Modulation of microglial prostaglandin production by norepinephrine

Resident microglial cells can change their morphology and aquire an activated phenotype including enlargement of the perinuclear soma and the expression of new cell surface molecules and cytokines. Prostaglandins, superoxide radicals and nitric oxide are produced and released. Furthermore activated microglia has a high potential for phagocytosis of extracellular protein deposits or dying cells. Activation of microglial cells has been described in Alzheimer Dementia and both, a detrimental role (neurotoxic effects of radicals) and a beneficial role (phagozytosis of amyloid in the presence of anti-amiloid-antibodies) has been suggested. Microglial activation has also been found in a subgroup of schizophrenic patients and in late-onset depression. In-vivo studies showed a modulatory effect of locus coeruleus neurons on cortical microglia activation. Using cultivated primary microglial cells we could show that norepinephrine modulates microglial prostaglandin synthesis via beta-adrenergic receptors. We could further demonstrate that in-vivo microglial activation is accompanied by an upregulation of prostaglandin receptors. Therefore these findings suggest that modulation of the beta-adrenergic neurotransmission might not only influence neurotransmission but although microglial prostaglandin production. Furthermore, the effects of prostaglandins on microglial cells may depend on prostaglandin receptor expression, which varies between resting and activated cells.