Role of astrocytes in thiamine deficiency

Abstract

Thiamine deficiency (TD) is the underlying cause of Wernicke's encephalopathy (WE), an acute neurological disorder characterized by structural damage to key periventricular structures in the brain. Increasing evidence suggests these focal histological lesions may be representative of a gliopathy in which astrocyte-related changes are a major feature of the disorder. These changes include a loss of the glutamate transporters GLT-1 and GLAST concomitant with elevated interstitial glutamate levels, lowered brain pH associated with increased lactate production, decreased levels of GFAP, reduction in the levels of glutamine synthetase, swelling, alterations in levels of aquaporin-4, and disruption of the blood-brain barrier. This review focusses on how these manifestations contribute to the pathophysiology of TD and possibly WE.

Disruption of Intracellular ATP Generation and Tight Junction Protein Expression during the Course of Brain Edema Induced by Subacute Poisoning of 1,2-Dichloroethane

“…Nevertheless, intracellular contents of ATP and lactic acid are the important indicators of energy metabolism in the brain (Borutaite, 2010 ; Dienel, 2014 ). Though disordered energy metabolism is the main cause of cytotoxic edema in the brain, it might also result in vasogenic brain edema since increased levels of intracellular lactic acid induced by cytotoxic edema might disturb the function of the blood brain barrier (Chen et al, 2000 ; Rose, 2010 ; Yang et al, 2012 ; Afadlal et al, 2014 ). Therefore, although brain edema can be divided into cytotoxic and vasogenic edema at the initial stage, given that cytotoxic and vasogenic edema can be the cause of each other, it will become mixed brain edema soon.…”

Central Role of Maladapted Astrocytic Plasticity in Ischemic Brain Edema Formation

“…Along with morphological plasticity, astrocytes also possess functional plasticity in brain hydromineral homeostasis by changing the expression of ion transport molecules. The molecules that are involved in this astrocytic functional plasticity in the edema formation include GFAP (Abrahám et al, 2003 ), AQP4 (Wang and Hatton, 2009 ), Na + , K + , 2Cl − and water cotransporter (NKCC)1 (Hertz et al, 2014 ), sulfonylurea receptor 1-transient receptor potential melastatin4 channel (Karschin et al, 1998 ), sodium pump (Illarionova et al, 2010 ), glutamine synthetase (Wang et al, 2013b ), glutamate-aspartate transporter (Sullivan et al, 2007 ; Gottipati et al, 2015 ), and glutamate transporter-1 (GLT-1) (Afadlal et al, 2014 ; Mogoanta et al, 2014 ) in addition to those that are involved in GABA (Wang et al, 2013a ) and glutamate metabolism (Wang et al, 2013b ). Among these molecules, GFAP is the leading molecule that influences the spatial localization of other molecules.…”

Thiamine Deficiency and Neurodegeneration: the Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy

“…Decreased thiamine levels are correlated with the aging process [13]. The recommended daily allowance for thiamine in most countries is set at about 1.4 mg [14], while chronic alcohol consumption is the primary cause of TD in the United States and other developed countries [15, 16]. Evidence suggests that TD occurs in chronic alcoholics at a frequency of at least 25–31 % and up to 80 % [17].…”