Article
Neurosciences
Keita Sugiyama, Mahomi Kuroiwa, Takahide Shuto, Yoshinori N. Ohnishi, Yukie Kawahara, Yuta Miyamoto, Takaichi Fukuda, Akinori Nishi
Summary: The striatum, the main structure of the basal ganglia, is subdivided into seven subregions with distinct roles in motor and emotional functions. Dopamine D1 receptor signaling is region-specifically regulated in the striatum, with aberrant activation in the IC associated with L-DOPA-induced dyskinesia. Future research focusing on D1 receptor signaling in the IC may lead to novel therapeutics for LID.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Clinical Neurology
Yong Hu, Thong C. Ma, Stephanie L. Alberico, Yunmin Ding, Lingjing Jin, Un Jung Kang
Summary: This study aimed to determine whether direct modulation of SNr GABAergic neurons and SNr projections to the PPN can regulate PD symptoms and levodopa-induced dyskinesia (LID). The results showed that suppressing SNr neuron activity improved akinesia, while increasing SNr neuronal activity significantly reduced LID. The projections from SNr to PPN likely mediate the antidyskinetic effect of increasing SNr neuronal activity.
MOVEMENT DISORDERS
(2023)
Article
Neurosciences
Jiazhi Chen, Qiang Wang, Nanxiang Li, Shujie Huang, Min Li, Junbin Cai, Yuzheng Wang, Huantao Wen, Siyuan Lv, Ning Wang, Jinyan Wang, Fei Luo, Wangming Zhang
Summary: Excessive theta frequency oscillation and synchronization in the basal ganglia have been reported in elderly parkinsonian patients and LID animal models, especially during the off L-dopa state. Chronic L-dopa usage increases theta synchronization and information flow between SNr and M1 in LID rats, with a directionality from SNr to M1. Theta oscillational activity in M1 may result from abnormal synchronous discharges in the BG and may participate in the induction of dyskinesia.
NEUROSCIENCE BULLETIN
(2021)
Article
Multidisciplinary Sciences
Esther Gramage, Jorge Saiz, Rosalia Fernandez-Calle, Yasmina B. Martin, Maria Uribarri, Marcel Ferrer-Alcon, Coral Barbas, Gonzalo Herradon
Summary: This study found that overexpression of PTN has a neuroprotective effect in a mouse model of Parkinson's Disease and identified potential lipid-related drug candidates for Parkinson's Disease.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Bok-Seok Kim, Taeik Jang, Sung-Eun Yoo, Jae Moon Lee, Eunhee Kim
Summary: The impairment of protein clearance mechanisms in dopaminergic neurons leads to the accumulation of alpha-synuclein, contributing to the pathogenesis of Parkinson's disease. Fas-associated factor 1 (FAF1) was found to disrupt alpha-synuclein clearance through the autophagy-lysosome pathway, indicating a novel role as a negative regulator of autophagic alpha-synuclein clearance. This disturbance ultimately leads to alpha-synuclein accumulation and autophagy dysregulation in PD model mice.
Article
Neurosciences
Kathryn Lanza, Ashley Centner, Michael Coyle, Isabella Del Priore, Fredric P. Manfredsson, Christopher Bishop
Summary: Inhibiting the upregulation of D3R in D1R cells with a miRNA strategy significantly attenuates the development of LID, without affecting the efficacy of L-DOPA or other locomotion. This highlights the dyskinesiogenic role of D3R within D1R cells in LID and suggests aberrant D1R-D3R interactions as potential targets for LID management.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Anatomy & Morphology
Kumiko Ogata, Fuko Kadono, Yasuharu Hirai, Ken-ichi Inoue, Masahiko Takada, Fuyuki Karube, Fumino Fujiyama
Summary: The striatum plays a crucial role in controlling voluntary behaviors and reinforcement learning. Two atypical zones, with imbalanced populations of D1R neurons and D2R neurons respectively, were identified in the caudal striatum. These imbalanced zones exhibit similar axonal projections and electrophysiological properties as other regions of the striatum.
FRONTIERS IN NEUROANATOMY
(2022)
Article
Pharmacology & Pharmacy
Libo Zhang, Shiqiu Meng, Wenjun Chen, Yun Chen, Enze Huang, Guipeng Zhang, Yisen Liang, Zengbo Ding, Yanxue Xue, Jie Shi, Yun Shi
Summary: Studies have shown that DBS of the substantia nigra pars reticulata (SNr) can facilitate extinction and prevent reinstatement of methamphetamine-induced conditioned place preference (CPP). High-frequency (HF) DBS has a positive effect on this process, while low-frequency (LF) DBS impairs extinction.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Merel Dagher, Katie A. Perrotta, Sara A. Erwin, Ayaka Hachisuka, Rahul Iyer, Sotiris C. Masmanidis, Hongyan Yang, Anne M. Andrews
Summary: Targeting neurons with light-driven opsins is a commonly used approach to study cell-specific responses. In this study, the activation of dopamine neurons resulted in the release of dopamine and serotonin in the striatum, suggesting a potential interaction between these two neurotransmitters.
ACS CHEMICAL NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Allen P. F. Chen, Lu Chen, Thomas A. Kim, Qiaojie Xiong
Summary: Dopamine plays a crucial role in controlling CNS function and its dysregulation can lead to various cognitive symptoms associated with neuropsychiatric diseases. Different brain areas have varying functions and roles for dopamine, suggesting potential differential dysregulation in different disease states.
Review
Biochemistry & Molecular Biology
Kathryn Lanza, Christopher Bishop
Summary: Parkinson's Disease (PD) and long-term L-DOPA treatment induce plasticity that contributes to L-DOPA-induced dyskinesia (LID), with the dopamine D3 receptor (D3R) emerging as a promising target in LID management due to its upregulation in LID. D3R undergoes dynamic changes in both PD and LID, and recent genetic and pharmacologic tools have helped clarify its role in LID.
Article
Biochemistry & Molecular Biology
Emanuela Paldino, Vincenza D'angelo, Mariangela Massaro Cenere, Ezia Guatteo, Simone Barattucci, Giorgia Migliorato, Nicola Berretta, Olaf Riess, Giuseppe Sancesario, Nicola Biagio Mercuri, Francesca Romana Fusco
Summary: This study used immunohistochemical studies to investigate neuropathological changes in a rat transgenic model of Parkinson's disease (PD). It found that in the advanced stages of the disease, there was neuronal loss in the dorsolateral part of the striatum, along with a dramatic loss of parvalbumin interneurons. A marked decrease in the neurotrophic factor called glial-derived neurotrophic factor (GDNF) was also observed in the striatum and substantia nigra of these animals. This confirms the involvement of the striatum in PD pathophysiology and the importance of GDNF in maintaining the health of the substantia nigra.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Andrea Slezia, Panna Hegedus, Evgeniia Rusina, Katalin Lengyel, Nicola Solari, Attila Kaszas, Diana Balazsfi, Boris Botzanowski, Emma Acerbo, Florian Missey, Adam Williamson, Balazs Hangya
Summary: Studying animal models allows us to better understand the mechanisms of Parkinson's disease. However, current models mainly focus on late-stage symptoms, leaving a gap in our knowledge of early-stage changes. In this study, a graded-dose unilateral 6-OHDA model was established in mice, and the behavioral, neuronal, and ultrastructural features were analyzed within the first two weeks of lesion induction. The results showed that mild degeneration of dopaminergic neurons can lead to motor deficits shortly after striatal lesions, suggesting that this model can be used to study the early stages of Parkinson's disease in mice.
SCIENTIFIC REPORTS
(2023)
Article
Neurosciences
M. S. Shahpari, M. R. N. Namavar, L. K. D. Kamali Dolatabadi, H. A. Aligholi, M. E. Emamghoreishi
Summary: The study showed that SNpr plays a crucial role in seizure propagation, with differences in diameter and cell numbers observed between early and late-phase kindled groups. These findings indicate that SNpr is an important structure involved in the processes of epileptogenesis.
NEUROSCIENCE LETTERS
(2021)
Article
Clinical Neurology
Shinichi Matsumoto, Hidetaka Koizumi, Hideki Shimazu, Ryuji Kaji, Satoshi Goto
Summary: This study found that dual pharmacotherapy with L-DOPA and CPZ has a therapeutic effect on blepharospasm, suggesting that attenuating dystonia symptoms through dopaminergic modulation and increasing striatal D1-signals is possible. These findings are important for understanding the pathogenesis of dystonia.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemical Research Methods
Cristian Camuto, Angelica Guglielmelli, Fabio De-Giorgio, Xavier de la Torre, Monica Mazzarino, Matteo Marti, Francesco Botre
Summary: This study investigated the in vitro phase I metabolism of Mexedrone, revealing that the primary metabolic reactions involved hydroxylation and N- and O-dealkylation. The key CYP450 isoform responsible for these reactions was found to be CYP2C19. The most appropriate markers of intake were identified as unchanged Mexedrone and hydroxylated metabolites.
DRUG TESTING AND ANALYSIS
(2022)
Article
Law
S. Pesavento, S. Bilel, M. Murari, R. Gottardo, R. Arfe, M. Tirri, A. Panato, F. Tagliaro, M. Marti
Summary: This study investigates the use of zebrafish larvae as an animal model to study the effects and metabolism of fentanyl, a dangerous new psychoactive substance. The results show that the effects of fentanyl on zebrafish larvae are consistent with those observed in mice, and the metabolic pathways of fentanyl are identified in both models. This suggests that zebrafish larvae could be a suitable tool for rapid screening of new drugs and new psychoactive substances.
MEDICINE SCIENCE AND THE LAW
(2022)
Article
Biochemistry & Molecular Biology
Monia Lenzi, Sofia Gasperini, Veronica Cocchi, Micaela Tirri, Matteo Marti, Patrizia Hrelia
Summary: This study evaluated the genotoxic potential of the novel psychoactive substance 4,4'-DMAR using in vitro mammalian cell micronucleus test (MNvit). The results showed opposite behaviors of the cis- and trans- racemates in micronuclei frequency, highlighting the importance of testing single NPSs that show even small differences in structure or conformation. Consuming both racemates was found to magnify the genotoxic effect, emphasizing the unpredictability of illicit drug composition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Sabrine Bilel, Joaquim Azevedo Neto, Raffaella Arfe, Micaela Tirri, Rosa Maria Gaudio, Anna Fantinati, Tatiana Bernardi, Federica Boccuto, Beatrice Marchetti, Giorgia Corli, Giovanni Serpelloni, Fabio De-Giorgio, Davide Malfacini, Claudio Trapella, Girolamo Calo', Matteo Marti
Summary: This study investigates the pharmacodynamic profiles of three fentanyl analogues and reveals their high potency and selectivity, significant effects on mechanical and thermal analgesia, as well as impairments on motor and cardiorespiratory parameters.
Article
Biochemistry & Molecular Biology
Micaela Tirri, Raffaella Arfe, Sabrine Bilel, Giorgia Corli, Beatrice Marchetti, Anna Fantinati, Fabrizio Vincenzi, Fabio De-Giorgio, Cristian Camuto, Monica Mazzarino, Mario Barbieri, Rosa Maria Gaudio, Katia Varani, Pier Andrea Borea, Francesco Botre, Matteo Marti
Summary: This study compared the pharmacodynamic activity of synthetic cannabinoids JWH-175 and JWH-018 in vitro and in vivo, and evaluated the metabolic profile of JWH-175. The results showed that JWH-175 is a less potent cannabinoid receptor agonist compared to JWH-018 and is rapidly converted to JWH-018 in vivo. This study provides important insights into the pharmacotoxicological profile of JWH-175 and emphasizes the importance of studying the in vivo metabolism of synthetic cannabinoids for clinical toxicology and forensic purposes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Valerio Benedetti, Federica Banfi, Mattia Zaghi, Raquel Moll-Diaz, Luca Massimino, Laura Argelich, Edoardo Bellini, Simone Bido, Sharon Muggeo, Gabriele Ordazzo, Giuseppina Mastrototaro, Matteo Moneta, Alessandro Sessa, Vania Broccoli
Summary: By rational engineering of the transcription factor SOX2, a synthetic repressor named SOX2 epigenetic silencer (SES) was generated, which can effectively kill glioma cells and prolong patient survival. In experiments, SES expression significantly inhibits tumor growth without harming neurons and glia.
Article
Biochemical Research Methods
Marta Massano, Enrico Gerace, Martina Borsari, Matteo Marti, Micaela Tirri, Christina Ververi, Eugenio Alladio, Marco Vincenti, Alberto Salomone
Summary: This study investigated the distribution of the dissociative drug MXPr and its metabolites in body fluids and fur of mice. The main metabolite identified in urine was Desmethyl-MXPr-glucoronide, and norMXPr was also present in urine, plasma, and fur. These findings can contribute to the toxicological screening and extending the detection window of MXPr.
DRUG TESTING AND ANALYSIS
(2023)
Article
Clinical Neurology
Elena Espa, Lu Song, Katrine Skovgard, Silvia Fanni, M. Angela Cenci
Summary: This study investigated the impact of adjunct treatment with the D2/3 agonist ropinirole on levodopa-induced dyskinesia (LID)-related neuroplasticity and drug responses. The results showed distinct differences in neuroplasticity and pharmacological responses between rats receiving levodopa monotherapy and those receiving levodopa-ropinirole combination therapy. These findings suggest that the adjuvant dopamine agonist treatment should be considered when studying and treating LID in both clinical and experimental settings.
MOVEMENT DISORDERS
(2023)
Article
Neurosciences
Giorgia Corli, Micaela Tirri, Raffaella Arfe, Beatrice Marchetti, Tatiana Bernardi, Martina Borsari, Sara Odoardi, Serena Mestria, Sabina Strano-Rossi, Margherita Neri, Rosa Maria Gaudio, Sabrine Bilel, Matteo Marti
Summary: Synthetic cathinones, including MTTA, are becoming increasingly popular in the illicit drug market, particularly among young adults, due to their ability to replicate the effects of traditional psychostimulant drugs. However, there is limited data available on the in vivo pharmaco-toxicology of these substances. This study examined the effects of repeated administration of MTTA in mice and found that it caused sensory and physiological changes, as well as histological alterations in the heart, kidney, and liver, suggesting potential toxicity.
Article
Hematology
Marta Biondi, Sarah Tettamanti, Stefania Galimberti, Beatrice Cerina, Chiara Tomasoni, Rocco Piazza, Samantha Donsante, Simone Bido, Vincenzo Maria Perriello, Vania Broccoli, Andrea Doni, Francesco Dazzi, Alberto Mantovani, Gianpietro Dotti, Andrea Biondi, Alice Pievani, Marta Serafini
Summary: Acute myeloid leukemia (AML) is a hematological malignancy characterized by abnormal clonal proliferation and differentiation. The efficacy of chimeric antigen receptor (CAR)-T-cell therapy in AML has been hindered by factors such as poor accumulation in the leukemia bone marrow niche. Overexpression of CXCR4 in CAR-T cells may improve T-cell homing to the bone marrow and enhance their contact with AML cells, potentially increasing their therapeutic potential. In conclusion, arming CAR-T cells with CXCR4 represents a promising strategy for AML treatment.
Article
Substance Abuse
Giorgia Corli, Micaela Tirri, Sabrine Bilel, Arianna Giorgetti, Tatiana Bernardi, Federica Boccuto, Martina Borsari, Raffaele Giorgetti, Matteo Marti
Summary: This study investigates the acute effects of co-administration of JWH-018 and ethanol on sensorimotor and motor responses, grip strength, and memory functions in mice. The results show that the combination of JWH-018 and ethanol leads to worsened cognitive and sensorimotor disruptions.
DRUG AND ALCOHOL DEPENDENCE
(2023)
Article
Biochemistry & Molecular Biology
Monia Lenzi, Sofia Gasperini, Giorgia Corli, Matteo Marti, Patrizia Hrelia
Summary: MTTA, a novel psychoactive substance with a similar structure to cathinone, has not been extensively studied for its pharmaco-toxicological profile and genotoxic potential. This study aimed to evaluate its genotoxicity on TK6 cells by assessing its ability to induce chromosomal aberrations using the In Vitro Mammalian Cell Micronucleus (MN) test. The results showed no statistically significant increase in the frequency of micronuclei, except at a concentration of 50 μM after long-term treatment (26 hours).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Beatrice Marchetti, Sabrine Bilel, Micaela Tirri, Giorgia Corli, Elisa Roda, Carlo Alessandro Locatelli, Elena Cavarretta, Fabio De-Giorgio, Matteo Marti
Summary: JWH-018 is a known compound used for its psychoactive effects, but it also has toxic effects on the cardiovascular and respiratory systems. This study investigated the effects of different antidotes on the cardiovascular and respiratory responses to JWH-018 in male mice. The results showed that while all tested antidotes reduced tachycardia and tachyarrhythmia and improved breathing functions, only atropine completely reversed the heart rate and pulse distension. These findings provide valuable information for the treatment of intoxicated patients in emergency clinical settings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Chang Li, Osama F. Elabi, Tim Fieblinger, M. Angela Cenci
Summary: The dendritic arbour of striatal projection neurons undergoes atrophic changes in Parkinson's disease. In a mouse model of dopamine denervation, spiny projection neurons in the direct pathway show coordinated changes in dendritic morphology, intrinsic excitability, and Kir conductances at 28 days post-lesion, which may interfere with their normal movement-related output.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2023)
Review
Neurosciences
Sabrine Bilel, Arianna Giorgetti, Micaela Tirri, Raffaella Arfe, Virginia Cristofori, Beatrice Marchetti, Giorgia Corli, Lorenzo Caruso, Giorgio Zauli, Raffaele Giorgetti, Matteo Marti
Summary: Driving is a complex task that requires coordination of cognitive functions and psychomotor skills. The effects of novel psychoactive substances (NPS) and novel synthetic opioids (NSO) on driving ability are still unclear. This study presents a literature review on the psychomotor impairing effects of Fentanyl (FENT) and three analogues in humans. Experimental studies on both humans and mice showed that FENT and its analogues dose-dependently decreased visual and sensory responses, suggesting that these synthetic opioids may impair psychomotor performance, particularly in driving.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Neurosciences
Nihal A. Salem, Lawrence Manzano, Michael W. Keist, Olga Ponomareva, Amanda J. Roberts, Marisa Roberto, R. Dayne Mayfield
Summary: This study identified cell-type specific gene expression changes associated with alcohol dependence in the medial prefrontal cortex of mice. The results revealed dysregulated gene co-expression networks and differentially expressed genes in multiple cell types, highlighting the involvement of inhibitory neurons and astrocytes in alcohol dependence. Novel targets for studying molecular mechanisms contributing to alcohol dependence were also identified.
NEUROBIOLOGY OF DISEASE
(2024)
Article
Neurosciences
Laura E. Hawley, Megan Stringer, Abigail J. Deal, Andrew Folz, Charles R. Goodlett, Randall J. Roper
Summary: This study found that the overexpression of DYRK1A protein in Down syndrome mice varies with age, sex, and brain region, and reducing the copy number of Dyrk1a can decrease the expression of DYRK1A. These sex-specific patterns of DYRK1A overexpression may provide mechanistic targets for therapeutic intervention in Down syndrome.
NEUROBIOLOGY OF DISEASE
(2024)