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JOURNAL ARTICLE
Roine El-Habta, Sara Af Bjerkén, Ana Virel
OBJECTIVES: Current treatments for Parkinson's disease using pharmacological approaches alleviate motor symptoms but do not prevent neuronal loss or dysregulation of dopamine neurotransmission. In this article, we have explored the molecular mechanisms underlying the neuroprotective effect of the antioxidant N -acetylcysteine (NAC) on the damaged dopamine system. METHODS: SH-SY5Y cells were differentiated towards a dopaminergic phenotype and exposed to 6-hydroxydopamine (6-OHDA) to establish an in vitro model of Parkinson's disease...
March 18, 2024: Neurological Research
#22
JOURNAL ARTICLE
Dianmei Yu, Haiyan Wang, Yiwen Zhai, Zhixiang Lei, Minglu Sun, Si Chen, Panfeng Yin, Xianchun Wang
BACKGROUND: Parkinson's disease (PD) is characterized by death of dopaminergic neurons leading to dopamine deficiency, excessive α-synuclein facilitating Lewy body formation, etc. Latroeggtoxin-VI (LETX-VI), a proteinaceous neurotoxin discovered from the eggs of spider L. tredecimguttatus, was previously found to promote the synthesis and release of PC12 cells, showing a great potential as a drug candidate for PD. However, the relevant mechanisms have not been understood completely...
March 16, 2024: Biological Research
#23
JOURNAL ARTICLE
Sherilyn Junelle Recinto, Shobina Premachandran, Sriparna Mukherjee, Alexis Allot, Adam MacDonald, Moein Yaqubi, Samantha Gruenheid, Louis-Eric Trudeau, Jo Anne Stratton
The enteric nervous system (ENS) comprises a complex network of neurons whereby a subset appears to be dopaminergic although the characteristics, roles, and implications in disease are less understood. Most investigations relating to enteric dopamine (DA) neurons rely on immunoreactivity to tyrosine hydroxylase (TH)-the rate-limiting enzyme in the production of DA. However, TH immunoreactivity is likely to provide an incomplete picture. This study herein provides a comprehensive characterization of DA neurons in the gut using a reporter mouse line, expressing a fluorescent protein (tdTomato) under control of the DA transporter (DAT) promoter...
March 15, 2024: European Journal of Neuroscience
#24
JOURNAL ARTICLE
Avelina Petri, Abigail Sullivan, Kristen Allen, Benjamin D Sachs
Dopaminergic neurotransmission has emerged as a critical determinant of stress susceptibility and resilience. Although the dopamine transporter (DAT) is known to play a key role in maintaining dopamine (DA) homeostasis, its importance for the regulation of stress susceptibility remains largely unknown. Indeed, while numerous studies have examined the neurochemical and behavioral consequences of genetic loss of DAT, very few have compared responses to stress in wild-type and DAT-knockout (KO) animals. The current study compared the responses of male and female WT and DAT-KO mice to a model of sub-chronic stress...
2024: Frontiers in Molecular Neuroscience
#25
JOURNAL ARTICLE
Rong Chen
The dopamine transporter (DAT) is a key site of action for cocaine and amphetamines. Dysfunctional DAT is associated with aberrant synaptic dopamine transmission and enhanced drug-seeking and taking behavior. Studies in cultured cells and ex vivo suggest that DAT function is sensitive to membrane cholesterol content. Although it is largely unknown whether psychostimulants alter cholesterol metabolism in the brain, emerging evidence indicates that peripheral cholesterol metabolism is altered in patients with psychostimulant use disorder and circulating cholesterol levels are associated with vulnerability to relapse...
2024: Advances in Pharmacology
#26
JOURNAL ARTICLE
Melinda Hersey, Gianluigi Tanda
Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has been explored for other potential therapeutic uses. Indeed, it has shown promise as a therapy for cognitive disfunction resulting from neurologic disorders like ADHD, and as a smart drug in non-medical settings. The mechanism(s) of actions underlying the therapeutic efficacy of this agent remains largely elusive. Modafinil is known to inhibit the dopamine transporter, thus decreasing dopamine reuptake following neuronal release, an effect shared by addictive psychostimulants...
2024: Advances in Pharmacology
#27
REVIEW
Emily J Miller, Habibeh Khoshbouei
Methamphetamine (METH) regulation of the dopamine transporter (DAT) and central nervous system (CNS) dopamine transmission have been extensively studied. However, our understanding of how METH influences neuroimmune communication and innate and adaptive immunity is still developing. Recent studies have shed light on the bidirectional communication between the CNS and the peripheral immune system. They have established a link between CNS dopamine levels, dopamine neuronal activity, and peripheral immunity. Akin to dopamine neurons in the CNS, a majority of peripheral immune cells also express DAT, implying that in addition to their effect in the CNS, DAT ligands such as methamphetamine may have a role in modulating peripheral immunity...
2024: Advances in Pharmacology
#28
JOURNAL ARTICLE
Hoa Tt Ha, SiYi Liu, Xuan Ta Nguyen, Linh K Vo, Nancy Cp Leong, Dat T Nguyen, Shivaranjani Balamurugan, Pei Yen Lim, YaJun Wu, Eunju Seong, Toan Q Nguyen, Jeongah Oh, Markus R Wenk, Amaury Cazenave-Gassiot, Zuhal Yapici, Wei-Yi Ong, Margit Burmeister, Long N Nguyen
Accumulation of sphingolipids, especially sphingosines, in the lysosomes is a key driver of several lysosomal storage diseases. The transport mechanism for sphingolipids from the lysosome remains unclear. Here, we identified SPNS1, which shares the highest homology to SPNS2 - a sphingosine-1-phosphate (S1P) transporter, functions as a transporter for lysolipids from the lysosome. We generated Spns1 knockout cells and mice and employed lipidomic and metabolomic approaches to reveal SPNS1 ligand identity. Global knockout of Spns1 caused embryonic lethality between E12...
March 7, 2024: JCI Insight
#29
JOURNAL ARTICLE
Melinda Hersey, Maddalena Mereu, Claire S Jones, Mattingly K Bartole, Andy Y Chen, Jianjing Cao, Takato Hiranita, Lauren E Chun, Jessica P Lopez, Jonathan L Katz, Amy Hauck Newman, Gianluigi Tanda
Psychostimulant use disorders (PSUD) are prevalent; however, no FDA-approved medications have been made available for treatment. Previous studies have shown that dual inhibitors of the dopamine transporter (DAT) and sigma receptors significantly reduce the behavioral/reinforcing effects of cocaine, which have been associated with stimulation of extracellular dopamine (DA) levels resulting from DAT inhibition. Here, we employ microdialysis and fast scan cyclic voltammetry (FSCV) procedures to investigate the effects of dual inhibitors of DAT and sigma receptors in combination with cocaine on nucleus accumbens shell (NAS) DA dynamics in naïve male Sprague Dawley rats...
March 5, 2024: European Journal of Neuroscience
#30
JOURNAL ARTICLE
Noritaka Wakasugi, Harumasa Takano, Mitsunari Abe, Nobukatsu Sawamoto, Toshiya Murai, Toshiki Mizuno, Teruyuki Matsuoka, Ryo Yamakuni, Hirooki Yabe, Hiroshi Matsuda, Takashi Hanakawa
BACKGROUND: Dopamine transporter single-photon emission computed tomography (DAT-SPECT) is a crucial tool for evaluating patients with Parkinson's disease (PD). However, its implication is limited by inter-site variability in large multisite clinical trials. To overcome the limitation, a conventional prospective correction method employs linear regression with phantom scanning, which is effective yet available only in a prospective manner. An alternative, although relatively underexplored, involves retrospective modeling using a statistical method known as "combatting batch effects when combining batches of gene expression microarray data" (ComBat)...
2024: Frontiers in Neurology
#31
JOURNAL ARTICLE
Jing Chen, Baoyu Chen, Danhua Zhao, Xiaotong Feng, Qi Wang, Yuan Li, Junyi Chen, Chaobo Bai, Xintong Guo, Xiaoyu He, Lin Zhang, Junliang Yuan
AIMS: To investigate the risk factors for early-onset psychosis in Parkinson's disease (PD) in a cohort of patients from the Parkinson's Progression Markers Initiative. METHODS: Longitudinal data on motor and non-motor features, dopamine transporter (DAT) imaging, and cerebrospinal fluid (CSF) measurements were collected. The survival probability of psychotic symptoms, potential risk factors for psychosis development over a 5-year follow-up period, and the performance of the prediction model were evaluated...
March 2024: CNS Neuroscience & Therapeutics
#32
JOURNAL ARTICLE
Liyu Cao, Chiara Palmisano, Xinyu Chen, Ioannis U Isaias, Barbara F Händel
OBJECTIVE: Both blinking and walking are altered in Parkinson's disease and both motor outputs have been shown to be linked in healthy subjects. Additionally, studies suggest an involvement of basal ganglia activity and striatal dopamine in blink generation. We investigated the role of the basal ganglia circuitry on spontaneous blinking and if this role is dependent on movement state and striatal dopamine. METHODS: We analysed subthalamic nucleus (STN) activity in seven chronically implanted patients for deep brain stimulation (DBS) with respect to blinks and movement state (resting state and unperturbed walking)...
February 19, 2024: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
#33
JOURNAL ARTICLE
Alev Ecevitoglu, Nicolette Meka, Renee A Rotolo, Gayle A Edelstein, Sonya Srinath, Kathryn R Beard, Carla Carratala-Ros, Rose E Presby, Jianjing Cao, Amarachi Okorom, Amy H Newman, Mercè Correa, John D Salamone
People with depression and other neuropsychiatric disorders can experience motivational dysfunctions such as fatigue and anergia, which involve reduced exertion of effort in goal-directed activity. To model effort-related motivational dysfunction, effort-based choice tasks can be used, in which rats can select between obtaining a preferred reinforcer by high exertion of effort vs. a low effort/less preferred option. Preclinical data indicate that dopamine transport (DAT) inhibitors can reverse pharmacologically-induced low-effort biases and increase selection of high-effort options in effort-based choice tasks...
March 1, 2024: Neuropsychopharmacology
#34
JOURNAL ARTICLE
Gisela Andrea Camacho-Hernandez, Adithya Gopinath, Amarachi V Okorom, Habibeh Khoshbouei, Amy Hauck Newman
The dopamine transporter (DAT) is one of the key regulators of dopamine (DA) signaling in the central nervous system (CNS) and in the periphery. Recent reports in a model of Parkinson's disease (PD) have shown that dopamine neuronal loss in the CNS impacts the expression of DAT in peripheral immune cells. The mechanism underlying this connection is still unclear but could be illuminated with sensitive and high-throughput detection of DAT-expressing immune cells in the circulation. Herein, we have developed fluorescently labeled ligands (FLL) that bind to surface-expressing DAT with high affinity and selectivity...
February 26, 2024: JACS Au
#35
JOURNAL ARTICLE
Francesco Biscarini, Fabio Pizza, Stefano Vandi, Alex Incensi, Elena Antelmi, Vincenzo Donadio, Raffaele Ferri, Rocco Liguori, Giuseppe Plazzi
BACKGROUND AND PURPOSE: This study compared the features of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and antidepressant-related REM sleep behaviour disorder (RBD) with the aim of highlighting markers that might distinguish the two entities. METHODS: The observational cohort study included RBD patients with and without antidepressant use (antiD+ and antiD- patients, respectively), without cognitive impairment and parkinsonism. Clinical features of RBD, subtle motor and non-motor symptoms of parkinsonism, sleep architecture, REM atonia index, dopamine transporter-single photon emission computed tomography (DAT-SPECT) and skin biopsies for the intraneuronal alpha-synuclein (α-syn), were evaluated in the baseline work-up...
February 26, 2024: European Journal of Neurology
#36
JOURNAL ARTICLE
Fabio Bellia, Antonio Girella, Eugenia Annunzi, Beatrice Benatti, Matteo Vismara, Alberto Priori, Fabiana Festucci, Federico Fanti, Dario Compagnone, Walter Adriani, Bernardo Dell'Osso, Claudio D'Addario
Obsessive Compulsive Disorder (OCD) is listed as one of the top 10 most disabling neuropsychiatric conditions in the world. The neurobiology of OCD has not been completely understood and efforts are needed in order to develop new treatments. Beside the classical neurotransmitter systems and signalling pathways implicated in OCD, the possible involvement of the endocannabinoid system (ECS) has emerged in pathophysiology of OCD. We report here selective downregulation of the genes coding for enzymes allowing the synthesis of the endocannabinoids...
February 26, 2024: Translational Psychiatry
#37
JOURNAL ARTICLE
Concetto Puzzo, Fabiana Festucci, Giuseppe Curcio, Antonella Gigantesco, Walter Adriani
Dopamine (DA) is mainly involved in locomotor activity, reward processes and maternal behaviors. Rats with KO gene for dopamine transporter (DAT) coding for a truncated DAT protein are in hyperdopaminergic conditions and develop stereotyped behaviors and hyperactivity. Our aim was to test the prior transgenerational modulation of wild and truncated allele as expressed in heterozygous DAT rats: specifically we addressed the possible sequelae due to genotype and gender of the ancestors, with regard to behavioral differences in F1 , F2 , F3 rats...
February 24, 2024: Behavioural Brain Research
#38
JOURNAL ARTICLE
Jie Liu, Jing Kang, Meihui Qi, Jie Tang, Yi Fang, Chunyi Liu, Jingjing Hong, Jiaojiao Zuo, Zhengping Chen
The dopamine transporter (DAT) is closely related to a variety of neurological disorders including Parkinson's disease (PD) and other neurodegenerative diseases. In vivo imaging of DAT with radio-labelled tracers has become a powerful technique in related disorders. The radioiodine-labelled tropane derivative [123 I]FP-CIT ([123 I]1a) is widely used in clinical single photon emission computed tomography (SPECT) imaging as a DAT imaging agent. To develop more metabolically stable DAT radioligands for accurate imaging, this work compared two novel deuterated tropane derivatives ([131 I]1c-d) with non-deuterated tropane derivatives ([131 I]1a-b)...
February 24, 2024: Bioorganic & Medicinal Chemistry Letters
#39
Daniel G Calame, Jovi Huixin Wong, Puravi Panda, Dat Tuan Nguyen, Nancy C P Leong, Riccardo Sangermano, Sohil G Patankar, Mohamed Abdel-Hamid, Lama AlAbdi, Sylvia Safwat, Kyle P Flannery, Zain Dardas, Jawid M Fatih, Chaya Murali, Varun Kannan, Timothy E Lotze, Isabella Herman, Farah Ammouri, Brianna Rezich, Stephanie Efthymiou, Shahryar Alavi, David Murphy, Zahra Firoozfar, Mahya Ebrahimi Nasab, Amir Bahreini, Majid Ghasemi, Nourelhoda A Haridy, Hamid Reza Goldouzi, Fatemeh Eghbal, Ehsan Ghayoor Karimiani, Varunvenkat M Srinivasan, Vykuntaraju K Gowda, Haowei Du, Shalini N Jhangiani, Zeynep Coban-Akdemir, Dana Marafi, Lance Rodan, Sedat Isikay, Jill A Rosenfeld, Subhadra Ramanathan, Michael Staton, Kerby C Oberg, Robin D Clark, Catharina Wenman, Sam Loughlin, Ramy Saad, Tazeen Ashraf, Alison Male, Shereen Tadros, Reza Boostani, Ghada M H Abdel-Salam, Maha Zaki, Ebtesam Abdalla, M Chiara Manzini, Davut Pehlivan, Jennifer E Posey, Richard A Gibbs, Henry Houlden, Fowzan S Alkuraya, Kinga Bujakowska, Reza Maroofian, James R Lupski, Long Nam Nguyen
FLVCR1 encodes Feline leukemia virus subgroup C receptor 1 (FLVCR1), a solute carrier (SLC) transporter within the Major Facilitator Superfamily. FLVCR1 is a widely expressed transmembrane protein with plasma membrane and mitochondrial isoforms implicated in heme, choline, and ethanolamine transport. While Flvcr1 knockout mice die in utero with skeletal malformations and defective erythropoiesis reminiscent of Diamond-Blackfan anemia, rare biallelic pathogenic FLVCR1 variants are linked to childhood or adult-onset neurodegeneration of the retina, spinal cord, and peripheral nervous system...
February 13, 2024: medRxiv
#40
JOURNAL ARTICLE
Tomoya Kawazoe, Keizo Sugaya, Yasuhiro Nakata, Masato Okitsu, Kazushi Takahashi
INTRODUCTION: The present study characterized the degeneration of nigrostriatal dopaminergic neurons in the early stages of parkinsonian disorders using integrative neuroimaging analysis with neuromelanin-sensitive MRI and 123 I-FP-CIT dopamine transporter (DAT) SPECT. METHODS: Thirty-one, 30, and 29 patients with progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) with abnormal specific binding ratio (SBR) in either hemisphere (mean ± 2SD), and parkinsonism-predominant multiple system atrophy (MSA-P), respectively, were enrolled...
2024: Clinical parkinsonism & related disorders
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