocytic vacuolization
and spongiosis. In the groups Ptd + Trt and Ptd + Dmso there was a marked
attenuation of these lesions. In the western blot evaluations, the Ptd group showed
increased phosphorylation of p38MAPK in the cerebral cortex and thalamus. The Ptd
+ Tr group totally blocked this effect in both encephalic structures. And the group (Ptd
+ Dmso) reduced the increase in p38MAPK phosphorylation, but less intensely than
Trolox. There was an increase in the expression of HO-1 in the Ptd group, already in
the Ptd + Trt and Ptd + Dmso groups. No change occurred in the induction of
increase in HO-1 expression. These data suggest that in the thiamine deficiency
model with pyriamine, animals develop neurological and metabolic changes, possibly
associated with oxidative stress and inflammation.
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