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Publication : TLR4-dependent metabolic changes are associated with cognitive impairment in an animal model of type 1 diabetes.

First Author  Kawamoto EM Year  2014
Journal  Biochem Biophys Res Commun Volume  443
Issue  2 Pages  731-7
PubMed ID  24342620 Mgi Jnum  J:211853
Mgi Id  MGI:5576810 Doi  10.1016/j.bbrc.2013.12.039
Citation  Kawamoto EM, et al. (2014) TLR4-dependent metabolic changes are associated with cognitive impairment in an animal model of type 1 diabetes. Biochem Biophys Res Commun 443(2):731-7
abstractText  We investigated the role of Toll-like receptor 4 (TLR4), a major mediator of innate immune responses, on cognitive performance in a type 1 diabetes model (T1D). After administration of streptozotocin, both TLR4 knockout (TLR4 KO) and wild type (WT) diabetic mice displayed metabolic alterations similar to those observed in T1D patients, including increased levels of glucose, cholesterol, triglycerides and ketones. T1D mice exhibited cognitive impairment which was less severe in TLR4 KO mice compared to WT mice. WT mice with higher glucose and those with higher triglyceride levels exhibited significantly more anxiety and impaired memory compared to those with lower levels of glucose and triglycerides; these correlations were absent in TLR4 KO mice. Additional findings suggest roles for TLR4 signaling in modifying the expression of enzymes involved in energy metabolism in brain cells in the setting of T1D. Our data show that TLR4 contributes to the negative impact of T1D on anxiety and cognition.
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