Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging

We present development and human application of a method for determining the regional cerebral density of the type 2 vesicular monoamine transporter (VMAT2) using positron emission tomography (PET) and [11C]dihydrotetrabenazine (DTBZ). Previous animal studies indicate striatal VMAT2 density is linearly related to the integrity of substantia nigra dopamine neurons and is not subject to drug‐or lesion‐compensatory regulation. In the present studies, kinetic compartmental modeling was employed to estimate blood‐brain [11C]DTBZ transport (K1,) and VMAT2 binding site density (tissue‐to‐plasma DTBZ distribution volume, DV)from the cerebral and plasma DTBZ time courses her intravenous tracer injection. In controls, we found reductions of putamen DTBZ DV with advancing age, corresponding to losses of 0.77% per year in specific VMAT2 binding. Parkinson's disease (PD) patients had reduction in specific DTBZ DV in the putamen (−61%) and in the caudate nucleus (−43%). There was no overlap of lowest specific putamen DTBZ DV between individual elderly controls and PD patients. The present results indicate the suitability of [11C]DTBZ PET for objective quantification of nigrostriatal integrity, including evaluation of PD progression and its possible therapeutic modification.

[1]  D. E. Kuhl,et al.  Kinetic Evaluation of [11C]Dihydrotetrabenazine by Dynamic PET: Measurement of Vesicular Monoamine Transporter , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  K. Frey,et al.  Effects of dopaminergic drug treatments on in vivo radioligand binding to brain vesicular monoamine transporters. , 1996, Nuclear medicine and biology.

[3]  K. Frey,et al.  The vesicular monoamine transporter is not regulated by dopaminergic drug treatments. , 1995, European journal of pharmacology.

[4]  R. Koeppe,et al.  In vivo imaging of the brain vesicular monoamine transporter. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  D. Kuhl,et al.  [3H]methoxytetrabenazine: A high specific activity ligand for estimating monoaminergic neuronal integrity , 1995, Neuroscience.

[6]  Eileen O. Smith,et al.  Decreased single‐photon emission computed tomographic {123I}β‐CIT striatal uptake correlates with symptom severity in parkinson's disease , 1995, Annals of neurology.

[7]  A. Gjedde,et al.  Regulation of DOPA Decarboxylase Activity in Brain of Living Rat , 1995, Journal of neurochemistry.

[8]  J. Haycock,et al.  Striatal 3,4‐dihydroxyphenylalanine decarboxylase in aging: Disparity between postmortem and positron emission tomography studies? , 1995, Annals of neurology.

[9]  D. Charney,et al.  Age-Related Decline in Striatal Dopamine Transporter Binding with Iodine-123-β-CITSPECT , 1995 .

[10]  K. Frey,et al.  Binding of α-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific , 1995 .

[11]  J. Haycock,et al.  Striatal dihydroxyphenylalanine decarboxylase and tyrosine hydroxylase protein in idiopathic Parkinson's disease and dominantly inherited olivopontocerebellar atrophy , 1995, Movement disorders : official journal of the Movement Disorder Society.

[12]  S. Gilman,et al.  Decreased striatal monoaminergic presynaptic terminals in OPCA and MSA demonstrated with [11C]dihydrotetrabenazine and PET. , 1995 .

[13]  S. Lehéricy,et al.  Monoamine vesicular uptake sites in patients with Parkinson's disease and Alzheimer's disease, as measured by tritiated dihydrotetrabenazine autoradiography , 1994, Brain Research.

[14]  M Schulzer,et al.  Age‐dependent decline of nigrostriatal dopaminergic function: A positron emission tomographic study of grandparents and their grandchildren , 1994, Annals of neurology.

[15]  J. O. Schenk,et al.  The Striatal Transporter for Dopamine in the Rat May Be Kinetically Up‐Regulated Following 3 Weeks of Withdrawal from Cocaine Self‐Administration , 1994, Journal of neurochemistry.

[16]  C. Marsden,et al.  Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia , 1994, Annals of neurology.

[17]  J S Fowler,et al.  Decreased dopamine transporters with age in healthy human subjects , 1994, Annals of neurology.

[18]  L. Naudon,et al.  Short-term treatments with haloperidol or bromocriptine do not alter the density of the monoamine vesicular transporter in the substantia nigra , 1994, Neuroscience Letters.

[19]  S J Kish,et al.  Heterogeneous subregional binding patterns of 3H-WIN 35,428 and 3H-GBR 12,935 are differentially regulated by chronic cocaine self- administration , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  G. Sawle,et al.  Separating Parkinson's disease from normality. Discriminant function analysis of fluorodopa F 18 positron emission tomography data. , 1994, Archives of neurology.

[21]  D E Kuhl,et al.  [11C]Tropanyl Benzilate—Binding to Muscarinic Cholinergic Receptors: Methodology and Kinetic Modeling Alternatives , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  L. Eiden,et al.  Functional Identification and Molecular Cloning of a Human Brain Vesicle Monoamine Transporter , 1993, Journal of neurochemistry.

[23]  S. Fahn,et al.  Chronic levodopa administration alters cerebral mitochondrial respiratory chain activity , 1993, Annals of neurology.

[24]  Alan C. Evans,et al.  Striatal L‐DOPA Decarboxylase Activity in Parkinson's Disease In Vivo: Implications for the Regulation of Dopamine Synthesis , 1993, Journal of neurochemistry.

[25]  C. Patlak,et al.  Striatal 18F-DOPA Uptake: Absence of an Aging Effect , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  S H Snyder,et al.  Positron emission tomographic imaging of the dopamine transporter with 11C‐WIN 35,428 reveals marked declines in mild Parkinson's disease , 1993, Annals of neurology.

[27]  A. Boulton,et al.  Regulation of striatal aromatic L-amino acid decarboxylase: effects of blockade or activation of dopamine receptors. , 1993, European journal of pharmacology.

[28]  J. Hubble,et al.  Aromatic L‐Amino Acid Decarboxylase Activity of Mouse Striatum Is Modulated via Dopamine Receptors , 1993, Journal of neurochemistry.

[29]  A. Rajput,et al.  Environmental causation of Parkinson's disease. , 1993, Archives of neurology.

[30]  N. Neff,et al.  Evidence for Cyclic AMP‐Mediated Increase of Aromatic L‐Amino Acid Decarboxylase Activity in the Striatum and Midbrain , 1993, Journal of neurochemistry.

[31]  R. Koeppe,et al.  In Vivo Imaging of Vesicular Monoamine Transporters in Human Brain Using [11C]Tetrabenazine and Positron Emission Tomography , 1993, Journal of neurochemistry.

[32]  J. DaSilva,et al.  Synthesis of [11C]tetrabenazine, a vesicular monoamine uptake inhibitor, for PET imaging studies. , 1993, Applied Radiation and Isotopes.

[33]  M. Brin,et al.  Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. , 1993, The New England journal of medicine.

[34]  S. Fahn,et al.  The oxidant stress hypothesis in Parkinson's disease: Evidence supporting it , 1992, Annals of neurology.

[35]  C. Marsden,et al.  New insights into the cause of Parkinson's disease , 1992, Neurology.

[36]  S. Kish,et al.  Striatal monoamine neurotransmitters and metabolites in dominantly inherited olivopontocerebellar atrophy , 1992, Neurology.

[37]  J. Palacios,et al.  Mesostriatal and mesolimbic dopamine uptake binding sites are reduced in Parkinson's disease and progressive supranuclear palsy: A quantitative autoradiographic study using [3H]mazindol , 1992, Neuroscience.

[38]  R. Hichwa,et al.  In vivo Muscarinic Cholingeric Receptor Imaging in Human Brain with [11C]Scopolamine and Positron Emission Tomography , 1992 .

[39]  R. Hichwa,et al.  In vivo muscarinic cholinergic receptor imaging in human brain with [11C]scopolamine and positron emission tomography. , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[40]  R. Koeppe,et al.  Parametric in vivo imaging of benzodiazepine receptor distribution in human brain , 1991, Annals of neurology.

[41]  A. Lees,et al.  Ageing and Parkinson's disease: substantia nigra regional selectivity. , 1991, Brain : a journal of neurology.

[42]  M. Kaufman,et al.  Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson's‐diseased striatum , 1991, Synapse.

[43]  Alan C. Evans,et al.  Dopa decarboxylase activity of the living human brain. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[44]  P. Seeman,et al.  The Dopamine Transporter Is Absent in Parkinsonian Putamen and Reduced in the Caudate Nucleus , 1991, Journal of neurochemistry.

[45]  Richard S. J. Frackowiak,et al.  Striatal function in normal aging: Implications for Parkinson's disease , 1990, Annals of neurology.

[46]  T Jones,et al.  The nigrostriatal dopaminergic system assessed in vivo by positron emission tomography in healthy volunteer subjects and patients with Parkinson's disease. , 1990, Archives of neurology.

[47]  C. Tanner,et al.  Do environmental toxins cause Parkinson's disease? A critical review , 1990, Neurology.

[48]  C. Prasad,et al.  Neuropeptide-dopamine interactions. V. Cyclo(His-Pro) regulation of striatal dopamine transporter complex , 1990, Peptides.

[49]  J. De Keyser,et al.  Age‐related changes in the human nigrostriatal dopaminergic system , 1990, Annals of neurology.

[50]  Y. Agid,et al.  Striatal dopamine deficiency in parkinson's disease: Role of aging , 1989, Annals of neurology.

[51]  C. Patlak,et al.  Nigrostriatal function in humans studied with positron emission tomography , 1989, Annals of neurology.

[52]  H. L. Wiener,et al.  Chronic L-deprenyl-induced up-regulation of the dopamine uptake carrier. , 1989, European journal of pharmacology.

[53]  C. Prasad Neuropeptide-dopamine interactions III. Cyclo(His-Pro) and persistence of dopaminergic supersensitivity on withdrawal from one year continous neuroleptic treatment , 1988, Schizophrenia Research.

[54]  G. Reynolds,et al.  Depletion of monoamine transmitters by tetrabenazine in brain tissue in Huntington's disease , 1988, Neuropharmacology.

[55]  S. Kish,et al.  Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. , 1988, The New England journal of medicine.

[56]  Y. Agid,et al.  [3H]Dihydrotetrabenazine, a New In Vitro Monoaminergic Probe for Human Brain , 1988, Journal of neurochemistry.

[57]  J. Kleinman,et al.  Decreased density of human striatal dopamine uptake sites with age. , 1986, European Journal of Pharmacology.

[58]  D. Goldstein Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System , 1985 .

[59]  N. Alpert,et al.  Strategy for the Measurement of Regional Cerebral Blood Flow Using Short-Lived Tracers and Emission Tomography , 1984, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[60]  C. Nahmias,et al.  Dopamine visualized in the basal ganglia of living man , 1983, Nature.

[61]  R. Wurtman,et al.  Partial lesions of the dopaminergic nigrostriatal system in rat brain: biochemical characterization , 1980, Brain Research.

[62]  P. Mcgeer,et al.  Aging and extrapyramidal function. , 1977, Archives of neurology.

[63]  K. Jellinger,et al.  Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. , 1973, Journal of the neurological sciences.

[64]  B. Djahanguiri,et al.  The prevention of acute gastric ulcer in the rat by alpha-methyldopa. , 1967, Medicina et pharmacologia experimentalis. International journal of experimental medicine.

[65]  O. Hornykiewicz Dopamine (3-hydroxytyramine) and brain function. , 1966, Pharmacological reviews.

[66]  J. Olszewski,et al.  Progressive Supranuclear Palsy: A Heterogeneous Degeneration Involving the Brain Stem, Basal Ganglia and Cerebellum With Vertical Gaze and Pseudobulbar Palsy, Nuchal Dystonia and Dementia , 1964 .

[67]  D. Marquardt An Algorithm for Least-Squares Estimation of Nonlinear Parameters , 1963 .