Analysis of VMAT2 Binding After Methamphetamine or MPTP Treatment
| Autor: | Kelly A. Hogan, Patricia K. Sonsalla, Roland G. W. Staal |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty Dopamine Dopamine Agents Tetrabenazine Biochemistry Synaptic vesicle Methamphetamine Dihydrotetrabenazine Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Vesicular Biogenic Amine Transport Proteins Internal medicine medicine Animals Membrane Glycoproteins MPTP Histological Techniques Neuropeptides Membrane Transport Proteins Meth Ligand (biochemistry) Corpus Striatum Vesicular monoamine transporter Endocrinology chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Vesicular Monoamine Transport Proteins Central Nervous System Stimulants Synaptic Vesicles Synaptosomes medicine.drug |
| Zdroj: | Journal of Neurochemistry. 74:2217-2220 |
| ISSN: | 0022-3042 |
| DOI: | 10.1046/j.1471-4159.2000.0742217.x |
| Popis: | [3H]Dihydrotetrabenazine ([3H]DTBZ), a specific ligand for the vesicular monoamine transporter (VMAT2), has been used to characterize the integrity of monoaminergic nerve terminals in experimental animals and humans. The purpose of the present studies was to compare the loss of VMAT2 binding with the loss of other neurochemical markers of the dopamine (DA) nerve terminals in mice treated with neurotoxic doses of methamphetamine (METH) or MPTP. Profound decreases (> or =70%) in DA content, tyrosine hydroxylase activity, and PH]carbomethoxy-3-(4-fluorophenyl)tropane binding to the DA transporter were observed in striatal homogenates at both 1 and 6 days after exposure to the neurotoxins. It is surprising that no significant loss of [3H]DTBZ binding in the homogenates was observed at 1 day after exposure, although a significant loss (-50%) was apparent 6 days later. However, in isolated vesicle preparations, [3H]DTBZ binding and active [3H]DA uptake were markedly reduced (>70%) at 1 day. These observations indicate that vesicle function is compromised at an early time point after exposure to neurotoxic insult. Furthermore, the changes in [H]DTBZ binding in homogenates may not be a sensitive indicator of early damage to synaptic vesicles, although homogenate binding reliably identifies a loss of VMAT2 at later times. |
| Databáze: | OpenAIRE |
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