Distribution of SV2C mRNA and protein expression in the mouse brain with a particular emphasis on the basal ganglia system

Dardou, David; Dassesse, Donald; Cuvelier, Laetitia; Deprez, Tania; Ryck, Marc De; Schiffmann, Serge N.

doi:10.1016/j.brainres.2010.09.063

Cited by 55 publications

(69 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Staining patterns observed with our mSV2CpAb were consistent with reports using other SV2C antibodies (37, 38). SV2A and SV2B are strongly expressed throughout the mouse brain, whereas SV2C is preferentially expressed in limited nuclei (Fig.…”

Section: Resultssupporting

confidence: 89%

“…SV2A has been strongly implicated in epilepsy and is the specific pharmacological target for the antiepileptic levetiracetam (36); however, despite extensive research, the molecular function of each of the SV2 proteins has not been fully described. SV2C is distinguished from SV2A and SV2B by its enriched expression in the basal ganglia and preferential localization to dopaminergic cells in mice (37, 38). Intriguingly, SV2C was recently identified as a genetic mediator of one of the most robust environmental modulators of PD risk: nicotine use, which is strongly protective against PD (39, 40).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease

Dunn

Stout

Ozawa

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

112

128

View full text Add to dashboard Cite

SignificanceHere we describe a role for the synaptic vesicle glycoprotein 2C (SV2C) in dopamine neurotransmission and Parkinson disease (PD). SV2C is expressed on the vesicles of dopamine-producing neurons, and genetic deletion of SV2C causes a reduction in synaptic release of dopamine. The reduced dopamine release is associated with a decrease in motor activity. SV2C is suspected of mediating the neuroprotective effects of nicotine, and we show an ablated neurochemical response to nicotine in SV2C-knockout mice. Last, we demonstrate that SV2C expression is specifically disrupted in mice that express mutated α-synuclein and in humans with PD. Together, these data establish SV2C as an important mediator of dopamine homeostasis and a potential contributor to PD pathogenesis.

show abstract

Section: Resultssupporting

confidence: 89%

mentioning

confidence: 99%

Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease

Dunn

Stout

Ozawa

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

112

128

View full text Add to dashboard Cite

show abstract

“…1C). Staining patterns observed with our mSV2CpAb were consistent with published antibodies (34,35). SV2A and SV2B are strongly expressed throughout the mouse brain, whereas SV2C is preferentially expressed in limited nuclei (Fig.…”

Section: Distribution Of Sv2c In Mouse Basal Gangliasupporting

confidence: 85%

“…SV2A has been strongly implicated in epilepsy and is the specific pharmacological target for the antiepileptic levetiracetam; however, despite extensive research the molecular function of SV2 proteins has not been fully described. SV2C is distinguished from SV2A and SV2B by its enriched expression in the basal ganglia and preferential localization to dopaminergic cells in mice (34,35). Intriguingly, SV2C was recently identified as a genetic mediator of one of the most robust environmental modulators of PD risk: nicotine use, which is strongly protective against PD (36,37).…”

Section: Introductionmentioning

confidence: 99%

Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson’s disease

Dunn

Stout

Ozawa

et al. 2016

Preprint

View full text Add to dashboard Cite

The synaptic vesicle glycoprotein 2 (SV2) family of proteins are involved in synaptic function throughout the brain. The ubiquitously expressed SV2A has been widely implicated in epilepsy, though SV2C with its restricted basal ganglia distribution has no known function. SV2C is emerging as a potentially relevant protein in Parkinson's disease, as it is a genetic modifier of nicotine neuroprotection and sensitivity to L-DOPA. Here we identify SV2C as a mediator of dopamine homeostasis and report that disrupted expression of SV2C within the basal ganglia is a pathological feature of Parkinson's disease (PD). Genetic deletion of SV2C leads to reduced dopamine release in the dorsal striatum as measured by fastscan cyclic voltammetry, reduced striatal dopamine content, disrupted alpha-synuclein expression, deficits in motor function, and alterations in neurochemical effects of nicotine. Further, SV2C expression is dramatically altered in postmortem brain tissue from PD cases, but not in Alzheimer's disease, progressive supranuclear palsy or multiple system atrophy. This disruption was paralleled in mice overexpressing mutated α-synuclein. These data establish SV2C as a novel mediator of dopamine neuron function and suggest that SV2C disruption is a unique feature of PD that likely contributes to dopaminergic dysfunction Parkinson's disease | synaptic vesicles | dopamine | SV2C

show abstract

“…In contrast to SV2A, SV2B has a more restricted expression pattern; however, it is widely coexpressed with SV2A in many, but not all, synaptic vesicles of nerve terminals, including the hippocampal pyramidal cells [27, 28]. SV2C displays an even more restricted pattern of expression, which, under physiological conditions, is mainly limited to basal ganglia and the brain stem [29, 30]. SV2A is the only SV2 isoform expressed in many inhibitory, GABAergic neurons [27, 31].…”

Section: The Role Of Sv2a In Modulating Neuronal Excitability In the mentioning

confidence: 99%

Synaptic Vesicle Glycoprotein 2A Ligands in the Treatment of Epilepsy and Beyond

Löscher¹,

et al. 2016

View full text Add to dashboard Cite

The synaptic vesicle glycoprotein SV2A belongs to the major facilitator superfamily (MFS) of transporters and is an integral constituent of synaptic vesicle membranes. SV2A has been demonstrated to be involved in vesicle trafficking and exocytosis, processes crucial for neurotransmission. The anti-seizure drug levetiracetam was the first ligand to target SV2A and displays a broad spectrum of anti-seizure activity in various preclinical models. Several lines of preclinical and clinical evidence, including genetics and protein expression changes, support an important role of SV2A in epilepsy pathophysiology. While the functional consequences of SV2A ligand binding are not fully elucidated, studies suggest that subsequent SV2A conformational changes may contribute to seizure protection. Conversely, the recently discovered negative SV2A modulators, such as UCB0255, counteract the anti-seizure effect of levetiracetam and display procognitive properties in preclinical models. More broadly, dysfunction of SV2A may also be involved in Alzheimer’s disease and other types of cognitive impairment, suggesting potential novel therapies for levetiracetam and its congeners. Furthermore, emerging data indicate that there may be important roles for two other SV2 isoforms (SV2B and SV2C) in the pathogenesis of epilepsy, as well as other neurodegenerative diseases. Utilization of recently developed SV2A positron emission tomography ligands will strengthen and reinforce the pharmacological evidence that SV2A is a druggable target, and will provide a better understanding of its role in epilepsy and other neurological diseases, aiding in further defining the full therapeutic potential of SV2A modulation.

show abstract

Distribution of SV2C mRNA and protein expression in the mouse brain with a particular emphasis on the basal ganglia system

Cited by 55 publications

References 28 publications

Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease

Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease

Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson’s disease

Synaptic Vesicle Glycoprotein 2A Ligands in the Treatment of Epilepsy and Beyond

Contact Info

Product

Resources

About