DISTRIBUTION OF CYTOPLASMIC PHOSPHOLIPASE A2 (CPLA2) IN THE NORMAL RAT BRAIN AND AFTER NEURONAL INJURY INDUCED BY KAINATE

Abstract

Cytoplasmic phospholipase A2 (cPLA2) produces arachidonic acid from membrane phospholipids, and arachidonic acid which is generated by action of cPLA2 can be converted to several different classes of potent biological effectors, collectively called eicosanoids, by the enzyme cyclooxygenase (COX). The present study provides data on the distribution of cPLA2 in the normal rat brain, and cPLA2 and the inducible form of cyclooxygenase, cyclooxygenase-2 (COX-2) in the hippocampus after kainate lesions. Immunocytochemistry of the normal rat brain using a monoclonal mouse antibody to cPLA2 showed that the forebrain and midbrain were very lightly stained, except for the arcuate nucleus and the mammillary and supramammillary nuclei. The hindbrain, in contrast, contained many densely labelled neurons in the superior olivary and periolivary nuclei, the facial motor nucleus and the dorsal and ventral cochlear nuclei, Purkinje neurons in the cerebellum, neurons in the deep cerebellar nuclei, and the external cuneate nucleus. Electron microscopy of these areas showed that the enzyme was located in dendrites postsynaptic to unlabelled axon terminals. The dense staining of cPLA2 in the initial portions of the ascending auditory pathway, and in the cerebellum and nuclei connected to the cerebellum suggests that cPLA2 could play an important functional role in these regions. Systemic administration of kainate (10 mg/ml) to adult Wistar rats produces seizures and neurodegeneration. The effects of kainate administration on cPLA2 and COX-2 immunoreactivities were studied at 3 days and 1, 2, 4 and 11 weeks postinjection. cPLA2 immunoreactivity was increased in degenerating hippocampal neurons at 1 and 3 days after kainate injection, suggesting that PLA2 is involved in the mechanism of eel 1 death in these neurons. . In addition to neurons, cPLA2 and COX-2immunoreactivities were also observed in reactive astrocytes at 1, 2, 4 and 11 weeks after kainate injection. The high concentrations of cPLA2 and COX-2 in reactive astrocytes suggest that these cells could be important sources of eicosanoids. It is postulated that eicosanoids produced by reactive astrocytes could play an important role in propagation of neuronal injury, at the edge of glial scars.