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Microglia Play a Role in Ethanol‐Induced Oxidative Stress and Apoptosis in Developing Hypothalamic Neurons
Author(s) -
Boyadjieva Nadka I.,
Sarkar Dipak K.
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01889.x
Subject(s) - oxidative stress , microglia , apoptosis , superoxide dismutase , reactive oxygen species , glutathione , programmed cell death , glutathione peroxidase , population , biology , catalase , chemistry , microbiology and biotechnology , endocrinology , biochemistry , medicine , inflammation , immunology , enzyme , environmental health
Background Animals exposed to alcohol during the developmental period develop many physiological and behavioral problems because of neuronal loss in various brain areas including the hypothalamus. Because alcohol exposure is known to induce oxidative stress in developing neurons, we tested whether hypothalamic cells from the fetal brain exposed to ethanol ( E t OH ) may alter the cell–cell communication between neurons and microglia, thereby leading to increased oxidative stress and the activation of apoptotic processes in the neuronal population in the hypothalamus. Methods Using enriched neuronal and microglial cells from fetal rat hypothalami, we measured cellular levels of various oxidants (O 2−, reactive oxygen species, nitrite), antioxidants (glutathione [ GSH ]), antioxidative enzymes (glutathione peroxidase [ GSH ‐ P x], catalase, superoxide dismutase) and apoptotic death in neurons in the presence and absence of E t OH or E t OH ‐treated microglial culture medium. Additionally, we tested the effectiveness of antioxidative agents in preventing E t OH or E t OH ‐treated microglial conditioned medium actions on oxidative stress and apoptosis in neuronal cell cultures. Results Neuronal cell cultures showed increased oxidative stress, as demonstrated by higher cellular levels of oxidants but lower levels of antioxidant and antioxidative enzymes, as well as, increased apoptotic death following treatment with E t OH . These effects of E t OH on oxidative stress and cell death were enhanced by the presence of microglia. Antioxidative agents protected developing hypothalamic neurons from oxidative stress and cellular apoptosis which is caused by E t OH or E t OH ‐treated microglial culture medium. Conclusions These data suggest that exposure of developing hypothalamic neurons to E t OH increases cellular apoptosis via the effects on oxidative stress of neurons directly and via increasing production of microglial‐derived factor(s).