Psychostimulants, Brain Membrane Lipids and Dopamine Transmission

Chen, Rong

doi:10.4172/2167-7956.1000143

Cited by 4 publications

(2 citation statements)

References 54 publications

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“…This observation suggests that SMA is a suitable new alternative for membrane protein purification enabling the study of the different GPCR signalling pathways in a more native environment than the detergent setting. To emphasise how crucial the protein-lipid environment is for ligand binding or protein signalling, it has been demonstrated that dopamine receptors, upon interaction with certain drugs such as cocaine, are able to translocate to a different lipid environment [60,61]. Thus, the ability to directly extract proteins in their preferred local lipid composition using SMA Lipodisqs may offer significant advantages over current approaches.…”

Section: Radio-ligand Binding Assaysmentioning

confidence: 99%

Detergent-free extraction of a functional low-expressing GPCR from a human cell line

Juarez

Muñoz–García

Reis

et al. 2020

Biochimica et Biophysica Acta (BBA) - Biomembranes

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Radio-ligand Binding Assaysmentioning

confidence: 99%

Detergent-free extraction of a functional low-expressing GPCR from a human cell line

Juarez

Muñoz–García

Reis

et al. 2020

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

show abstract

“…Concerning dopamine neurotransmission, using super-resolution microscopy, it has been shown that the dopaminergic transporter (DAT) may be sequestrated in cholesterol-dependent nanodomains in the membrane of presynaptic neurons and that cholesterol depletion reduces localization of the DAT in these nanodomains (Rahbek-Clemmensen et al, 2017). Other evidences suggest that cholesterol dysregulation may alter the DAT functioning (Jones et al, 2012; Luessen and Chen, 2016; Zeppelin et al, 2018). Thus, it is possible that if cholesterol homeostasis is dysregulated, the functioning of the dopamine system and eventually the response to future exposure to drugs may be changed, which may in turn increase the risks of addiction.…”

Section: Discussionmentioning

confidence: 99%

Persistent Neuroadaptations in the Expression of Genes Involved in Cholesterol Homeostasis Induced by Chronic, Voluntary Alcohol Intake in Rats

Alsebaaly

Dugast

Favot

et al. 2018

Front. Mol. Neurosci.

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Alcohol use disorder (AUD) is associated with persistent adaptations in the brain that are believed to participate in the long-lasting vulnerability to relapse after abstinence. Cholesterol, the major sterol compound found in the central nervous system (CNS), plays a major role in maintenance of neuronal morphology, synaptogenesis and synaptic communication and may be involved in alcohol-induced neuroadaptations. In this study, we investigated whether alcohol consumption in a two-bottle choice paradigm followed by 3 weeks of abstinence could alter the expression of genes encoding proteins involved in cholesterol homeostasis in brain regions involved in addiction and relapse, namely the prefrontal cortex (PFC), the nucleus accumbens (NAc), the mesencephalon and the amygdala. We found that voluntary alcohol intake followed by 3 weeks of forced abstinence produces changes in the transcription of several genes encoding proteins directly involved in cholesterol synthesis such as 3-hydroxyl-3-methylglutaryl-coenzyme A (HMGCoA) reductase, farnesyl-diphosphate farnesyltransferase 1 (FDFT1) and farnesyl diphosphate synthase (FDPS) and in its regulation such as sterol regulatory element-binding factor-2 (SREBF2), in cholesterol transport such as ATP-binding cassette subfamily A member 1 (ABCA1) and in cholesterol degradation such as CYP46A1. Interestingly, these changes appeared to be region-specific and suggest that previous chronic exposure to alcohol might durably increase cholesterol metabolism in the PFC, the NAc and the mesencephalon and decrease cholesterol metabolism in the amygdala. Altogether, these results suggest that alcohol consumption leads to durable deregulations in cholesterol metabolism in key areas involved in loss of control over drug use and addiction. These long-term neuroadaptations may participate in the changes in brain structure and functioning that are responsible for the long-lasting risks of relapse to alcohol.

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A Perspective: Active Role of Lipids in Neurotransmitter Dynamics

Postila

Róg

2019

Mol Neurobiol

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Synaptic neurotransmission is generally considered as a function of membrane-embedded receptors and ion channels in response to the neurotransmitter (NT) release and binding. This perspective aims to widen the protein-centric view by including another vital component-the synaptic membrane-in the discussion. A vast set of atomistic molecular dynamics simulations and biophysical experiments indicate that NTs are divided into membrane-binding and membrane-nonbinding categories. The binary choice takes place at the water-membrane interface and follows closely the positioning of the receptors' binding sites in relation to the membrane. Accordingly, when a lipophilic NT is on route to a membrane-buried binding site, it adheres on the membrane and, then, travels along its plane towards the receptor. In contrast, lipophobic NTs, which are destined to bind into receptors with extracellular binding sites, prefer the water phase. This membrane-based sorting splits the neurotransmission into membraneindependent and membrane-dependent mechanisms and should make the NT binding into the receptors more efficient than random diffusion would allow. The potential implications and notable exceptions to the mechanisms are discussed here. Importantly, maintaining specific membrane lipid compositions (MLCs) at the synapses, especially regarding anionic lipids, affect the level of NT-membrane association. These effects provide a plausible link between the MLC imbalances and neurological diseases such as depression or Parkinson's disease. Moreover, the membrane plays a vital role in other phases of the NT life cycle, including storage and release from the synaptic vesicles, transport from the synaptic cleft, as well as their synthesis and degradation.

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Psychostimulants, Brain Membrane Lipids and Dopamine Transmission

Cited by 4 publications

References 54 publications

Detergent-free extraction of a functional low-expressing GPCR from a human cell line

Detergent-free extraction of a functional low-expressing GPCR from a human cell line

Persistent Neuroadaptations in the Expression of Genes Involved in Cholesterol Homeostasis Induced by Chronic, Voluntary Alcohol Intake in Rats

A Perspective: Active Role of Lipids in Neurotransmitter Dynamics

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