Acute Liver Toxicity Modifies Protein Expression of Glutamate Transporters in Liver and Cerebellar Tissue

Abstract

Glutamate is the main excitatory amino acid acting at the level of pre and postsynaptic neurons, as well as in glial cells. It is involved in the coordinated modulation of energy metabolism, glutamine synthesis, and ammonia detoxification. The relationship between the functional status of liver and brain has been known for many years. The most widely recognized aspect of this relation is the brain dysfunction caused by acute liver injury that manifests a wide spectrum of neurologic and psychiatric abnormalities. Inflammation, circulating neurotoxins, and impaired neurotransmission have been reported in this pathophysiology. In the present contribution, we report the effect of a hepatotoxic compound like CCl4 on the expression of key proteins involved in glutamate uptake and metabolism as glutamate transporters and glutamine synthetase in mice liver, brain, and cerebellum. Our findings highlight a differential expression pattern of glutamate transporters in cerebellum. A significant Purkinje cells loss, in parallel to an up-regulation of glutamine synthetase, and astrogliosis in the brain have also been noticed. In the intoxicated liver, glutamate transporter 1 expression is up-regulated, in contrast to glutamine synthetase which is reduced in a time-dependent manner. Taken together our results demonstrate that the exposure to an acute CCl4 insult, leads to the disruption of glutamate transporters expression in the liver-brain axis and therefore a severe alteration in glutamate-mediated neurotransmission might be present in the central nervous system.

Generalizability, Robustness and Replicability When Evaluating Wellbeing of Laboratory Mice with Various Methods

“…This suggests that nesting activity is either the most sensitive method to detect distress or CCl 4 causes a specific change in nesting behavior independent of inducing distress. Consistent with the second hypothesis is the observation that CCl 4 can change protein expression, reduce the number of neurons in the brain [ 46 ] and can also lead to brain damage [ 47 ]. Such changes in the central nervous system could influence complex behavior such as nesting activity.…”

New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets

“… 71 Studies on animal models of HE and hyperammonemic condition indicated that the protein expression of EAAT2 significantly decreased in the brain which led to an increase in the concentration of extracellular glutamate and progression of cerebral edema. 72 - 76 …”

Rutin attenuates d-galactose-induced oxidative stress in rats’ brain and liver: molecular docking and experimental approaches

“…The liver and the brain are the two most crucial organs, and ROS assault throughout ageing causes both of these organs to steadily deteriorate 4 . There is a relationship between the functional status of the liver and brain known as hepatic encephalopathy resulting from insufficiency of the liver to remove toxins from the blood leading to brain dysfunction 5 . Furthermore, exposure to ROS increases the incidence of several liver diseases throughout the life-span, including aging 6 .…”

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