Brain PET Imaging in the Cannabinoid System

Wong, Dean F.; Nandi, Ayon; Zaidi, Eram; Gean, Emily; Horti, Andrew G.; Фролов, Б. А.; George, Noble; Brašić, James Robert

doi:10.1016/b978-0-12-418677-4.00002-6

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…43,44 Study has shown that chronic alcohol exposure results in an increase in NMDA receptor number and function. 45 In this work, we investigated the effects of alcohol on cellular release of DA, 5-HT, Asp, and Glu from PC-12 cells.…”

Section: Resultsmentioning

confidence: 99%

Microfluidic Platform with In-Chip Electrophoresis Coupled to Mass Spectrometry for Monitoring Neurochemical Release from Nerve Cells

Zhao

et al. 2016

Anal. Chem.

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Chemical stimulus-induced neurotransmitter release from neuronal cells is well documented. However, the dynamic changes in neurochemical release remain to be fully explored. In this work, a three-layered microfluidic chip was fabricated and evaluated for studying the dynamics of neurotransmitter release from PC-12 cells. The chip features integration of a nanoliter sized chamber for cell perfusion, pneumatic pressure valves for fluidic control, a microfluidic channel for electrophoretic separation, and a nanoelectrospray emitter for ionization in MS detection. Deploying this platform, a microchip electrophoresismass spectrometric method (MCE-MS) was developed to simultaneously quantify important neurotransmitters, including dopamine (DA), serotonin (5-HT), aspartic acid (Asp), and glutamic acid (Glu) without need for labeling or enrichment. Monitoring neurotransmitter release from PC-12 cells exposed to KCl (or alcohol) revealed that all the four neurotransmitters investigated were released. Two release patterns were observed, one for the two monoamine neurotransmitters (i.e. DA and 5-HT), and another for the two amino acid neurotransmitters. Release dynamics for the two monoamine neurotransmitters was significantly different. The cells released DA most quickly and heavily in response to the stimulation. After exposure to the chemical stimulus for 4 min, DA level in the perfusate from the cells was 86% lower than that at the beginning. Very interestingly, the cells started to release 5-HT in large quantities when they stopped releasing DA. These results suggest that DA and 5-HT are packaged into different vesicle pools and they are mobilized differently in response to chemical stimuli. The microfluidic platform proposed is proven useful for monitoring cellular release in biological studies.

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Section: Resultsmentioning

confidence: 99%

Microfluidic Platform with In-Chip Electrophoresis Coupled to Mass Spectrometry for Monitoring Neurochemical Release from Nerve Cells

Zhao

et al. 2016

Anal. Chem.

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“…PET provides an invaluable tool to determine precisely the occupancy of each receptor affected by lumateperone. 21,46 The utilization of PET along with behavioral, cognitive, physiological, 90 and environmental measurements 14,89,91 provide a foundation for optimal clinical trials of schizophrenia, 10,15 and other neuropsychiatric disorders 92–100 and medical disorders. 101–103 PET will provide a tool to identify the effects of lumateperone on neurotransmitter systems already studied 21,46 and other possible pathways.…”

Section: Discussionmentioning

confidence: 99%

“…101–103 PET will provide a tool to identify the effects of lumateperone on neurotransmitter systems already studied 21,46 and other possible pathways. 92,100 Comprehensive multi-modal investigations by teams of experts around the world will facilitate the identification of biomarkers for clinical phenotypes of schizophrenia 104 to provide clinicians with the foundations to apply precision medicine to individuals with schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

The role of lumateperone in the treatment of schizophrenia

Syed

Brašić

2021

Therapeutic Advances in Psychopharmacology

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Schizophrenia is a devastating mental disorder resulting in marked morbidity and mortality despite the optimal use of all currently available interventions. For this reason, the release of lumateperone (CaptylaR), also known as ITI-007, an orally administered, atypical antipsychotic provided a welcome novel tool for clinicians to utilize precision medicine to tailor an optimal treatment plan to the specific needs of each person with schizophrenia. To generate a foundation for clinicians to assess the risks and benefits of lumateperone in relation to other interventions for schizophrenia, we conducted a search of items for ‘ITI-007’ and ‘lumateperone’ on PubMed, ScienceDirect, Web of Science, Google Scholar, and www.clinicaltrials.gov . We present a critical evaluation of the limited information about lumateperone for schizophrenia, its use approved by the US Food and Drug Administration. Lumateperone merits consideration for patients with treatment-resistant schizophrenia and for patients with schizophrenia who are vulnerable to developing metabolic dysfunction and movement disorders. On the other hand, lumateperone should not be used for (a) women who are pregnant or breastfeeding, children, adolescents, and elderly patients with dementia-related psychosis, (b) patients who are at risk for cerebrovascular diseases, (c) patients who use inducers and moderate or strong inhibitors of the cytochrome P450-3A4 (CYP3A4) isozyme, and (d) patients who use alcohol and other sedating agents. Clinical trials from multiple centers without financial conflicts of interest to market lumateperone are needed to directly compare and contrast lumateperone and other antipsychotic agents to generate trustworthy evidence to be assessed objectively by clinicians treating patients with schizophrenia. Future investigations will provide the foundations to identify the evidence for comprehensive evaluations of the role of lumateperone in the treatment of people with schizophrenia and other conditions.

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Molecular imaging of autism spectrum disorder

Hwang

Mohamed

Brašić

2017

International Review of Psychiatry

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Autism spectrum disorder (ASD) is a condition with onset in early childhood characterized by marked deficits in interpersonal interactions and communication and by a restricted and repetitive range of interests and activities. This review points out key recent findings utilizing molecular imaging including magnetic resonance spectroscopy (MRS) and nuclear neuroimaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). MRS indicates an excitatory/inhibitory imbalance in high-functioning autism. Dysfunction of neurotransmitter and glucose metabolism has been demonstrated by PET and SPECT. Levels of serotonin synthesis in typically developing children are approximately twice those of adults; after the age of 5 years, levels decrease to those of adults. In contrast, levels of serotonin synthesis of children with ASD increase between ages 2 and 15 to 1.5-times adult values. The dopamine transporter is increased in the orbitofrontal cortex of men with ASD. The serotonin transporter is reduced in the brains of children, adolescents, and adults with ASD. Reduced serotonin receptors in the thalamus of adults with ASD are associated with communication difficulties. Glucose metabolism is reduced in the brains of people with ASD. Molecular imaging will provide the preliminary data for promising therapeutic interventions.

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Brain PET Imaging in the Cannabinoid System

Cited by 3 publications

References 41 publications

Microfluidic Platform with In-Chip Electrophoresis Coupled to Mass Spectrometry for Monitoring Neurochemical Release from Nerve Cells

Microfluidic Platform with In-Chip Electrophoresis Coupled to Mass Spectrometry for Monitoring Neurochemical Release from Nerve Cells

The role of lumateperone in the treatment of schizophrenia

Molecular imaging of autism spectrum disorder

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