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Sub‐neurodegenerative Levels of Binge Alcohol Reduce Calcium‐independent Phospholipase A2 (iPLA2) Levels in Rat Brain: An Unrecognized Initial Sign of Neuroinflammation
Author(s) -
Schreiber Jennifer Ann,
Tajuddin Nuzhath,
Kouzoukas Dimitrios,
Kim HeeYong,
Collins Michael
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.499.5
Subject(s) - neuroinflammation , neurodegeneration , endocrinology , medicine , arachidonic acid , docosahexaenoic acid , phospholipase a2 , oxidative stress , chemistry , binge drinking , biochemistry , alcohol , biology , inflammation , polyunsaturated fatty acid , enzyme , fatty acid , disease , alcohol consumption
Selective degeneration of dentate granule cells in hippocampus (HC), pyramidal cells in entorhinal cortex (EC), and olfactory bulb neurons occurs in adult male rats subjected to severe alcohol (ethanol) binges over 4 days that generate maximal blood alcohol levels of 350–450 mg/dl. Concurrent with brain damage specifically in these brain regions, significant alterations are elicited by alcohol in the levels of phospholipase A2 (PLA2) enzymes, i.e., (1) increases in Ca 2+ ‐dependent cytosolic cPLA2 and secreted sPLA2, two membrane phospholipid‐metabolizing enzymes causing neuroinflammation via mobilization of omega‐6 arachidonic acid, a largely pro‐oxidative neurocellular mediator; and (2) reductions in Ca 2+ ‐independent iPLA2, known to selectively regulate membrane release and turnover of anti‐inflammatory, anti‐oxidative omega‐3 docosahexaenoic acid (DHA). Furthermore, these neurodegenerative and neuroinflammatory changes are replicated in vitro , along with a loss in DHA content itself, in rat organotypic adult‐age HC‐EC slice cultures binge‐treated with 100 mM (~460 mg/dl) alcohol. Importantly, DHA pre‐supplementation of the slices prevents the neurodegeneration and PLA2 changes caused by alcohol (Tajuddin et al. 2014). The objective of this study was to determine if phospholipid‐mediated neuroinflammatory changes exist from alcohol in the absence of neurodegeneration. Here we report that rats subjected to less severe binges ‐ and thus lower blood alcohol levels of ~200 mg/dl, which are insufficient to cause detectable brain damage and/or neuroinflammatory cPLA2 and sPLA2 elevations ‐nevertheless cause significantly reduced iPLA2 levels that are largely reversed by DHA supplementation. The results imply that iPLA2 depletion and, we suspect, loss of cellular/membrane DHA (that iPLA2 regulates), are critical, previously unappreciated first indicators or markers of brain neuroinflammation due to binge alcohol. Similar changes in iPLA2, potentially due to its sensitivity, may have a bearing on other forms of brain insults causing neuroinflammation and ultimately neurodamage. Support or Funding Information Research support: NIH U01 AA018279 (MAC and HYK) and NIH T32 AA013527 (Loyola Medical Center Alcohol Research Program) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .