Abstract:
:The distribution and density of neurons within the brain poses many challenges when making quantitative measurements of neurotransmission in the extracellular space. A volume neurotransmitter is released into the synapse during chemical communication and must diffuse through the extracellular space to an implanted sensor for real-time in situ detection. Fast-scan cyclic voltammetry is an excellent technique for measuring biologically relevant concentration changes in vivo; however, the sensitivity is limited by mass-transport-limited adsorption. Due to the resistance to mass transfer in the brain, the response time of voltammetric sensors is increased, which decreases the sensitivity and the temporal fidelity of the measurement. Here, experimental results reveal how the tortuosity of the extracellular space affects the response of the electrode. Additionally, a model of mass-transport-limited adsorption is utilized to account for both the strength of adsorption and the magnitude of the diffusion coefficient to calculate the response time of the electrode. The response time is then used to determine the concentration of dopamine released in response to salient stimuli. We present the method of kinetic calibration of in vivo voltammetric data and apply the method to discern changes in the KM for the murine dopamine transporter. The KM increased from 0.32 ± 0.08 μM (n = 3 animals) prior to drug administration to 2.72 ± 0.37 μM (n = 3 animals) after treatment with GBR-12909.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Atcherley CW,Laude ND,Monroe EB,Wood KM,Hashemi P,Heien MLdoi
10.1021/cn500020ssubject
Has Abstractpub_date
2015-09-16 00:00:00pages
1509-16issue
9issn
1948-7193journal_volume
6pub_type
杂志文章abstract::Alcohol abuse is a chronic disease characterized by the consumption of alcohol at a level that interferes with physical and mental health and causes serious and persistent changes in the brain. Lipid metabolism is of particular interest due to its high concentration in the brain. Lipids are the main component of cell ...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.6b00120
更新日期:2016-08-17 00:00:00
abstract::Serotonin (5-HT) is a key player in many physiological processes in both the adult organism and developing embryo. One of the mechanisms for 5-HT-mediated effects is covalent binding of 5-HT to the target proteins catalyzed by transglutaminases (serotonylation). Despite the implication in a variety of physiological pr...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.9b00346
更新日期:2019-08-21 00:00:00
abstract::The discovery of haloperidol catalyzed a breakthrough in our understanding of the biochemical basis of schizophrenia, improved the treatment of psychosis, and facilitated deinstitutionalization. In doing so, it solidified the role for chemical neuroscience as a means to elucidate the molecular underpinnings of complex...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00018
更新日期:2017-03-15 00:00:00
abstract::We recently found that tamoxifen suppresses l-glutamate transport activity of cultured astrocytes. Here, in an attempt to separate the l-glutamate transporter-inhibitory activity from the estrogen receptor-mediated genomic effects, we synthesized several compounds structurally related to tamoxifen. Among them, we iden...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn200091w
更新日期:2012-02-15 00:00:00
abstract::Deltorphins are naturally occurring peptides produced by the skin of the giant monkey frog (Phyllomedusa bicolor). They are δ-opioid receptor-selective agonists. Herein, we report the design and synthesis of a peptide, Tyr-d-Ala-(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [d-Ala(2)]deltorphin II template, wh...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.5b00060
更新日期:2015-06-17 00:00:00
abstract::Fast scan cyclic voltammetry in brain slices (slice voltammetry) has been used over the last several decades to increase substantially our understanding of the complex local regulation of dopamine release and uptake in the striatum. This technique is routinely used for the study of changes that occur in the dopamine s...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/cn400026v
更新日期:2013-05-15 00:00:00
abstract::Previous work has established that D-serine (D-Ser) plays important roles in certain neurological processes. Study on its uptake/storage and release by neuronal cells is highly significant for elucidating relevant mechanisms. In this work, PC-12 cells were incubated with racemic Ser (100 μM each enantiomer). After inc...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn5003122
更新日期:2015-04-15 00:00:00
abstract::Ionic zinc is found at a high concentration in some glutamatergic vesicles of the mammalian brain. Ionic zinc is also found chelated to macromolecules in the extracellular space, constituting what has been called the "zinc veneer". In this communication we show that the zinc ionophore, pyrithione, can be used to demon...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn300061z
更新日期:2012-10-17 00:00:00
abstract::Currently, anti-AD drug discovery using target-based approaches is extremely challenging due to unclear etiology of AD and absence of validated therapeutic protein targets. Neuronal death, regardless of causes, plays a key role in AD progression, and it is directly linked to neuroinflammation. Meanwhile, phenotypic sc...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.6b00125
更新日期:2016-11-16 00:00:00
abstract::Central norepinephrine (NE) and dopamine (DA) are involved in a variety of physiological functions and behaviors. Accumulating evidence suggests that NE neurons originating from the locus coeruleus (LC) innervate DA neurons of the ventral tegmental area (VTA) and influence VTA-DA neural activity. However, the underlyi...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00078
更新日期:2017-09-20 00:00:00
abstract::Development of pharmacological tools for the ionotropic glutamate receptors (iGluRs) is imperative for the study and understanding of the role and function of these receptors in the central nervous system. We report the synthesis of 18 analogues of (2 S,3 R)-2-carboxy-3-pyrrolidine acetic acid (3a), which explores the...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.9b00205
更新日期:2019-06-19 00:00:00
abstract::Oligomers of amyloid-β (AβO) are deemed key in synaptotoxicity and amyloid seeding of Alzheimer's disease (AD). However, the heterogeneous and dynamic nature of AβO and inadequate markers for AβO subtypes have stymied effective AβO identification and therapeutic targeting in vivo. We identified an AβO-subclass epitope...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00469
更新日期:2018-07-18 00:00:00
abstract::Dopamine (DA) is a neurotransmitter implicated in multiple functions, including movement, cognition, motivation, and reward. The DA transporter (DAT) is responsible for clearing extracellular DA, thereby terminating DA neurotransmission. Previously, it has been shown that insulin signaling through protein kinase B/Akt...
journal_title:ACS chemical neuroscience
pub_type: 信件
doi:10.1021/cn100031t
更新日期:2010-07-21 00:00:00
abstract::The pathogenesis of Parkinson's disease (PD) is multifactorial event. Combination therapies might be more effective in controlling the disease. Thus, the studies reported were designed to test the hypothesis that gastrodin (GAS)-induced de novo synthesis of nuclear factor E2-related factor 2 (Nrf2) and isorhynchophyll...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00247
更新日期:2018-03-21 00:00:00
abstract::Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding th...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn500049n
更新日期:2014-05-21 00:00:00
abstract::The propagation of pathological proteins throughout the brain is the primary physiological hallmark of the progression of Alzheimer's Disease (AD). A growing body of evidence indicates that hyperphosphorylated Tau proteins are spread transcellularly between neurons in a prionlike fashion, inducing misfolding and aggre...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00531
更新日期:2020-11-04 00:00:00
abstract::In humans, genetic defects of the synthesis or regeneration of tetrahydrobiopterin (BH4), an essential cofactor in hydroxylation reactions, are associated with severe neurological disorders. The diagnosis of these conditions relies on the determination of BH4, dihydrobiopterin (BH2), and dihydroneopterin (NH2) in cere...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn4001928
更新日期:2014-07-16 00:00:00
abstract::Cognitive dysfunctions, including impaired attention, learning, memory, and problem solving, occur in psychiatric diseases, such as depression, and are a hallmark of aging. Altered GABAergic signaling is similarly reported across these conditions, but therapeutic approaches are limited by pan-receptor activities of be...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.9b00148
更新日期:2019-05-15 00:00:00
abstract::Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc). Although both iron accumulation and a defective autophagy-lysosome pathway contribute to the pathological development of PD, the connection between...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/acschemneuro.8b00390
更新日期:2019-02-20 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, with a 10% genetic linkage, of which 20% of these cases may be attributed to mutations in superoxide dismutase (SOD1). Specific mutations in SOD1 have been associated with disease duration, which can be highly variable ranging from a life...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00140
更新日期:2017-10-18 00:00:00
abstract::The efficacy of positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 4 (mGlu4) in preclinical rodent models of Parkinson's disease has been established by a number of groups. Here, we report an advanced preclinically characterized mGlu4 PAM, N-(3-chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.6b00035
更新日期:2016-09-21 00:00:00
abstract::Dendritic spines are the postsynaptic sites for the majority of excitatory synapses in the mammalian forebrain. While many spines display great stability, others change shape in a matter of seconds to minutes. These rapid alterations in dendritic spine number and size require tight control of the actin cytoskeleton, t...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn100012x
更新日期:2010-05-19 00:00:00
abstract::SARS-CoV-2 remains a significant burden on human health. Several lines of evidence suggest that surveillance of sewage and waste can provide an early warning sign for COVID-19 recurrence in a community. In support, SARS-CoV-2 traces were found in sewage in several countries. With this in mind, it is notable that pests...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/acschemneuro.0c00312
更新日期:2020-07-01 00:00:00
abstract::Aminorex (5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) and 4-methylaminorex (4-methyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) are psychostimulants that have long been listed in Schedules IV and I of the UN Convention on Psychotropic Substances of 1971. However, a range of psychoactive analogues exist that are not interna...
journal_title:ACS chemical neuroscience
pub_type: 历史文章,杂志文章,评审
doi:10.1021/acschemneuro.8b00415
更新日期:2018-10-17 00:00:00
abstract::Alzheimer's disease (AD) is a significant health crisis, and current treatments provide only limited benefits to cognition at the cost of serious side effects. Recently, virtual screening techniques such as ligand-based virtual screening (LBVS) and structure-based virtual screening (SBVS) have emerged as powerful drug...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00627
更新日期:2021-01-06 00:00:00
abstract::An in vitro model of ischemic cerebral stroke [oxygen-glucose deprivation (OGD) for 6 h followed by 24 h reoxygenation (R)] with PC12 cells increases Ca(2+) influx by upregulating native L-type Ca(2+) channels and reactive oxygen species (ROS) generation. This reactive oxygen species generation and increase in intrace...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn300143m
更新日期:2013-02-20 00:00:00
abstract::MMP-9 plays a detrimental role in the pathology of several neurological diseases and, thus, represents an important target for intervention. The water-soluble prodrug ND-478 is hydrolyzed to the active MMP-9 inhibitor ND-322, which in turn is N-acetylated to the even more potent metabolite ND-364. We used a sensitive ...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn400077d
更新日期:2013-08-21 00:00:00
abstract::The abnormal aggregation of α-synuclein (α-Syn) is closely associated with Parkinson's disease. Different post-translational modifications of α-Syn have been identified and contribute distinctly in α-Syn aggregation and cytotoxicity. Recently, α-Syn was reported to be N-terminally acetylated in cells, yet the function...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00250
更新日期:2017-10-18 00:00:00
abstract::Early diagnosis in Alzheimer's disease (AD), prior to the appearance of marked clinical symptoms, is critical to prevent irreversible neuronal damage and neural malfunction that lead to dementia and death. Therefore, there is an urgent need to generate new contrast agents which reveal by a noninvasive method the prese...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00260
更新日期:2018-05-16 00:00:00
abstract::The fibrillogenesis of amyloid-β protein (Aβ) is considered a crucial factor in the pathogenesis of Alzheimer's disease (AD). Hence, inhibiting Aβ fibrillogenesis is regarded as the primary therapeutic strategy for the prevention and treatment of AD. However, the development of effective inhibitors against Aβ fibrillo...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00441
更新日期:2019-01-16 00:00:00