Regulation of MCP-1 production in brain by stress and noradrenaline-modulating drugs

• Published in: Journal of neurochemistry Vol. 113; no. 2; pp. 543 - 551
• Main Authors: Madrigal, Jose L.M, Garcia-Bueno, Borja, Hinojosa, Ara E, Polak, Paul, Feinstein, Douglas L, Leza, Juan C
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.04.2010; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: Adrenergic beta-Antagonists - pharmacology; Adrenergic Uptake Inhibitors - pharmacology; Adult and adolescent clinical studies; Aldehyde-Lyases - pharmacology; Animals; Astrocytes - drug effects; Astrocytes - metabolism; Benserazide - pharmacology; Biochemistry and metabolism; Biological and medical sciences; Brain; Brain - drug effects; Brain - metabolism; Brain - pathology; CCL2; Central nervous system; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Corticosterone - blood; Depression; desipramine; Desipramine - pharmacology; Drug Administration Routes; Drug therapy; Enzyme Inhibitors - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Male; MCP-1; Medical sciences; Metyrapone - pharmacology; Mice; Mice, Inbred C57BL; Mood disorders; noradrenaline; norepinephrine; Norepinephrine - metabolism; Propranolol - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Wistar; Restraint, Physical - methods; RNA, Messenger - metabolism; Rodents; Stress; Stress, Physiological - physiology; Vertebrates: nervous system and sense organs; Modification; MCP-1; Rat; Corticosterone; Neuroglia; Central nervous system; Glucocorticoid; Precursor; desipramine; Encephalon; CCL2; noradrenaline; Propranolol; Mood disorder; Drug; Rodentia; Depression; Astrocyte; Stress; Vertebrata; Mammalia; Treatment; Mouse; Adrenal hormone; Adrenergic receptor; Monocyte chemoattractant protein 1
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2010.06623.x

J. Neurochem. (2010) 113, 543-551. While it is accepted that noradrenaline (NA) reduction in brain contributes to the progression of certain neurodegenerative diseases, the mechanisms through which NA exerts its protective actions are not well known. We previously reported that NA induced production of monocyte chemoattractant protein (MCP-1/CCL2) in cultured astrocytes mediated some of the neuroprotective actions of NA. We have now examined the regulation of MCP-1 production in vivo. Treatment of mice with the NA precursor l-threo-3,4-dihydroxyphenylserine induced the production of MCP-1 in astrocytes. In contrast, exposure to stress (a process known to elevate brain NA levels) produced only a moderate increase of MCP-1 because of the inhibitory activity of glucocorticoids released during the stress response. Similarly, corticosterone treatment of astrocytes caused a reduction of constitutive as well as the NA-induced MCP-1 production. When stressed rats had the production of glucocorticoids blocked by the selective inhibitor metyrapone, a large increase of MCP-1 concentration was observed in cortex, whereas propranolol (a beta adrenergic receptor blocker) avoided modifications of MCP-1 after stress. Desipramine (an inhibitor of NA reuptake) also caused an increase of MCP-1 in cortex. These data suggest that some phenomena caused by the alteration of NA or glucocorticoids could be mediated by MCP-1.