Drastic decrease in dopamine receptor levels in the striatum of acetylcholinesterase knock-out mouse |
| |
| Authors: | Anna Hrabovska Vladimir Farar Veronique Bernard Ellen G Duysen Jiri Brabec Oksana Lockridge Jaromir Myslivecek |
| |
| Institution: | 1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia;2. INSERM U686, Biologie des Jonctions Neuromusculaires, 45 rue des Saints-Pères, 75006 Paris, France;3. University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198-6805, United States;4. Institute of Anatomy, 1st Faculty of Medicine, Charles University, U Nemocnice 3, 128 00 Prague, Czech Republic;5. Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic;1. Institute of Chemical Biology, Ilia State University, 3/5 K. Cholokhashvili Avenue, 0162 Tbilisi, Georgia;2. Department of Brain Ultrastructure and Nanoarchitecture, I. Beriitashvili Center of Experimental BioMedicine, 14, Gotua Street, 0160 Tbilisi, Georgia;3. New Vision University, 1A Evgeni Mikeladze Street, 0158 Tbilisi, Georgia;1. Laboratorio de Biología de la Reproducción (LABIR), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina;2. Laboratorio de Medicina Experimental y Traduccional (LME&T), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina;3. Laboratorio de Cronobiología (LABCRON), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina;4. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis (IMIBIO-SL), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina;3. From the Departments of Molecular Therapeutics and Neuroscience, The Scripps Research Institute, Jupiter, Florida 33458,;4. the Mailman Research Center, McLean Hospital, Belmont, Massachusetts 02478, and;5. the Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02215 |
| |
| Abstract: | BackgroundThe acetylcholinesterase knock-out mouse lives to adulthood despite 60-fold elevated acetylcholine concentrations in the brain that are lethal to wild-type animals. Part of its mechanism of survival is a 50% decrease in muscarinic and nicotinic receptors and a 50% decrease in adrenoceptor levels.HypothesisThe hypothesis was tested that the dopaminergic neuronal system had also adapted.MethodsRadioligand binding assays measured dopamine receptor level and binding affinity in the striatum. Immunohistochemistry of brain sections with specific antibodies visualized dopamine transporter. Effects on the intracellular compartment were measured as cAMP content, PI-phospholipase C activity.ResultsDopamine receptor levels were decreased 28-fold for the D1-like, and more than 37-fold for the D2-like receptors, though binding affinity was normal. Despite these huge changes in receptor levels, dopamine transporter levels were not affected. The intracellular compartment had normal levels of cAMP and PI-phospholipase C activity.ConclusionSurvival of the acetylcholinesterase knock-out mouse could be linked to adaptation of many neuronal systems during development including the cholinergic, adrenergic and dopaminergic. These adaptations balance the overstimulation of cholinergic receptors caused by high acetylcholine concentrations and thus maintain homeostasis inside the cell, allowing the animal to live. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
