Serotonin transporter (SERT) and translocator protein (TSPO) expression in the obese ob/ob mouse

Springer Science and Business Media LLC - Tập 12 - Trang 1-8 - 2011
Gino Giannaccini1, Laura Betti1, Lionella Palego1, Andrea Pirone2, Lara Schmid1, Mario Lanza1, Laura Fabbrini1, Caterina Pelosini3, Margherita Maffei3, Ferruccio Santini3, Aldo Pinchera3, Antonio Lucacchini1
1Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, University of Pisa,, Pisa, Italy
2Department of Physiological Sciences, University of Pisa, Pisa, Italy
3Department of Endocrinology and Kidney, University Hospital of Pisa, Pisa, Italy

Tóm tắt

An ever growing body of evidences is emerging concerning metabolism hormones, neurotransmitters or stress-related biomarkers as effective modulators of eating behavior and body weight in mammals. The present study sought at examining the density and affinity of two proteins related to neurotransmission and cell metabolism, the serotonin transporter SERT and the cholesterol import-benzodiazepine site TSPO (translocator protein), in a rodent leptin-lacking mutant, the obese ob/ob mouse. Binding studies were thus carried out in brain or peripheral tissues, blood platelets (SERT) and kidneys (TSPO), of ob/ob and WT mice supplied with a standard diet, using the selective radiochemical ligands [3H]-paroxetine and [3H]-PK11195. We observed comparable SERT number or affinity in brain and platelets of ob/ob and WT mice, whilst a significantly higher [3H]-PK11195 density was reported in the brain of ob/ob animals. TSPO binding parameters were similar in the kidneys of all tested mice. By [3H]-PK11195 autoradiography of coronal hypothalamic-hippocampal sections, an increased TSPO signal was detected in the dentate gyrus (hippocampus) and choroids plexus of ob/ob mice, without appreciable changes in the cortex or hypothalamic-thalamic regions. These findings show that TSPO expression is up-regulated in cerebral regions of ob/ob leptin-deficient mice, suggesting a role of the translocator protein in leptin-dependent CNS trophism and metabolism. Unchanged SERT in mutant mice is discussed herein in the context of previous literature as the forerunner to a deeper biochemical investigation.

Tài liệu tham khảo

Lindström P: The physiology of obese-hyperglycemic mice [ob/ob mice]. The Sci World J. 2007, 7: 666-685. Myers MG: Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res. 2004, 59: 287-304. 10.1210/rp.59.1.287. Saito M, Bray GA: Diurnal rhythm for corticosterone in obese (ob/ob) diabetes (db/db) and goldthioglucose-induced obesity in mice. Endocrinology. 1983, 113: 2181-2185. 10.1210/endo-113-6-2181. Beck B: Neuropetides and obesity. Nutrition. 2000, 16: 916-923. 10.1016/S0899-9007(00)00410-X. Collin M, Håkansson-Ovesjö ML, Misane I, Ögren SO, Meister B: Decreased 5-HT transporter mRNA in neurons of the dorsal raphe nucleus and behavioral depression in the obese leptin-deficient ob/ob mouse. Mol Brain Res. 2000, 81: 51-61. 10.1016/S0169-328X(00)00167-4. Murphy DL, Fox MA, Timpano KR, Moya PR, Patterson AM, Holmes A, Lesch KP, Wendland JR: How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems. Neuropharmacology. 2008, 55: 932-960. 10.1016/j.neuropharm.2008.08.034. Batarseh A, Papadopoulos V: Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states. Mol Cell Endocrinol. 2010, 327: 1-12. 10.1016/j.mce.2010.06.013. Falchi AM, Battetta B, Sanna F, Piludu M, Sogos V, Serra M, Melis M, Putzolu M, Diaz G: Intracellular cholesterol changes induced by translocator protein (18 kDa) TSPO/PBR ligands. Neuropharmacology. 2007, 53: 318-329. 10.1016/j.neuropharm.2007.05.016. Rone MB, Fan J, Papadopoulos V: Cholesterol transport in steroid biosynthesis: role of protein-protein interactions and implications in disease state. Biochim Biophys Acta. 2009, 1791: 646-658. Gavish M, Bachman AN, Shoukrun R, Katz Y, Veenman L, Weisinger G, Weizman A: Enigma of the peripehral benzodiazepine receptor. Pharmacol Rev. 1999, 51: 629-650. Pini S, Martini C, Abelli M, Muti M, Gesi C, Montali M, Chelli B, Lucacchini A, Cassano GB: Peripheral-type benzodiazepine receptor binding sites in platelets of patients with panic disorder associated to separation anxiety symptoms. Psychopharmacology. 2005, 181: 407-411. 10.1007/s00213-005-2247-x. Bazzichi L, Giannaccini G, Betti L, Mascia G, Fabbrini L, Italiani P, De Feo F, Giuliano T, Giacomelli C, Rossi A, Lucacchini A, Bombardieri S: Alteration of serotonin transporter density and activity in fibromyalgia. Arthritis Res Ther. 2006, 8: R99-10.1186/ar1982. Bazzichi L, Giannaccini G, Betti L, Italiani P, Fabbrini L, Defeo F, Giacomelli C, Giuliano T, Rossi A, Uccelli A, Giusti L, Mascia G, Lucacchini A, Bombardieri S: Peripheral benzodiazepine receptors on platelets of fibromyalgic patients. Clin Biochem. 2006, 39: 867-872. 10.1016/j.clinbiochem.2006.06.002. Park S, Harrold JA, Widdowson PS, Williams G: Increased binding at 5-HT1A, 5-HT1B and 5-HT2A receptors and 5-HT transporters in diet-induced obese rats. Brain Res. 1999, 847: 90-97. 10.1016/S0006-8993(99)02055-7. Huang XF, Huang X, Han M, Chen F, Storlien L, Lawrence AJ: 5-HT2A/2C receptor and 5-HT transporter densities in mice prone or resistant to chronic high-fat diet-induced obesity: a quantitative autoradiography study. Brain Res. 2004, 1018: 227-235. 10.1016/j.brainres.2004.05.093. Considine RV, Sinha MK, Heiman ML: Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996, 334: 292-295. 10.1056/NEJM199602013340503. Ramos EJB, Meguid MM, Campos ACL, Coelho JCU: Neuropeptide Y, a-melanocyte-stimulating hormone and monoamines in food intake regulation. Nutrition. 2005, 21: 269-279. 10.1016/j.nut.2004.06.021. Jequiert E: Leptin signaling, adiposity and energy balance. Ann NY Acad Sci. 2002, 967: 379-388. 10.1111/j.1749-6632.2002.tb04293.x. Kjerrulf M, Berke Z, Aspegren A, Umaerus M, Nilsson T, Svensson L, Camejo-Hurt E: Reduced cholesterol accumulation by leptin deficient (ob/ob) mouse macrophages. Inflamm Res. 2006, 55: 300-309. 10.1007/s00011-006-0087-8. Giannaccini G, Giusti L, Santini F, Marsili A, Betti L, Mascia G, Pelosini C, Baroni S, Ciregia F, Fabbrini L, Lucacchini A, Vitti P, Pinchera A: Tubby protein in human lymphocytes from normal weight and obese subjects. Clin Biochemistry. 2007, 40: 806-809. 10.1016/j.clinbiochem.2007.03.020. Matarese G, La Cava A: The intricate interface between immune system and metabolism. Trends Immunol. 2004, 25: 193-200. 10.1016/j.it.2004.02.009. Marazziti D, Rossi A, Dell'Osso L, Palego L, Placidi GP, Giannaccini G, Lucacchini A, Cassano GB: Decreased platelet [3H]-paroxetine binding in untreated panic disorder patients. Life Sci. 1999, 65: 2735-2741. 10.1016/S0024-3205(99)00542-1. Marazziti D, Dell'Osso B, Baroni S, Masala I, Di Nasso E, Giannaccini G, Conti L: Decreased density of peripheral benzodiazepine receptors in psychiatric patients after a suicide attempt. Life Sci. 2005, 77: 3268-3275. 10.1016/j.lfs.2005.04.031. Marazziti D, Dell'Osso L, Rossi A, Masala I, Baroni S, Armani A, Giannaccini G, Di Nasso E, Lucacchini A, Cassano GB: Decreased platelet [3H]-paroxetine binding sites in suicide attempters. Psychiatry Res. 2001, 103: 125-131. 10.1016/S0165-1781(01)00281-5. Charnay Y, Cusin I, Vallet PG, Muzzin P, Rohner-Jeanrenaud F, Bouras C: Intracerebroventricular infusion of leptin decreases serotonin transporter binding sites in the frontal cortex of the rat. Neurosci Lett. 2000, 283: 89-92. 10.1016/S0304-3940(00)00951-4. Giannaccini G, Betti L, Palego L, Schmid L, Fabbrini L, Pelosini C, Gargini C, Da Valle Y, Lanza M, Marsili A, Maffei M, Santini F, Vitti P, Pinchera A, Lucacchini A: Human Serotonin Transporter Expression during Megakaryocytic Differentiation of MEG-01 Cells. Neurochem Res. 2010, 35: 628-635. 10.1007/s11064-009-0112-8. Hurley JH, Zhang S, Bye LS, Marshall MS, Depaoli-Roach AA, Guan K, Fox AP, Yu L: Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP-kinase. BMC Neurosci. 2003, 9: 4-10. Giatti S, Pesaresi M, Cavaletti G, Bianchi R, Carozzi V, Lombardi R, Maschi O, Lauria G, Garcia-Segura LM, Caruso D, Melcangi RC: Neuroprotective effects of a ligand of translocator protein-18KDa (Ro5-4864) in experimental diabetic neuropathy. Neuroscience. 2009, 164: 520-529. 10.1016/j.neuroscience.2009.08.005. Rotondo A, Giannaccini G, Betti L, Chiellini G, Marazziti D, Martini C, Lucacchini A, Cassano GB: The serotonin transporter from human brain: Purification and partial characterization. Neurochem Int. 1996, 28: 299-307. 10.1016/0197-0186(95)00080-1. Ramacciotti CE, Coli E, Paoli R, Marazziti D, Dell'Osso L: Serotonergic activity measured by platelet [3H]-paroxetine binding in patients with eating disorders. Psychiatry Res. 2003, 118: 33-38. 10.1016/S0165-1781(03)00059-3. Selleri S, Bruni F, Costagli C, Costanzo A, Guerrini G, Ciciani G, Costa B, Martini C: 2-Arylpyrazolo[1,5-a]pyrimidin-3-yl Acetamides. New Potent and Selective Peripheral Benzodiazepine Receptor Ligands. Bioorg Med Chem. 2001, 9: 2661-2671. 10.1016/S0968-0896(01)00192-4. Martini C, Chelli B, Betti L, Montali M, Mancuso M, Giannaccini G, Rocchi A, Murri L, Siciliano G: Peripheral benzodiazepine binding sites in platelets of patients affected by mitochondrial diseases and large scale mitochondrial DNA rearrangements. Mol Med. 2002, 8: 841-846. Mc Pherson GA: KINETIC, EBDA, LIGAND, LOWRY: A collection of radio-ligand binding analysis programs. 1985, Biosoft, Cambridge. U.K