Phosphatidyl lipids and cleavage sites Phosphatidyl lipids and cleavage sites. Phosphoglycerides most times X is C=O.

Structure of simple sphingolipids. Membrane lipids, found in myelin.

Myelin around a spinal cord axon from dog.

Essential lipid in membranes, used to produce steroid hormones, vitamin D, bile acids. Produced in liver of all animals, not found in prokaryotes, limited in plants and fungi. Hydroxyl group interacts with polar head groups of sphingolipids while the hydrophobic bulky carbon chain is embedded in the membrane.

Highest levels in brain, then adrenal where it is used as a precursor for corticosteroids and aldosterone.

Cholesterol increases with age though synthesis decreases Cholesterol increases with age though synthesis decreases. Transport from liver. Very low turnover in brain relative to rest of body. Synthesis by astrocytes.

No movement between leaflets--thermodynamically inhibited No movement between leaflets--thermodynamically inhibited. May be proteins that catalyze flip flop. Movement is allowed within the same plane.

Cholesterol role in membrane stability Cholesterol role in membrane stability. Structural role, can inhibit Na permeability, participate in endocytosis, generate lipid rafts, high density signaling centers in neuronal processes.

Saturated fatty acids associated with p-choline and sphingomyelin P-ethanolamine, p-serine and p-inositols have both saturated and unsaturated fatty acids. Axons >>cholesterol than synaptic membranes.

Lipid raft anchored by spectrin and ankrin to cytoskeleton Lipid raft anchored by spectrin and ankrin to cytoskeleton. Rafts are small and transient. Cholesterol dependent. Proteins: receptors, kinases, phosphatases, anchoring proteins, scaffold proteins, etc. Cholesterol can promote GPCR dimerization which reduces ligand binding.

Free fatty acids as signaling molecules cPLA2 translocation to membrane is stimulated by Ca2+, enzymatic activity is activated by MAPK phosphorylation--independent mechanisms of regulation.

PAF receptor antagonist reduces stroke volume and damage after middle cerebral artery occlusion.

PAF inhibitor protects cells infected with HIV as well PAF inhibitor protects cells infected with HIV as well. Implications for neuro-AIDS.

Endocannabinoids Anandamide is synthesized from phosphatidylcholine, 2-AG is synthesized from DAG by DAG lipase. Released, interact with CB1 receptor, uptaken by a transporter (blocked by AM404), broken down into AA or other. Some steps are Ca dependent, consistent with the “on-demand” generation of endocannabinoids.

CB1 receptor is Gi/Go linked, presynaptically inhibits transmitter release (GABA or glutamate usually). Release is typically retrograde. Necessary for many forms of plasticity including LTD at GABA synapses in HPC and amygdala, but also glutamate synapses in striatum and Nac. Role in memory and learning deficits associated with marijuana use?

To confirm that the doses of HU-210 and D9-THC utilized in the biochemical studies promote the tetrad of CB1 receptor-dependent behaviors, we next examined the acute effects of these agonists on locomotor activity, nociception, catalepsy and body temperature (Fig. 2). Marc Caron, Duke University 2011.

Dietary n-3 fatty acids were positively related to cognitive test scores in male and female children, while n-6 showed the reverse relationship, significantly so in females. In female children the positive effects of n-3 intake were twice as strong as in males and exceeded the negative effects of lead exposure. This suggests that increasing dietary intake of n-3 and decreasing n-6 fatty acids may have cognitive benefits in children, especially in females.

Omega 3 deficient diet prevents endocannabinoid-induced LTD in the prefrontal cortex.

n-3–deficient mice (n = 24) spent more time immobile (b) and less time swimming (b) than n-3 diet mice (n = 19). Imipramine (20 mg per kg, intraperitoneal) induced antidepressant-like effects in both groups: decreased immobility time (a) and increased time swimming (b). n-3 deficiency decreased the number of social exploration and increased the number of litter scratching, an index of anxiety. We tested the effect of WIN (a cannabinoid agonist) on emotional behavior, measured in the open-field test35, immediately after the injection (Fig. 5c,d). In n-3 mice, WIN (0.1 mg per kg) reduced the time spent in the center of the arena and increased thigmotaxis. This anxiogenic effect of WIN (0.1 mg per kg) was ablated in n-3–deficient mice, consistent with our biochemical and synaptic data showing impaired CB1R functionality in n-3 deficient mice.