Quantifying and Imaging Brain Phospholipid Metabolism In Vivo Using Radiolabeled Long Chain Fatty Acids

Phospholipids are major components of neuronal and glial membranes and participate in membrane remodeling and signal transduction (Axelrod, Burch, & Jelsema, 1988; Fisher & Agranoff, 1987; Porcellati, Goracci, & Arienti, 1983; Stephenson et al., 1994). Many of their functions involve the release of the essential polyunsaturated fatty acids (FAs), arachidonate (20:4n-6) and docosahexaenoate (22:6n-3) in signaling processes.Docosahexaenoate can modulate membrane fluidity and neuronal recovery following injury and participate in signal transduction and synaptic plasticity, whereas arachidonate and its bioactive metabolites (eicosanoids, leukotrienes, and monohydroxyeicosatetraenoic acids) are important second messengers (Axelrod, 1995; Horrocks and Yeo, 1999; Wolfe and Horrocks, 1994). However, in pathological conditions, such as inflammation, ischemia, and trauma, large quantities of FAs are liberated from phospholipids and contribute to cell dysfunction or death (Bazân & Rodriguez de Turco, 1980; Rabin et al., 1997). Abnormal brain phospholipid metabolism also occurs in essential FA deficiency (Bourre et al., 1989; Contreras et al., 1999b), Alzheimer disease (Farooqui, Rapoport, & Horrocks, 1997a; Ginsberg, Rafique, Xuereb, Rapoport, & Gershfeld, 1995; Pettegrew, Moossy, Withers, McKeag, & Panchalingam, 1988), chronic alcohol exposure (Pawlosky & Salem Jr., 1995), and possibly in human depression and bipolar disorder (Hibbeln, 1998; Stoll et al., 1999).