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Pyrithiamine-induced thiamine deficiency alters proliferation and neurogenesis in both neurogenic and vulnerable areas of the rat brain

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Abstract

Thiamine deficiency (TD) leads to Wernicke’s encephalopathy (WE), in which focal histological lesions occur in periventricular areas of the brain. Recently, impaired neurogenesis has been reported in the hippocampus during the dietary form of TD, and in pyrithiamine-induced TD (PTD), a well-characterized model of WE. To further characterize the consequences of PTD on neural stem/progenitor cell (NSPC) activity, we have examined the effect of this treatment in the rat on both the subventricular zone (SVZ) of the rostral lateral ventricle and subgranular layer (SGL) of the hippocampus, and in the thalamus and inferior colliculus, two vulnerable brain regions in this disorder. In both the SVZ and SGL, PTD led to a decrease in the numbers of bromodeoxyuridine-stained cells, indicating that proliferation of NSPCs destined for neurogenesis in these areas was reduced. Doublecortin (DCX) immunostaining in the SGL was decreased, indicating a reduction in neuroblast formation, consistent with impaired NSPC activity. DCX labeling was not apparent in focal areas of vulnerability. In the thalamus, proliferation of cells was absent while in the inferior colliculus, numerous actively dividing cells were apparent, indicative of a differential response between these two brain regions. Exposure of cultured neurospheres to PTD resulted in decreased proliferation of NSPCs, consistent with our in vivo findings. Together, these results indicate that PTD considerably affects cell proliferation and neurogenesis activity in both neurogenic areas and parts of the brain known to display structural and functional vulnerability, confirming and extending recent findings on the effects of TD on neurogenesis. Future use of NSPCs in vitro may allow a closer and more detailed examination of the mechanism(s) underlying inhibition of these cells during TD.

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Notes

  1. Nutritional information of the rodent diet: Crude protein: 18.9 %; Crude oil: 6.0 %; Carbohydrate: 57.33 %; Sugar: 4.93 %; Starch: 41.24 %; Vitamin A: 15.4 IU/g; Vitamin E: 101 mg/kg; Vitamin K (menadione): 51 mg/kg; Vitamin B1: <0.1 mg/kg; Vitamin B2: 14.9 mg/kg; Niacin: 41.2 mg/kg; Vitamin: B6 18.5 mg/kg; Pantothenic acid: 33 mg/kg; Biotin: 0.3 mg/kg; Folate: 3.34 mg/kg; Vitamin D3: 1.5 IU/g; Vitamin B12: 0.08 mg/kg.

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Acknowledgments

This study was funded by a grant from the Canadian Institutes of Health Research.

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Authors and Affiliations

  1. Department of Medicine, University of Montreal, Montreal, QC, Canada

    Alan S. Hazell, Dongmei Wang, Raluca Oanea, Simon Sun, Meghmik Aghourian & Jee Jung Yong

  2. NeuroRescue Laboratory, Hôpital Saint-Luc (CHUM), 1058 St-Denis, Montreal, QC, Canada, H2X 3J4

    Alan S. Hazell

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  1. Alan S. Hazell
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  2. Dongmei Wang
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  3. Raluca Oanea
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  4. Simon Sun
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Correspondence to Alan S. Hazell.

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Hazell, A.S., Wang, D., Oanea, R. et al. Pyrithiamine-induced thiamine deficiency alters proliferation and neurogenesis in both neurogenic and vulnerable areas of the rat brain. Metab Brain Dis 29, 145–152 (2014). https://doi.org/10.1007/s11011-013-9436-9

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  • DOI: https://doi.org/10.1007/s11011-013-9436-9

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