Essential Fatty Acid Interactions - The Arachidonic Acid Cascade in The Central Nervous System (CNS)

The Arachidonic Acid Cascade in The Central Nervous System (CNS)

The arachidonic acid cascade is arguably the most elaborate signaling system neurobiologists have to deal with.

Daniele Piomelli Arachidonic Acid

The arachidonic acid cascade proceeds somewhat differently in the brain. Neurohormones, neuromodulators or neurotransmitters act as first messengers. They activate phospholipidase to release AA from neuron cell membranes as a free fatty acid. During its short lifespan, free AA may affect the activity of the neuron's ion channels and protein kinases. Or it may be metabolized to form eicosanoids, epoxyeicosatrienoic acids (EETs), neuroprotectin D or various endocannabinoids (anandamide and its analogs.)

The actions of eicosanoids within the brain are not as well characterized as they are in inflammation. It is theorized that they act within the neuron as second messengers controlling presynaptic inhibition and the activation of protein kinase C. They also act as paracrine mediators, acting across synapses to nearby cells. Although detail on the effects of these signals is scant, (Piomelli, 2000) comments

Neurons in the CNS are organized as interconnected groups of functionally related cells (e.g., in sensory systems). A diffusible factor released from a neuron into the interstitial fluid, and able to interact with membrane receptors on adjacent cells, would be ideally used to "synchronize" the activity of an ensemble of interconnected neural cells. Furthermore, during development and in certain forms of learning, postsynaptic cells may secrete regulatory factors which diffuse back to the presynaptic component, determining its survival as an active terminal, the amplitude of its sprouting, and its efficacy in secreting neurotransmitters—a phenomenon known as retrograde regulation. The participation of arachidonic acid metabolites in retrograde signaling and in other forms of local modulation of neuronal activity has been proposed.

Table (2) The arachidonic acid cascades act differently between the inflammatory response and the brain.
Arachidonic Acid Cascade
In inflammation In the brain
Major effect on Inflammation in tissue Neuronal excitability
AA released from White blood cells Neurons
Triggers for AA release Inflammatory stimuli Neurotransmitters, neurohormones
and neuromodulators
Intracellular effects on DNA transcription of cytokines and other
mediators of inflammation		 Activity of ion channels and protein
kinases
Metabolized to form Eicosanoids, resolvins, isofurans, isoprostanes,
lipoxins, epoxyeicosatrienoic acids (EETs)		 Eicosanoids, neuroprotectin D, EETs
and some endocannabinoids

The EPA and DGLA cascades are also present in the brain and their eicosanoid metabolites have been detected. The ways in which these differently affect mental and neural processes are not nearly as well characterized as are the effects in inflammation.

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