Glucocorticoid-regulated crosstalk between arachidonic acid and endocannabinoid biochemical pathways coordinates cognitive-, neuroimmune-, and energy homeostasis-related adaptations to stress.
Arachidonic acid and its derivatives constitute the major group of signaling molecules involved in the innate immune response and its communication with all cellular and systemic aspects involved on homeostasis maintenance. Glucocorticoids spread throughout the organism their influences over key enzymatic steps of the arachidonic acid biochemical pathways, leading, in the central nervous system, to a shift favoring the synthesis of anti-inflammatory endocannabinoids over proinflammatory metabolites, such as prostaglandins. This shift modifies local immune-inflammatory response and neuronal activity to ultimately coordinate cognitive, behavioral, neuroendocrine, neuroimmune, physiological, and metabolic adjustments to basal and stress conditions. In the hypothalamus, a reciprocal feedback between glucocorticoids and arachidonate-containing molecules provides a mechanism for homeostatic control. This neurochemical switch is susceptible to fine-tuning by neuropeptides, cytokines, and hormones, such as leptin and interleukin-1beta, assuring functional integration between energy homeostasis control and the immune/stress response.
Malcher-Lopes
Renato
R
Laboratory of Mass Spectrometry, EMBRAPA-Center for Genetic Resources and Biotechnology, Brasília-DF, Brazil.
Buzzi
Marcelo
M
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis / Q000378:metabolism*; D003071:Cognition / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D063388:Endocannabinoids; D004734:Energy Metabolism / Q000502:physiology; D005938:Glucocorticoids / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007858:Learning; D015213:Neuroimmunomodulation / Q000502:physiology; D009473:Neuronal Plasticity; D018696:Neuroprotective Agents; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005938:Glucocorticoids; D018696:Neuroprotective Agents; D064801:Phospholipase A2 Inhibitors; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; D054467:Phospholipases A2