Thalamic Proteome Changes and Behavioral Impairments in Thiamine-deficient Rats

•Thiamine deficiency (TD) causes spatial cognitive deficit that is reversible by repeated trials to solve the maze.•More than one hundred thalamic proteins can be deregulated by a severe TD episode.•TD induces down or up regulation of enzymes not directly dependent on thiamine as a cofactor.•The alt...

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Published in:Neuroscience 2018-08, Vol.385, p.181-197
Main Authors: Nunes, Polliana Toledo, Gómez-Mendoza, Diana Paola, Rezende, Cristiana Perdigão, Figueiredo, Henrique César Pereira, Ribeiro, Angela Maria
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal - physiology
Body Weight - physiology
Cognition - physiology
Eating - physiology
Male
neurodegeneration
neuroproteome
Proteome
Proteomics
Rats
Rats, Wistar
spatial learning
Spatial Learning - physiology
thalamus
Thalamus - metabolism
Thiamine - metabolism
thiamine deficiency
Thiamine Deficiency - metabolism
Wistar rats
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Summary:•Thiamine deficiency (TD) causes spatial cognitive deficit that is reversible by repeated trials to solve the maze.•More than one hundred thalamic proteins can be deregulated by a severe TD episode.•TD induces down or up regulation of enzymes not directly dependent on thiamine as a cofactor.•The altered levels of β-tubulin, GFAP and vimentin might be the result of a compensatory repair effect due to TD insult. Thiamine deficiency (TD) has been used as an experimental model in rodents to study the molecular mechanisms of neurodegeneration and its association with behavioral changes. The aims of the present study were to investigate the spatial cognitive performance of pyrithiamine-induced thiamine deficiency (PTD) in adult male rats and disclose the thalamic proteome alterations caused by a severe TD episode. After the onset of the neurological signs, such as seizure and/or loss of righting reflex, the TD treatment was interrupted. Following 15 days of recovery, all rats were submitted to the spatial cognitive tasks in the Morris Water Maze (MWM). The results show that the PTD rats exhibited deficits during the learning process, which was reverted by repeated training. However, despite the spatial cognitive recovery, some protein changes were not reversible. The proteomic analysis, using label-free quantification, revealed deregulation of 183 thalamic proteins. Using bioinformatic tools, these proteins were categorized according to Gene Ontology functional annotation and metabolic pathways. We show that a severe TD affects proteins involved in different biological processes, such as, oxidative stress, neurotransmitter synthesis and synaptic vesicle cycle. These could explain the outcome in neurotransmitter release changes caused by TD, previously observed by our group and by other authors. These findings disclose the role of key proteins and metabolic pathways probably involved in the neurodegeneration process induced by TD. These proteins represent relevant molecular targets for future studies focusing also on the molecular basis of selective vulnerability of some brain areas to TD insult.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2018.06.003