Localization and Expression of VMAT2 Aross Mammalian Species

Schäfer, Martin; Weihe, Eberhard; Eiden, Lee E.

doi:10.1016/b978-0-12-411512-5.00015-4

Cited by 33 publications

(7 citation statements)

References 59 publications

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“…Tetrabenazine (Vesicular monoamine transporter: VMAT inhibitor) has been used as an effective treatment for refractory TS (Jankovic and Beach, 1997 ). VMAT2 plays an important role in transporting norepinephrine and other monoamines in synaptic vesicles both in the periphery and central nervous system (Ben-Dor et al, 2007 ; Eiden and Weihe, 2011 ; Schafer et al, 2013 ). A significant reduction of platelet VMAT2 is reported in patients with TS indicating, if occurred in the brain, adaptive mechanisms to dopaminergic over reactivity (Ben-Dor et al, 2007 ).…”

Section: Autonomic Activity and Tic Expressionmentioning

confidence: 99%

The role of the autonomic nervous system in Tourette Syndrome

2015

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Tourette Syndrome (TS) is a neurodevelopmental disorder, consisting of multiple involuntary movements (motor tics) and one or more vocal (phonic) tics. It affects up to one percent of children worldwide, of whom about one third continue to experience symptoms into adulthood. The central neural mechanisms of tic generation are not clearly understood, however recent neuroimaging investigations suggest impaired cortico-striato-thalamo-cortical activity during motor control. In the current manuscript, we will tackle the relatively under-investigated role of the peripheral autonomic nervous system, and its central influences, on tic activity. There is emerging evidence that both sympathetic and parasympathetic nervous activity influences tic expression. Pharmacological treatments which act on sympathetic tone are often helpful: for example, Clonidine (an alpha-2 adrenoreceptor agonist) is often used as first choice medication for treating TS in children due to its good tolerability profile and potential usefulness for co-morbid attention-deficit and hyperactivity disorder. Clonidine suppresses sympathetic activity, reducing the triggering of motor tics. A general elevation of sympathetic tone is reported in patients with TS compared to healthy people, however this observation may reflect transient responses coupled to tic activity. Thus, the presence of autonomic impairments in patients with TS remains unclear. Effect of autonomic afferent input to cortico-striato-thalamo-cortical circuit will be discussed schematically. We additionally review how TS is affected by modulation of central autonomic control through biofeedback and Vagus Nerve Stimulation (VNS). Biofeedback training can enable a patient to gain voluntary control over covert physiological responses by making these responses explicit. Electrodermal biofeedback training to elicit a reduction in sympathetic tone has a demonstrated association with reduced tic frequency. VNS, achieved through an implanted device that gives pulsatile electrical stimulation to the vagus nerve, directly modulates afferent interoceptive signals. The potential efficacy of biofeedback/VNS in TS and the implications for understanding the underlying neural mechanisms of tics will be discussed.

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Section: Autonomic Activity and Tic Expressionmentioning

confidence: 99%

The role of the autonomic nervous system in Tourette Syndrome

2015

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“…Our detection of an association between rs363371 and PD only in male Han Chinese contrasts with several lines of evidence implicating VMAT2 in PD pathology. A member of the SLC18A2 family of transporters, which are expressed primarily in the brain, VMAT2, is a 12-pass transmembrane protein [ 4 ] that packages dopamine and neurotoxins into secretion vesicles [ 29 ]. VMAT2 is expressed in the nigrostriatal area at 100-fold higher levels than in cerebellar or cerebral areas, and levels of nigrostriatal VMAT2 are lower in PD patients than in healthy controls [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress has been shown to arise from cytoplasmic dopamine rather than extracellular dopamine [ 3 ]. Homeostasis of cytoplasmic dopamine depends on normal functioning of both the dopamine transporter (DAT), which recycles dopamine from the extracellular medium into the cytoplasm, and the vesicular monoamine transporter 2 (VMAT2), which packages dopamine into vesicles and helps transport it to the extracellular medium [ 4 ]. VMAT2 dysfunction leads to excessive dopamine aggregation in the cytoplasm, where its metabolism generates reactive oxidative species such as ∙ OH, O 2 ∙− , H 2 O 2 , and neurotoxic quinones [ 2 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Polymorphism in theVesicular Monoamine Transporter 2Gene Decreases the Risk of Parkinson’s Disease in Han Chinese Men

Yang

Zhao

et al. 2015

Parkinson's Disease

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Background. Polymorphisms rs363371 and rs363324 in the vesicular monoamine transporter 2 (VMAT2) gene have been associated with risk of PD in an Italian population, and our aim is to investigate the association between the two single-nucleotide polymorphisms and PD in Han Chinese. Methods. 561 Han Chinese PD patients and 491 healthy age- and gender-matched controls were genotyped using Ligase detection reaction (LDR) method. Result. Both of patient and control groups showed similar genotype frequencies between patients and controls at both rs363371 and rs363324, as well as similar minor A allele frequencies at rs363371 (P = 0.452) and rs363324 (P = 0.413). None of the observed haplotypes showed a significant association with PD. Subgroup analysis by gender and age at onset revealed a significant association between the A allele of rs363371 and PD in Han Chinese males relative to healthy controls (OR 0.799, 95% CI 0.665 to 0.959, P = 0.016), and this association remained significant after adjusting for age (OR 0.785, 95% CI 0.652 to 0.945, P = 0.011). Conclusion. These results suggest that polymorphism of VMAT2 locus is associated with risk of PD in Han Chinese overall but that the A allele at rs363371 may protect against PD in Han Chinese males.

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“…Chromogranin A (CgA), a general NE marker, and the more specific markers vesicular monoamine transporter 1 and 2 (VMAT1 and VMAT2) are associated with large dense core vesicles. Other general markers, e.g., synaptophysin (syn) and synaptic vesicle protein 2 (SV2), correspond to small synaptic-like vesicles [1][2][3][4][5]. CgA and syn are cornerstones in the histopathological diagnostics of neuroendocrine tumors (NETs) including NB [6].…”

Section: Introductionmentioning

confidence: 99%

“…VMAT1 and 2 are acidic glycoproteins and part of a larger family of transporters termed as toxin-extruding antiporter system. Both VMATs are responsible for the uptake and storage of the monoamines dopamine, noradrenalin, adrenalin, and 5-hydroxytryptophane/serotonin in synaptic/secretory vesicles [2,3]. VMAT1 is expressed in the enterochromaffin cells of the gastrointestinal tract and in the chromaffin cells of the adrenal medulla [13] while VMAT2 is found in endocrine (e.g., chromaffin cells of the adrenal medulla, enterochromaffin-like cells, ghrelin/obestatin cells, and pancreatic β cells), as well as in non-endocrine cells (e.g., mast cells) [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Synaptic Vesicle Protein 2 and Vesicular Monoamine Transporter 1 and 2 Are Expressed in Neuroblastoma

et al. 2019

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Neuroblastoma (NB), the most common extracranial cancer in childhood, exhibits neuroendocrine (NE) differentiation. Two well-established NE markers, chromogranin A (CgA) and synaptophysin (syn), are used in the histopathological diagnostics. Our aims were to explore if the NE markers synaptic vesicle protein 2 (SV2) and vesicular monoamine transporter 1 (VMAT1) and 2 (VMAT2) also are expressed in human NB and if so, evaluate their usefulness in NB histopathological diagnostics. Tumor specimens from 21 NB patients, before and/or after chemotherapy, were immunostained for CgA, syn, SV2, VMAT1, and VMAT2. Clinical data was extracted from patients' records. SV2 was highly expressed in NB, as was CgA while syn was less frequently expressed compared to the other two. Both VMATs were expressed in several NB, VMAT2 in more cases than VMAT1 and its expression was similar to syn. Chemotherapy did not affect the immunoreactivity in an obvious way. SV2 was highly expressed in NB and can thus be useful marker in NB diagnostics. VMAT1 and VMAT2 were also expressed in NB but similar to syn less reliable as tumor markers.

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Localization and Expression of VMAT2 Aross Mammalian Species

Cited by 33 publications

References 59 publications

The role of the autonomic nervous system in Tourette Syndrome

The role of the autonomic nervous system in Tourette Syndrome

Polymorphism in theVesicular Monoamine Transporter 2Gene Decreases the Risk of Parkinson’s Disease in Han Chinese Men

Synaptic Vesicle Protein 2 and Vesicular Monoamine Transporter 1 and 2 Are Expressed in Neuroblastoma

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