Article
Medicine, Research & Experimental
Alba Tristan-Noguero, Irene Fernandez-Carasa, Carles Calatayud, Cristina Bermejo-Casadesus, Meritxell Pons-Espinal, Arianna Colini Baldeschi, Leticia Campa, Francesc Artigas, Analia Bortolozzi, Rosario Domingo-Jimenez, Salvador Ibanez, Merce Pineda, Rafael Artuch, Angel Raya, Angels Garcia-Cazorla, Antonella Consiglio
Summary: This study used induced pluripotent stem cells (iPSCs) to generate dopaminergic neurons (DAn) from patients with tyrosine hydroxylase deficiency (THD) and compared them with control-DAn. THD iPSC-DAn showed lower levels of dopamine metabolites and reduced TH expression compared to controls. Additionally, THD iPSC-DAn displayed abnormal morphology and neuronal defects, which were rescued by L-Dopa treatment only in the milder form of THD (THD-A). Treatment at the stage of neuronal precursors could prevent the alterations in the severe form of THD (THD-B). This iPSC-based model recapitulates THD disease phenotypes and response to treatment.
EMBO MOLECULAR MEDICINE
(2023)
Article
Nanoscience & Nanotechnology
Qi Shang, Ling Zhang, Chan Chen, Weikang Tang, Mengqi Han, Qinfei Chen, Wenbin Liu
Summary: This study developed a nanozyme based on ethylenediaminetetraacetic acid (EDTA)-Fe2+ complex decorated Fe3O4 magnetic nanoparticles for biomimetic synthesis of L-DOPA. The nanozyme exhibited high catalytic performance, good reusability, and potential applications in the low-cost and high-efficiency production of L-DOPA.
ACS APPLIED NANO MATERIALS
(2022)
Review
Health Care Sciences & Services
Gyrid Nygaard, Peter D. Szigetvari, Ann Kari Grindheim, Peter Ruoff, Aurora Martinez, Jan Haavik, Rune Kleppe, Marte Flydal
Summary: Dopa-responsive dystonia (DRD) is a rare movement disorder linked to defective dopamine synthesis, mainly associated with mutations in the GCH1 gene. However, some patients do not respond well to L-DOPA treatment, especially in severe cases of TH deficiency. This highlights the need for more effective and personalized treatment options.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Dong Du, Yingli Su, Qi Shang, Chan Chen, Weikang Tang, Ling Zhang, Haisheng Ren, Wenbin Liu
Summary: This study developed a biomimetic system for the production of L-DOPA from tyrosine with high efficiency and selectivity. By using tyrosine as substrate and a catalyst to simulate the active center of tyrosine hydroxylase, L-DOPA was successfully synthesized under optimized process parameters.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Guang-Wen Li, Ji Li, Xiao-Yan Feng, Hui Chen, Ye Chen, Jing-Hua Liu, Yue Zhang, Feng Hong, Jin-Xia Zhu
Summary: Pancreatic beta cells can synthesize dopamine by taking L-dihydroxyphenylalanine, while pancreatic acinar cells synthesize L-dihydroxyphenylalanine, not dopamine. Both dopamine and L-dihydroxyphenylalanine are released into the pancreatic duct and regulated by the vagal cholinergic pathway.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemical Research Methods
Yinbiao Xu, Youran Li, Zhiyong Wu, Yiming Lu, Guanjun Tao, Liang Zhang, Zhongyang Ding, Guiyang Shi
Summary: This study successfully enhanced the production of L-DOPA through a modular engineering strategy. Firstly, the catalytic efficiency of tyrosine hydroxylase was improved by enhancing its affinity for tetrahydrobiopterin. Secondly, the supply of tetrahydrobiopterin was increased through gene expression manipulation, oxygen transport facilitation, and regeneration. Finally, the yield of L-tyrosine was significantly increased by manipulating a specific spliced transcript. The engineered strain achieved high yields of L-DOPA in both shake flask and bioreactor, showing great potential for microbial production of L-DOPA and downstream pharmaceuticals.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Qi Shang, Ling Zhang, Chan Chen, Weikang Tang, Mengqi Han, Qinfei Chen, Wenbin Liu
Summary: A nanozyme was developed for biomimetic synthesis of L-DOPA by mimicking natural tyrosine hydroxylase. It exhibited superparamagnetic characteristics and wide light response range. The nanozyme demonstrated high stability and reusability, and might provide a promising insight to produce L-DOPA.
Article
Biochemistry & Molecular Biology
Matheus C. Bianchini, Luiz F. W. Soares, Joao M. F. M. Sousa, Bruna P. Ramborger, Mateus C. Gayer, Jessika C. Bridi, Rafael Roehrs, Simone Pinton, Michael Aschner, Daiana S. Avila, Robson L. Puntel
Summary: This study found that exposure to methylmercury in fruit flies led to reduced survival rate, decreased levels of dopamine and octopamine, and changes in behavior. These effects were associated with inhibition of acetylcholinesterase and tyrosine hydroxylase, increased oxidative stress, and altered glutathione-S-transferase activity.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Jael R. Neyra Recky, Mariana P. Serrano, M. Laura Dantola, Carolina Lorente
Summary: Tyrosine, an amino acid, plays a crucial role in physiological events, and its oxidation can have both beneficial and detrimental effects on biological systems. The degradation of tyrosine often begins with the loss of an electron in the presence of an electron acceptor, and DOPA is identified as a key product in this process, showing antioxidant properties.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Chemistry, Analytical
Pin-Chuan Chen, Kuan-Han Chen, Chun-Yi Lin, Yi-Chun Yeh
Summary: The study developed a low-cost, user-friendly on-site detection system for accurately determining the ratio of L-DOPA to L-tyrosine, essential for clinical diagnosis of TH deficiency. Multiple experiments demonstrated that the system can efficiently and rapidly quantify L-DOPA, L-tyrosine, and creatinine even in complex bio-matrix, showing high reliability and repeatability.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Chemistry, Analytical
Chia-Wen Chang, Yu-Hsuan Lin, Cheng-Han Tsai, Sivasankar Kulandaivel, Yi-Chun Yeh
Summary: A novel heat-stable enzyme was developed for a protein-and cell-based biosensor, enabling the detection of L-DOPA for the first time. The detection of L-DOPA was achieved through a red fluorescent signal within 30 minutes. Furthermore, a sequential analysis method using dual-fluorescent signals was developed for the sensitive detection of dopamine and L-DOPA coexistence, allowing for monitoring of the therapy for Parkinson's disease patients treated with L-DOPA.
ANALYTICA CHIMICA ACTA
(2022)
Article
Neurosciences
Silas A. Buck, Briana R. De Miranda, Ryan W. Logan, Kenneth N. Fish, J. Timothy Greenamyre, Zachary Freyberg
Summary: The study found that DA neurons expressing VGLUT2 in the VTA/SNc exhibit higher resilience to rotenone-induced neurodegeneration, with an increase in VGLUT2 expression in response to rotenone. Dopaminergic terminals with VGLUT2 expression show greater protection throughout the striatum.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Yuxiao Yao, Diego Baronio, Yu-Chia Chen, Congyu Jin, Pertti Panula
Summary: This study found that the absence of the hrh1 gene in zebrafish leads to deficits in the dopaminergic and hypocretin systems during early development, but these deficits are compensated for in adulthood. However, adult fish exhibit impaired sociability and anxious-like behavior, along with downregulation of choline O-acetyltransferase and LIM homeodomain transcription factor Islet1.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Agronomy
Long-Ji Ze, Pei Wang, Ying-Chuan Peng, Lin Jin, Guo-Qing Li
Summary: The study revealed that TH and DDC play crucial roles in larval and adult cuticle tanning and development in 28-spotted potato ladybird, suggesting that dopa- and dopamine-originated pigments are essential for larval and adult feeding behavior and the molting process during emergence.
PEST MANAGEMENT SCIENCE
(2022)
Article
Neurosciences
Aaron E. Miller, Atul P. Daiwile, Jean Lud Cadet
Summary: This study found sex differences in dopamine metabolism in a methamphetamine addiction animal model, with the majority of differences observed in the mesocorticolimbic dopaminergic system.
NEUROTOXICITY RESEARCH
(2022)
Article
Neurosciences
Kevin M. Manz, Lillian J. Brady, Erin S. Calipari, Brad A. Grueter
Summary: This study reveals that histamine (HA) can modulate microcircuit motifs controlled by parvalbumin-expressing fast-spiking interneurons (PV-INs) and tonically active cholinergic interneurons (CINs) in the nucleus accumbens (NAc) shell through different receptor subtypes, providing critical insight into the modulatory potential of HA in the brain.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Neurosciences
Max E. Joffe, James Maksymetz, Joseph R. Luschinger, Shalini Dogra, Anthony S. Ferranti, Deborah J. Luessen, Isabel M. Gallinger, Zixiu Xiang, Hannah Branthwaite, Patrick R. Melugin, Kellie M. Williford, Samuel W. Centanni, Brenda C. Shields, Craig W. Lindsley, Erin S. Calipari, Cody A. Siciliano, Colleen M. Niswender, Michael R. Tadross, Danny G. Winder, P. Jeffrey Conn
Summary: Inhibitory interneurons play a role in regulating prefrontal cortex activity. The activation of mGlu(5) receptors facilitates long-term potentiation at synapses onto somatostatin-expressing interneurons in mice. This plasticity is recruited during acute restraint stress and is necessary for stress-induced changes to PFC physiology and related behaviors. SST-IN microcircuits may be promising therapeutic targets for stress-induced psychiatric diseases.
Article
Behavioral Sciences
Jordyn M. Wilcox, David C. Consoli, Krista C. Paffenroth, Brittany D. Spitznagel, Erin S. Calipari, Aaron B. Bowman, Fiona E. Harrison
Summary: This study investigates the differential effects of manganese exposure on wild-type and mutant mice in terms of behavioral tasks and dopamine dynamics. The results show that high manganese diet induces hyperactivity in young female wild-type mice and decreases the expression of tyrosine hydroxylase. However, there are no significant effects of manganese diet in aged mice. This study suggests that manganese exposure may play a role in stabilizing dopaminergic dysfunction in early Huntington's disease.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2022)
Article
Geriatrics & Gerontology
Michael F. Salvatore, Ella A. Kasanga, D. Parker Kelley, Katy E. Venable, Tamara R. McInnis, Mark A. Cantu, Jennifer Terrebonne, Kathryn Lanza, Samantha M. Meadows, Ashley Centner, Christopher Bishop, Donald K. Ingram
Summary: This study investigates the contributions of nigral and striatal dopamine mechanisms to aging-related parkinsonian signs. Calorie restriction can alleviate parkinsonian signs, and this effect can be maintained in advanced age. Moreover, changes in nigral dopamine signaling may modulate certain parameters of locomotor activity autonomously from striatal dopamine signaling.
Article
Neurosciences
Michael F. Salvatore, Isabel Soto, Ella A. Kasanga, Rachael James, Marla K. Shifflet, Kirby Doshier, Joel T. Little, Joshia John, Helene M. Alphonso, J. Thomas Cunningham, Vicki A. Nejtek
Summary: By studying cardiovascular parameters in Parkinson's disease patients and rat models, we can evaluate the impact of aerobic exercise on specific motor or cognitive functions. A moderate intensity exercise regimen is suitable for early-stage Parkinson's disease patients.
JOURNAL OF PARKINSONS DISEASE
(2022)
Article
Neurosciences
Jordan A. Brown, Nicholas Petersen, Samuel W. Centanni, Allie Y. Jin, Hye Jean Yoon, Stephanie A. Cajigas, Michelle N. Bedenbaugh, Joseph R. Luchsinger, Sachin Patel, Erin S. Calipari, Richard B. Simerly, Danny G. Winder
Summary: Alpha(2a)-adrenergic receptor agonists have the potential to be therapeutics for substance use disorder due to their ability to regulate stress system engagement. However, recent findings suggest that postsynaptic alpha(2a)-ARs are necessary for stress-induced reinstatement of drug-seeking behavior. In this study, the researchers utilized FosTRAP mice to identify a population of cells in the bed nucleus of the stria terminalis that are activated by the partial agonist guanfacine. They found that these cells, called Guansembles, differ from cells activated by restraint stress. Guanfacine inhibited cAMP-dependent signaling in Guansembles, while chronic restraint stress increased signaling. Additionally, the researchers found that active coping events during restraint stress and exposure to unexpected shocks were associated with Guansemble recruitment. Using viral tracing, they identified a network of regions involved in stress and homeostatic functions that project to the BNST Guansembles. Activation of Guansembles also produced alterations in behavior consistent with task-specific anxiety-like behavior. Overall, this study provides important insights into the role of alpha(2a)-AR signaling and stress in regulating drug-seeking behavior.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alyssa M. West, Katherine M. Holleran, Sara R. Jones
Summary: The serotonin and kappa opioid receptor (KOR) systems play important roles in disorders of negative affect. In this study, the researchers investigated the effects of KOR activation and serotonin reuptake inhibition on serotonin transmission in the substantia nigra pars reticulata (SNr). They found that KOR activation reduced serotonin release and uptake, while serotonin reuptake inhibition increased serotonin release and slowed reuptake. The researchers also demonstrated that short-term activation of KOR altered serotonin responses to reuptake inhibition. These findings highlight the complex interactions between KORs and serotonin in regulating negative affect, and suggest that the KOR system may be a promising target for treating disorders such as anxiety and depression alongside traditional antidepressant treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Emma G. Follman, Maxime Chevee, Courtney J. Kim, Amy R. Johnson, Jennifer Tat, Michael Z. Leonard, Erin S. Calipari
Summary: This study investigates the influence of operant conditioning on the reproducibility of operant responses in mice. The findings suggest that signaling reinforcer delivery with a cue can increase learning rates but may result in fast succession of lever presses instead of discrete bouts. The selection of appropriate parameters is crucial to promote reproducible action execution in behavioral training.
PSYCHOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Brooke A. Christensen, Erin S. Calipari
Summary: The study reveals the distinct and differential mechanisms of methamphetamine enantiomers on dopamine and norepinephrine release, providing critical insights into the pharmacodynamic properties of this stimulant.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Neurosciences
Soren D. Emerson, Maxime Chevee, Philipp Mews, Erin S. Calipari
Summary: A large body of work has demonstrated the central role of cocaine-induced changes in transcriptional regulation in cocaine use disorder. This study shows that the pharmacodynamic properties of cocaine can change depending on an organism's previous drug-exposure history. The researchers used RNA sequencing to characterize how acute cocaine exposure affects gene expression in different brain regions, and found that the gene expression patterns were altered in mice with a history of cocaine self-administration and long-term withdrawal.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Alexis N. Jameson, Justin K. Siemann, James Melchior, Erin S. Calipari, Douglas G. McMahon, Brad A. Grueter
Summary: The brain is sensitive to changes in the circadian photoperiod and it affects animal behavior in order to adapt to the environment. Women are more prone to affective disorders than men, and longer photoperiods have a stronger impact on dopamine signaling in females, potentially explaining the seasonal differences between genders.
Article
Pharmacology & Pharmacy
Anushree N. Karkhanis, Alyssa M. West, Sara R. Jones
Summary: The nucleus accumbens (NAc) core plays a role in regulating stress and shaping reward seeking behaviours. The activation of kappa opioid receptor (KOR) inhibits dopamine release and transmission, and this impact is regionally specific in the NAc shell. The inhibition of dopamine release by KOR is greater in the caudal compared to the rostral subregion of NAc core, suggesting a differential regulation along the rostro-caudal axis.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Neurosciences
Katherine R. Meckel, Sierra S. Simpson, Arthur Godino, Emily G. Peck, Jonathon P. Sens, Michael Z. Leonard, Olivier George, Erin S. Calipari, Rebecca S. Hofford, Drew D. Kiraly
Summary: Cocaine use disorder is a public health crisis and there are currently no FDA-approved medications for its treatment. Research has shown the important role of the gut microbiome and its metabolites in modulating drug-seeking behaviors, but their impact on relapse after prolonged abstinence is unknown. This study reveals that depletion of the gut microbiome enhances cocaine-seeking behavior, while restoration of bacterially-derived metabolites reverses this effect, suggesting the potential of the microbiome as a target for translational research.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Cell Biology
Munir Gunes Kutlu, Jennifer Tat, Brooke A. Christensen, Jennifer E. Zachry, Erin S. Calipari
Summary: Dopamine release in the nucleus accumbens is causally linked to adaptive aversive learning and its dysregulation is a core phenotype in anxiety and stress disorders. The study recorded NAc core dopamine during a task where mice learn to discriminate between cues signaling footshock presentation and footshock omission. It was found that dopamine release is evoked by footshock omission and this signal plays a role in discrimination learning.
Meeting Abstract
Substance Abuse
Carole Morel, Sarah E. Montgomery, Long Li, Stacy M. Ku, Barbara Juarez, Meghan E. Flannigan, Erin S. Calipari, Jessica J. Walsh, Scott J. Russo, Allyson K. Friedman, Ming-Hu Han