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Focal thalamic degeneration from ethanol and thiamine deficiency is associated with neuroimmune gene induction, microglial activation, and lack of monocarboxylic acid transporters.

Qin L, Crews FT - Alcohol. Clin. Exp. Res. (2013)

Bottom Line: Wernicke's encephalopathy-Korsakoff syndrome (WE-KS) is common in alcoholics, caused by thiamine deficiency (TD; vitamin B1) and associated with lesions to the thalamus (THAL).Combined EtOH-TD treatment for 5 days (EtOH-TD5) showed activated microglia, proinflammatory gene induction and THAL neurodegeneration that was greater than that found with TD alone (TD5), whereas 10 days resulted in marked THAL degeneration and microglial-neuroimmune activation in both groups.The findings support the hypothesis that TD deficiency inhibits global glucose metabolism and that a reduced ability to process acetate for cellular energy results in THAL focal degeneration in alcoholics contributing to the high incidence of Wernicke-Korsakoff syndrome in alcoholism.

View Article: PubMed Central - PubMed

Affiliation: Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

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Related in: MedlinePlus

EtOH-thiamine deficiency (TD) induces astroglial activation in thalamus (THAL), but not in entorhinal cortex (ENT). C57BL/6 mice were treated with vehicle and EtOH+TD10 as described in Materials and Methods. Animals were sacrificed 24 hours following the last dose of EtOH treatment (5 g/kg, i.g. daily for 10 days). Brain sections were immunostained with glial fibrillary acidic protein (GFAP) astrocyte antibody. Astroglia (GFAP+IR) were in resting morphology in ENT of mice treated with both vehicle and EtOH+TD10. However, EtOH+TD10-treated THAL showed significant astroglial activation showed by enlarged GFAP+IR cells and intensified GFAP staining, compared with vehicle controls. Astroglia in TD alone treatment showed activated morphology in ENT, compared with EtOH+TD10-treated ENT. Scale bar = 50 μm.
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fig07: EtOH-thiamine deficiency (TD) induces astroglial activation in thalamus (THAL), but not in entorhinal cortex (ENT). C57BL/6 mice were treated with vehicle and EtOH+TD10 as described in Materials and Methods. Animals were sacrificed 24 hours following the last dose of EtOH treatment (5 g/kg, i.g. daily for 10 days). Brain sections were immunostained with glial fibrillary acidic protein (GFAP) astrocyte antibody. Astroglia (GFAP+IR) were in resting morphology in ENT of mice treated with both vehicle and EtOH+TD10. However, EtOH+TD10-treated THAL showed significant astroglial activation showed by enlarged GFAP+IR cells and intensified GFAP staining, compared with vehicle controls. Astroglia in TD alone treatment showed activated morphology in ENT, compared with EtOH+TD10-treated ENT. Scale bar = 50 μm.

Mentions: To investigate the response of astrocytes to TD, we compared THAL and ENT using astrocyte markers glial fibrillary acidic protein (GFAP) (Fig. 7), glutamine synthetase (GS) (Fig. 8), and the excitatory amino acid transporter (EAAT1) (Fig. 9). In general, ENT astrocyte marker protein expression, for example, GFAP+IR, GS+IR, and EAAT1 + IR appears more robust than that found in THAL. EtOH-TD10 induced a loss of THAL astrocytes markers, consistent with TD-induced focal THAL degeneration involving toxicity to both neurons and astrocytes. Interestingly, astrocyte GFAP shows darker staining in TD10, in both THAL and ENT, but not in EtOH-TD10. In THAL, EtOH-TD10 has a few dark stained cells but a general loss, whereas in ENT, EtOH-TD10 shows GAFP + IR cell morphology more like controls than TD10 (Fig. 7). Quantification of GFAP + IR cells/mm2 morphological activation finds 59 ± 6% activated in TD, 17 ± 2% activated in EtOH + TD (p < 0.01 vs. TD alone; controls 2 ± 0.4; p < 0.01 vs. TD and EtOH + TD) consistent with EtOH reducing the TD astrocyte insult in ENT that contrasts with EtOH increasing microglial activation in THAL.


Focal thalamic degeneration from ethanol and thiamine deficiency is associated with neuroimmune gene induction, microglial activation, and lack of monocarboxylic acid transporters.

Qin L, Crews FT - Alcohol. Clin. Exp. Res. (2013)

EtOH-thiamine deficiency (TD) induces astroglial activation in thalamus (THAL), but not in entorhinal cortex (ENT). C57BL/6 mice were treated with vehicle and EtOH+TD10 as described in Materials and Methods. Animals were sacrificed 24 hours following the last dose of EtOH treatment (5 g/kg, i.g. daily for 10 days). Brain sections were immunostained with glial fibrillary acidic protein (GFAP) astrocyte antibody. Astroglia (GFAP+IR) were in resting morphology in ENT of mice treated with both vehicle and EtOH+TD10. However, EtOH+TD10-treated THAL showed significant astroglial activation showed by enlarged GFAP+IR cells and intensified GFAP staining, compared with vehicle controls. Astroglia in TD alone treatment showed activated morphology in ENT, compared with EtOH+TD10-treated ENT. Scale bar = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3959259&req=5

fig07: EtOH-thiamine deficiency (TD) induces astroglial activation in thalamus (THAL), but not in entorhinal cortex (ENT). C57BL/6 mice were treated with vehicle and EtOH+TD10 as described in Materials and Methods. Animals were sacrificed 24 hours following the last dose of EtOH treatment (5 g/kg, i.g. daily for 10 days). Brain sections were immunostained with glial fibrillary acidic protein (GFAP) astrocyte antibody. Astroglia (GFAP+IR) were in resting morphology in ENT of mice treated with both vehicle and EtOH+TD10. However, EtOH+TD10-treated THAL showed significant astroglial activation showed by enlarged GFAP+IR cells and intensified GFAP staining, compared with vehicle controls. Astroglia in TD alone treatment showed activated morphology in ENT, compared with EtOH+TD10-treated ENT. Scale bar = 50 μm.
Mentions: To investigate the response of astrocytes to TD, we compared THAL and ENT using astrocyte markers glial fibrillary acidic protein (GFAP) (Fig. 7), glutamine synthetase (GS) (Fig. 8), and the excitatory amino acid transporter (EAAT1) (Fig. 9). In general, ENT astrocyte marker protein expression, for example, GFAP+IR, GS+IR, and EAAT1 + IR appears more robust than that found in THAL. EtOH-TD10 induced a loss of THAL astrocytes markers, consistent with TD-induced focal THAL degeneration involving toxicity to both neurons and astrocytes. Interestingly, astrocyte GFAP shows darker staining in TD10, in both THAL and ENT, but not in EtOH-TD10. In THAL, EtOH-TD10 has a few dark stained cells but a general loss, whereas in ENT, EtOH-TD10 shows GAFP + IR cell morphology more like controls than TD10 (Fig. 7). Quantification of GFAP + IR cells/mm2 morphological activation finds 59 ± 6% activated in TD, 17 ± 2% activated in EtOH + TD (p < 0.01 vs. TD alone; controls 2 ± 0.4; p < 0.01 vs. TD and EtOH + TD) consistent with EtOH reducing the TD astrocyte insult in ENT that contrasts with EtOH increasing microglial activation in THAL.

Bottom Line: Wernicke's encephalopathy-Korsakoff syndrome (WE-KS) is common in alcoholics, caused by thiamine deficiency (TD; vitamin B1) and associated with lesions to the thalamus (THAL).Combined EtOH-TD treatment for 5 days (EtOH-TD5) showed activated microglia, proinflammatory gene induction and THAL neurodegeneration that was greater than that found with TD alone (TD5), whereas 10 days resulted in marked THAL degeneration and microglial-neuroimmune activation in both groups.The findings support the hypothesis that TD deficiency inhibits global glucose metabolism and that a reduced ability to process acetate for cellular energy results in THAL focal degeneration in alcoholics contributing to the high incidence of Wernicke-Korsakoff syndrome in alcoholism.

View Article: PubMed Central - PubMed

Affiliation: Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Show MeSH
Related in: MedlinePlus