Brain arachidonic acid cascade enzymes are upregulated in a rat model of unilateral parkinson disease

Abstract

Arachidonic acid (AA) signaling is upregulated in the caudate-putamen and frontal cortex of unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, a model for asymmetrical Parkinson disease. AA signaling can be coupled to D 2-like receptor initiated AA hydrolysis from phospholipids by cytosolic phospholipase A2 (cPLA2) and subsequent metabolism by cyclooxygenase (COX)-2. In unilaterally 6-OHDA- and sham-lesioned rats, we measured brain expression of cPLA2, other PLA2 enzymes, and COX-2. Activity and protein levels of cPLA2 were significantly higher as was COX-2-protein in caudate-putamen, frontal cortex and remaining brain on the lesioned compared to intact side of the 6-OHDA lesioned rats, and compared to sham brain. Secretory sPLA2 and Ca 2+- independent iPLA2 expression did not differ between sides or groups. Thus, the tonically increased ipsilateral AA signal in the lesioned rat corresponds to upregulated cPLA2 and COX-2 expression within the AA metabolic cascade, which may contribute to symptoms and pathology in Parkinson disease. © Springer Science+Business Media, LLC 2009.