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Cytosolic phospholipase A 2 is induced in reactive glia following different forms of neurodegeneration
Author(s) -
Stephenson Diane,
Rash Karen,
Smalstig Barry,
Roberts Edda,
Johnstone Edward,
Sharp John,
Panetta Jill,
Little Sheila,
Kramer Ruth,
Clemens James
Publication year - 1999
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199908)27:2<110::aid-glia2>3.0.co;2-c
Subject(s) - biology , phospholipase a2 , phospholipase , cytosol , neurodegeneration , microbiology and biotechnology , biochemistry , medicine , disease , enzyme
Many recent studies have emphasized the deleterious role of inflammation in CNS injury. Increases in free fatty acids, eicosanoids, and products of lipid peroxidation are known to occur in various conditions of acute and chronic CNS injury, including cerebral ischemia, traumatic brain injury, and Alzheimer's disease. Although an inflammatory response can be induced by many different means, phospholipases, such as cytosolic phospholipase A 2 (cPLA 2 ), may play an important role in the production of inflammatory mediators and in the production of other potential second messengers. cPLA 2 hydrolyzes membrane phospholipids and its activity liberates free fatty acids leading directly to the production of eicosanoids. We investigated the cellular localization of cytosolic phospholipase A 2 in the CNS following: (1) focal and global cerebral ischemia, (2) facial nerve axotomy, (3) human cases of Alzheimer's disease, (4) transgenic mice overexpressing mutant superoxide dismutase, a mouse model of amyotrophic lateral sclerosis, and (5) transgenic mice overexpressing mutant amyloid precursor protein, which exhibits age‐related amyloid deposition characteristic of Alzheimer's disease. We show that in every condition evaluated, cytosolic phospholipase A 2 is present in reactive glial cells within the precise region of neuron loss. In conditions where neurons did not degenerate or are protected from death, cytosolic phospholipase A 2 is not observed. Both astrocytes and microglial cells are immunoreactive for cytosolic phospholipase A 2 following injury, with astrocytes being the most consistent cell type expressing cytosolic phospholipase A 2 . The presence of cytosolic phospholipase A 2 does not merely overlap with reactive astroglia, as reactive astrocytes were observed that did not exhibit cytosolic phospholipase A 2 immunoreactivity. In most conditions evaluated, inflammatory processes have been postulated to play a pivotal role and may even participate in neuronal cell death. These results suggest that cytosolic phospholipase A 2 may prove an attractive therapeutic target for neurodegeneration. GLIA 27:110–128, 1999. © 1999 Wiley‐Liss, Inc.