Imaging plasma docosahexaenoic acid (dha) incorporation into the brain in vivo, as a biomarker of brain DHA: Metabolism and neurotransmission

Abstract

Docosahexaenoic acid (DHA) is critical for normal brain structure and function, and its brain concentration depends on dietary DHA content and hepatic conversion from its dietary derived n-3 precursor, a-linolenic acid (α-LNA). We developed an in vivo method in rats using quantitative autoradiography to image incorporation into brain of unesterified plasma DHA, and showed that the incorporation rate equals the rate of brain metabolic DHA consumption. Thus, quantitative imaging of DHA incorporation from plasma into brain can be used as a biomarker of brain DHA metabolism and neurotransmission. The method has been extended to humans with the use of positron emission tomography (PET). Furthermore, imaging in unanesthetized rats using DHA incorporation as a biomarker in response to N-methyl-D-aspartate (NMDA) administration confirms that regional DHA signaling is independent of extracellular calcium, and likely mediated by a calcium-independent phospholipase A2 (iPLA2). Studies in mice in which iPLA2-VIA (β) was knocked out confirmed that this enzyme is critical for baseline and muscarinic cholinergic signaling involving DHA.

Keywords

• docosahexaenoic acid
• iPLA2
• cPLA2
• brain
• biomarker
• imaging
• positron
• arachidonic
• calcium
• rat
• human
• PET