Ethanol Stimulation of Microglia Release Increases ERK1/2-Dependent Neuronal cPLA2 Activity in Immature Cultured Cortical Preparations

Ethanol consumption typically begins during adolescence and is associated with age-dependent responses and maladaptive neuronal consequences. Our previous work established the role of a putative signaling cascade involving cytoplasmic phospholipase A 2 (cPLA 2 ), arachidonic acid (AA) and novel prot...

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Bibliographic Details
Published inNeurochemical research Vol. 45; no. 7; pp. 1592 - 1601
Main Authors Santerre-Anderson, J. L., Werner, D. F.
Format Journal Article
LanguageEnglish
Published New York Springer US 01.07.2020
Springer Nature B.V
Subjects
Adolescents
Age
Arachidonic acid
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Ethanol
Extracellular signal-regulated kinase
Glial cells
Isoforms
Kinases
MAP kinase
Microglia
Neurochemistry
Neurology
Neuronal-glial interactions
Neurosciences
Original Paper
Phospholipase
Phospholipase A2
Phosphorylation
Protein kinase C
Serine
Signaling
P38 MAPK
ERK1/2
Ethanol
Arachidonic acid
Cytoplasmic phospholipase A
Microglia
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Summary:Ethanol consumption typically begins during adolescence and is associated with age-dependent responses and maladaptive neuronal consequences. Our previous work established the role of a putative signaling cascade involving cytoplasmic phospholipase A 2 (cPLA 2 ), arachidonic acid (AA) and novel protein kinase C isoforms in adolescent hypnotic sensitivity. The current study aimed to further delineate this pathway by ascertaining the cellular specificity as well as the upstream activators of cPLA 2 using an immature cultured cortical preparation. A threefold increase in cPLA 2 was detected within 2 min of 100 mM ethanol exposure as measured by phosphorylation of serine 505 (Ser505). Increases in cPLA 2 activity were further observed to be primarily confined to neuronal cells. Increases in the number of neurons co-expressing cPLA2 Ser505 phosphorylation were prevented by preincubation with an ERK1/2 inhibitor, but not P38 MAPK inhibition. Finally, conditioned media studies were used to determine whether glial cells were involved in the ethanol-induced neuronal cPLA 2 activity. Rapid increases in neuronal cPLA2 activity appears to be initiated through ethanol stimulated microglial, but not astrocytic releasable factors. Taken together, these data extend the proposed signaling cascade involved in developmental ethanol responding
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-020-03024-z