An application of a new planar positron imaging system (PPIS) in a small animal: MPTP-induced Parkinsonism in mouse

ObjectiveRecent animal PET research has led to the development of PET scanners for small animals. A planar positron imaging system (PPIS) was newly developed to study physiological function in small animals and plants in recent years. To examine the usefulness of PPIS for functional study in small animals, we examined dopaminergic images of mouse striata in MPTP-induced parkinsonism.MethodsMale C57BL/6NCrj mice were treated with MPTP 7 days before the PPIS study. Scans were performed to measure dopamine D1 receptor binding and dopamine transporter availability with [11C]SCH23390 (about 2 MBq) and [su11C]β -CFT (about 2 MBq), respectively. After the PPIS study, dopamine content in the striatum was measured by HPLC.ResultsThe MPTP treatment significantly reduced dopamine content in the striatum 7 days after treatment. In the MPTP-treated group, [11C]β -CFT binding in the striatum was significantly decreased compared with the control group, while striatal [11C]SCH23390 binding was not affected. Dopamine content in the striatum was significantly correlated with the striatal binding of [11C]β -CFT.ConclusionThe present results suggest that PPIS is able to determine brain function in a small animal. Using PPIS, high throughput imaging of small animal brain functions could be achieved.

[1]  R. Heikkila,et al.  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration to C57-black mice leads to parallel decrements in neostriatal dopamine content and tyrosine hydroxylase activity. , 1986, European journal of pharmacology.

[2]  S. Laughlin,et al.  An Energy Budget for Signaling in the Grey Matter of the Brain , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[3]  Hideo Tsukada,et al.  Isoflurane anesthesia enhances the inhibitory effects of cocaine and GBR12909 on dopamine transporter: PET studies in combination with microdialysis in the monkey brain , 1999, Brain Research.

[4]  Y. Kitamura,et al.  Suppressive effect of FK-506, a novel immunosuppressant, against MPTP-induced dopamine depletion in the striatum of young C57BL/6 mice , 1994, Journal of Neuroimmunology.

[5]  K. Tipton,et al.  Advances in Our Understanding of the Mechanisms of the Neurotoxicity of MPTP and Related Compounds , 1993, Journal of neurochemistry.

[6]  D. Wong,et al.  In vivo imaging of baboon and human dopamine transporters by positron emission tomography using [11C]WIN 35,428 , 1993, Synapse.

[7]  J O Rinne,et al.  PET studies on dopamine D1 receptors in the human brain with carbon-11-SCH 39166 and carbon-11-NNC 756. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  Y Tateno,et al.  Dopamine D1 receptors in Parkinson's disease and striatonigral degeneration: a positron emission tomography study. , 1993, Journal of neurology, neurosurgery, and psychiatry.

[9]  J. Hirvonen,et al.  Measurement of Cortical Dopamine D1 Receptor Binding with [11C]SCH 23390: A Test–Retest Analysis , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  M. Nomoto,et al.  Characteristic upregulation of dopamine D1-receptor in rat striatum after 6-hydroxydopamine treatment. , 1996, Japanese journal of pharmacology.

[11]  J. Joyce,et al.  Decreased striatal D1 binding density following mesotelencephalic 6-hydroxydopamine injections: an autoradiographic analysis , 1989, Brain Research.

[12]  J. Langston,et al.  Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. , 1983, Science.

[13]  S. Cherry,et al.  Performance evaluation of microPET: a high-resolution lutetium oxyorthosilicate PET scanner for animal imaging. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[14]  Hideo Tsukada,et al.  Dose–response and duration effects of acute administrations of cocaine and GBR12909 on dopamine synthesis and transporter in the conscious monkey brain: PET studies combined with microdialysis , 2000, Brain Research.

[15]  R. N. Goble,et al.  Performance evaluation of the microPET P4: a PET system dedicated to animal imaging. , 2001, Physics in medicine and biology.

[16]  G L Brownell,et al.  Dopamine fiber detection by [11C]-CFT and PET in a primate model of parkinsonism , 1992, Neuroreport.

[17]  Arion F. Chatziioannou,et al.  Molecular imaging of small animals with dedicated PET tomographs , 2001, European Journal of Nuclear Medicine and Molecular Imaging.

[18]  R. Gainetdinov,et al.  Dopamine Transporter Is Required for In Vivo MPTP Neurotoxicity: Evidence from Mice Lacking the Transporter , 1997, Journal of neurochemistry.

[19]  C D Marsden,et al.  Alterations in striatal and extrastriatal D‐1 and D‐2 dopamine receptors in the MPTP‐treated common marmoset: An autoradiographic study , 1993, Synapse.

[20]  S. Boyce,et al.  Autoradiographic studies in animal models of hemi-parkinsonism reveal dopamine D2 but not D1 receptor supersensitivity. II. Unilateral intra-carotid infusion of MPTP in the monkey (Macaca fascicularis) , 1990, Brain Research.

[21]  S R Cherry,et al.  Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging. , 2001, Physics in medicine and biology.

[22]  T. Yamashita,et al.  A compact planar positron imaging system , 2004 .

[23]  R. Schwartzman,et al.  Dopamine receptor changes in untreated and (+)-PHNO-treated MPTP parkinsonian primates , 1991, Brain Research.

[24]  D. J. Brooks,et al.  In vivo studies on striatal dopamine D1 and D2 site binding in L-dopa-treated Parkinson's disease patients with and without dyskinesias , 1997, Neurology.

[25]  K. Någren,et al.  PET demonstrates different behaviour of striatal dopamine D‐1 and D‐2 receptors in early Parkinson's disease , 1990, Journal of neuroscience research.

[26]  K. Suzuki,et al.  Age-related changes in human D1 dopamine receptors measured by positron emission tomography , 2005, Psychopharmacology.

[27]  W. Nicklas,et al.  Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. , 1985, Life sciences.

[28]  G. Petzinger,et al.  Experimental models of Parkinson's disease: insights from many models. , 1999, Laboratory animal science.