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Microglial AGE-albumin is critical in promoting alcohol-induced neurodegeneration in rats and humans.

ABSTRACT: Alcohol is a neurotoxic agent, since long-term heavy ingestion of alcohol can cause various neural diseases including fetal alcohol syndrome, cerebellar degeneracy and alcoholic dementia. However, the molecular mechanisms of alcohol-induced neurotoxicity are still poorly understood despite numerous studies. Thus, we hypothesized that activated microglial cells with elevated AGE-albumin levels play an important role in promoting alcohol-induced neurodegeneration. Our results revealed that microglial activation and neuronal damage were found in the hippocampus and entorhinal cortex following alcohol treatment in a rat model. Increased AGE-albumin synthesis and secretion were also observed in activated microglial cells after alcohol exposure. The expressed levels of receptor for AGE (RAGE)-positive neurons and RAGE-dependent neuronal death were markedly elevated by AGE-albumin through the mitogen activated protein kinase pathway. Treatment with soluble RAGE or AGE inhibitors significantly diminished neuronal damage in the animal model. Furthermore, the levels of activated microglial cells, AGE-albumin and neuronal loss were significantly elevated in human brains from alcoholic indivisuals compared to normal controls. Taken together, our data suggest that increased AGE-albumin from activated microglial cells induces neuronal death, and that efficient regulation of its synthesis and secretion is a therapeutic target for preventing alcohol-induced neurodegeneration.

SUBMITTER: Byun K

PROVIDER: S-EPMC4139297 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Microglial AGE-albumin is critical in promoting alcohol-induced neurodegeneration in rats and humans.

Byun Kyunghee K Bayarsaikhan Delger D Bayarsaikhan Enkhjargal E Son Myeongjoo M Oh Seyeon S Lee Jaesuk J Son Hye-In HI Won Moo-Ho MH Kim Seung U SU Song Byoung-Joon BJ Lee Bonghee B

PloS one 20140820 8

Alcohol is a neurotoxic agent, since long-term heavy ingestion of alcohol can cause various neural diseases including fetal alcohol syndrome, cerebellar degeneracy and alcoholic dementia. However, the molecular mechanisms of alcohol-induced neurotoxicity are still poorly understood despite numerous studies. Thus, we hypothesized that activated microglial cells with elevated AGE-albumin levels play an important role in promoting alcohol-induced neurodegeneration. Our results revealed that microgl ...[more]

PMID: 25140518

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Microglial AGE-albumin is critical in promoting alcohol-induced neurodegeneration in rats and humans.

Publications

Microglial AGE-albumin is critical in promoting alcohol-induced neurodegeneration in rats and humans.

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