Brain arachidonic acid uptake and turnover: implications for signaling and bipolar disorder

Abstract

Arachidonic acid was first detected in the brain in 1922. Although earlier work examined the role of arachidonic acid in growth and development, more recent advancements have elucidated roles for arachidonic acid in brain health and disease. In this review, we summarize evidence demonstrating that unesterified arachidonic acid in the plasma pool, which is supplied in part from adipose, is readily taken up and incorporated into brain phospholipids. By labeling plasma unesterified arachidonic acid, it is possible to trace the subsequent release of arachidonic acid from brain phospholipids upon neuroreceptor-mediated release by phospholipase A2 in response to drugs and neuroinflammation in rodents. With the synthesis of 11C labeled fatty acids, brain arachidonic acid signaling can now be measured in humans with position emission tomography. Arachidonic acid signals are known to regulate important biological functions, including neuroinflammation and excitotoxicity, and we focus on how the brain arachidonic acid cascade is a common target of drugs used to treat bipolar disorder (e.g. lithium, carbamazepine and valproate). A better understanding of the regulation of arachidonic acid uptake into the brain and the brain arachidonic acid cascade could lead to new imaging techniques and the identification of novel therapeutic targets in excitotoxicity, neuroinflammation and bipolar disorder.