Article
Multidisciplinary Sciences
Julia Hunter, Alexandra Bova, Andrew Stevens, Daniel K. Leventhal
Summary: With continued levodopa treatment, most patients with Parkinson's disease develop levodopa-induced dyskinesias (LIDs), which are abnormal involuntary movements characterized primarily by chorea. LIDs depend on nigrostriatal degeneration and repeated levodopa doses, but pulsatile dopamine release may also induce AIMs independently of nigrostriatal degeneration. Optogenetic stimulation of dopamine neurons in healthy rats during skilled reaching experiments revealed that repeated stimulation induced progressive AIMs, and the severity of AIMs was influenced by behavioral context. Furthermore, AIMs recurred immediately with subsequent dopamine neuron activation, suggesting that nigrostriatal denervation is not necessary for fluctuating striatal dopamine to induce AIMs.
Article
Neurosciences
Margaret E. Caulfield, Molly J. Vander Werp, Jennifer A. Stancati, Timothy J. Collier, Caryl E. Sortwell, Ivette M. Sandoval, Fredric P. Manfredsson, Kathy Steece-Collier
Summary: Over the past 25 years, the prevalence of Parkinson's disease (PD) has increased significantly. In our study, we found that silencing CaV1.3 channels can prevent levodopa-induced dyskinesia (LID) in PD patients. However, the response to gene therapy varies among individuals, especially with increasing age.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Melissa M. Conti Mazza, Ashley Centner, David F. Werner, Christopher Bishop
Summary: L-DOPA is the standard treatment for Parkinson's disease, but chronic treatment leads to L-DOPA-induced dyskinesia. This study found that dopamine depletion and L-DOPA treatment alter the expression and function of dopamine and serotonin transporters, suggesting their potential as biomarkers and therapeutic targets for dyskinesia in Parkinson's disease patients.
Article
Clinical Neurology
Chiara Melis, Genevieve Beauvais, Brian S. Muntean, Maria-Daniela Cirnaru, Garrett Otrimski, Jordi Creus-Muncunill, Kirill A. Martemyanov, Pedro Gonzalez-Alegre, Michelle E. Ehrlich
Summary: This study investigated whether mouse models of monogenic dystonia exhibit molecular features of levodopa-induced dyskinesia. Results suggest that different genetic types of dystonia show varying responses to dopamine, indicating abnormal signal transduction in the postsynaptic nigrostriatal pathway may be a potential point of convergence for dystonia and other hyperkinetic movement disorders, offering common therapeutic targets.
MOVEMENT DISORDERS
(2021)
Article
Virology
Arkom Chaiwongkot, Supranee Buranapraditkun, Shina Oranratanaphan, Thanaporn Chuen-Im, Nakarin Kitkumthorn
Summary: Cervical cancer screening typically involves a Pap smear combined with high-risk human papillomavirus (hr-HPV) detection. Bioinformatics analysis identified a methylation marker cg01009664, which can enhance the accuracy of detecting CIN2+. The real-time PCR assay demonstrates high sensitivity and specificity in identifying CIN2+ and can effectively aid in the diagnosis of cervical lesions.
Article
Neurosciences
Yong Wang, Lu Yao, Shasha Gao, Gejuan Zhang, Qiongchi Zhang, Wanyuan Liu, Yingqiong Zhou, Yina Sun, Jie Feng, Jian Liu
Summary: The study found that the striatal dopamine D-5 receptor plays an important role in the pathophysiology of levodopa-induced dyskinesia in patients with Parkinson's disease, by regulating the activity of sensorimotor striatum neurons to affect the development of dyskinetic symptoms.
Review
Endocrinology & Metabolism
Ivan Lazcano, Adair Rodriguez Rodriguez, Rosa Maria Uribe, Aurea Orozco, Patricia Joseph-Bravo, Jean-Louis Charli
Summary: Thyroid hormones are ancient signaling molecules that regulate metabolism and growth in vertebrates through the hypothalamus-pituitary-thyroid axis. The hypothalamic factors that induce TSH secretion vary among vertebrates, but all play a role in activating TH synthesis in the thyroid gland.
GENERAL AND COMPARATIVE ENDOCRINOLOGY
(2021)
Article
Neurosciences
Rose B. Creed, Rosalinda C. Roberts, Charlene B. Farmer, Lori L. McMahon, Matthew S. Goldberg
Summary: Loss-of-function PTEN Induced Kinase1 (PINK1) mutations lead to early-onset familial Parkinson's disease (PD) with similar characteristics to idiopathic PD. Knockout of Pink1 in rats leads to increased excitability of presynaptic neurons, altered glutamate release probability, and abnormal synaptic vesicle pool recovery, potentially contributing to striatal circuit dysfunction in PD.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
Cynthia Kwan, Catherine Levesque, Dominique Bedard, Imane Frouni, Jemal M. Yesuf, Adjia Hamadjida, Daniel Levesque, Paul Bs Clarke, Philippe Huot
Summary: Serotonin type 3 antagonists can alleviate dyskinesia induced by L-DOPA and enhance its anti-parkinsonian action. The results suggest that alterations in 5-HT3 mediated neurotransmission may contribute to the pathophysiology of L-DOPA induced dyskinesia.
NEUROSCIENCE RESEARCH
(2022)
Article
Physiology
Wen-Ying Liu, Raina Ladha, Hattie Liu, Richard L. Horner
Summary: The study found that Taltirelin is a stable upper airway-preferring respiratory stimulant that increases muscle activity and arousal, while suppressing non-REM sleep. These traits have potential favorable relevance to some respiratory disorders.
JOURNAL OF APPLIED PHYSIOLOGY
(2022)
Article
Neurosciences
Carla M. V. Dias, Denisson A. B. Leal, Ivani Brys
Summary: This study aimed to identify clinical and behavioral features that could predict the future development of Levodopa-induced dyskinesia (LID) in Parkinson's Disease (PD) patients. The results showed that higher levels of trait anxiety and increased motor impairment were present before LID onset in PD patients. Additionally, younger age at PD diagnosis, earlier need for dopaminergic therapy, and higher initial levodopa dose were associated with the development of LID in the future.
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2022)
Article
Agriculture, Dairy & Animal Science
E. L. Oberhaus, D. L. Thompson, L. E. Kerrigan, A. M. Chapman
Summary: The study aimed to assess the effects of DET and DET/BUT on endocrine responses to TRH, finding that the drugs altered the responses of prolactin, TSH, MSH, and ACTH to TRH.
DOMESTIC ANIMAL ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Feras Altwal, Fernando E. Padovan-Neto, Alexandra Ritger, Heinz Steiner, Anthony R. West
Summary: Research has shown that vilazodone may reduce dyskinesia in patients with Parkinson's disease without interfering with the prokinetic effects of L-DOPA, possibly through its action on 5-HT receptors.
Article
Cell Biology
Zdenka Drastichova, Radka Trubacova, Jiri Novotny
Summary: In recent years, it has been discovered that thyrotropin-releasing hormone (TRH) and its analogs have the potential to be therapeutic agents for treating neurological disorders. However, the molecular mechanisms behind their actions are still not well understood. This study investigated the effects of TRH and one of its analogs, taltirelin, on phosphosignaling dynamics in pituitary cells and explored the role of beta-arrestin in mediating these effects. The findings suggest that compounds that modulate kinase and phosphatase activity can enhance the therapeutic potential of TRH or its analogs.
Article
Endocrinology & Metabolism
Jesse M. Lacasse, Vanessa Boulos, Caleigh Fisher, Sarran Hamilton, Megan Heron, Conall E. Mac Cionnaith, Vanessa Peronace, Noemie Tito, Wayne G. Brake
Summary: The study found that synthetic hormones contained in oral contraceptives can influence the cognitive strategies used by female animals during maze navigation.
PSYCHONEUROENDOCRINOLOGY
(2023)
Article
Neurosciences
Jill R. Crittenden, Theresa A. Gipson, Anne C. Smith, Hilary A. Bowden, Ferah Yildirim, Kyle B. Fischer, Michael Yim, David E. Housman, Ann M. Graybiel
Summary: The study identified changes in gene expression in the striatum of mice treated with amphetamine, with abnormal plasticity occurring alongside drug-induced stereotypic behavior. Genes encoding members of the ERK cascades were found to be involved in psychomotor stimulant responses. Dysregulation of 20 genes, particularly those regulated by neuregulin 1, was observed in the sensitized group with prolonged stereotypy. These findings suggest a potential link between drug-induced sensitization of the Nrg1 signaling pathway and disorders such as schizophrenia and autism characterized by behavioral stereotypy.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemical Research Methods
Mads L. Pedersen, Maria Ironside, Ken-ichi Amemori, Callie L. McGrath, Min S. Kang, Ann M. Graybiel, Diego A. Pizzagalli, Michael J. Frank
Summary: This study utilizes a drift diffusion model to investigate how reward and aversiveness influence decision making, finding that individuals with major depressive disorder have reduced reward sensitivity, tend to avoid offers, and exhibit significant brain activity effects on behavior.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Neurosciences
Camarin E. Rolle, Mads L. Pedersen, Noriah Johnson, Ken-Ichi Amemori, Maria Ironside, Ann M. Graybiel, Diego A. Pizzagalli, Amit Etkin
Summary: This article investigates the role of the dorsolateral prefrontal cortex (dlPFC) in approach-avoidance conflict (AAC) behavior using transcranial magnetic stimulation (TMS) and drift-diffusion modeling. It demonstrates that disrupting the dlPFC reduces reward sensitivity during conflict decision-making and identifies its network of cortical regions associated with avoidance behavior. These findings advance our understanding of the neural mechanisms underlying AAC behavior and suggest the dlPFC as a potential target for psychiatric therapeutics.
Article
Biochemistry & Molecular Biology
Morgane Thomsen, Jill R. Crittenden, Craig W. Lindsley, Ann M. Graybiel
Summary: Stimulation of muscarinic acetylcholine receptors M-1 and M-4 holds promise as a potential pharmacotherapy for cocaine use disorder. Previous studies have shown that M-4 stimulation can reduce the effects of cocaine, and combined M-1/M-4 stimulation or M-1 stimulation alone can lead to long-lasting reductions in cocaine taking and seeking. This research aims to determine whether M-4 approaches remain effective with repeated or chronic dosing, and the results indicate that M-4 positive allosteric modulators (PAMs) can progressively suppress cocaine choice and intake without rebound or lasting effects after treatment ends. Additionally, the effects of M-1 versus M-4 stimulation on cocaine self-administration were compared, revealing that M-4-mediated suppression of cocaine self-administration is not dependent on the CalDAG-GEFI signaling factor required for M-1-mediated suppression. These findings support the potential usefulness of M-4 PAMs as pharmacotherapy for managing cocaine use disorder, either alone or in combination with M-1-selective ligands, and suggest that M-1 and M-4 stimulation modulate cocaine-taking behavior through distinct mechanisms.
Article
Multidisciplinary Sciences
Bernard Bloem, Rafiq Huda, Ken-ichi Amemori, Alex S. Abate, Gayathri Krishna, Anna L. Wilson, Cody W. Carter, Mriganka Sur, Ann M. Graybiel
Summary: The striatal neurons can encode associations between actions and multiple rewarding and aversive outcomes. Striosomal neurons are particularly important in action-outcome learning.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Rekha Dhanwani, Joao Rodrigues Lima-Junior, Ashu Sethi, John Pham, Gregory Williams, April Frazier, Yaqian Xu, Amy W. Amara, David G. Standaert, Jennifer G. Goldman, Irene Litvan, Roy N. Alcalay, Bjoern Peters, David Sulzer, Cecilia S. Lindestam Arlehamn, Alessandro Sette
Summary: This study performed RNA sequencing on T cells derived from Parkinson's disease (PD) patients and healthy controls, revealing a broad differential gene expression profile and specific PD-associated gene signature in memory T cell subsets of PD patients. These findings provide insights into the role of T cells in PD pathogenesis and suggest potential intervention targets.
NPJ PARKINSONS DISEASE
(2022)
Article
Neurosciences
Jill R. Crittenden, Tomoko Yoshida, Samitha Venu, Ara Mahar, Ann M. Graybiel
Summary: CB1R plays a crucial role in the postnatal wiring of the brain's cannabinoid circuit, affecting the connectivity between striatal and dopaminergic neurons. Lack of CB1R expression can lead to disorganized brain connections and altered dopaminergic neuron activity.
Biographical-Item
Clinical Neurology
Howard I. Hurtig, David G. Standaert
MOVEMENT DISORDERS
(2022)
Article
Multidisciplinary Sciences
Zachary D. Wallen, Ayse Demirkan, Guy Twa, Gwendolyn Cohen, Marissa N. Dean, David G. Standaert, Timothy R. Sampson, Haydeh Payami
Summary: The authors conducted a large-scale metagenomics analysis comparing gut microbiomes of Parkinson's disease patients and healthy individuals, revealing dysbiosis in PD and confirming the importance of the gut microbiome in PD pathogenesis.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Ayano Matsushima, Sergio Sebastian Pineda, Jill R. Crittenden, Hyeseung Lee, Kyriakitsa Galani, Julio Mantero, Geoffrey Tombaugh, Manolis Kellis, Myriam Heiman, Ann M. Graybiel
Summary: In human and mouse models of Huntington's disease, the two defining axes of striatal projection neurons are mixed and differentially affected. The indirect-pathway striatal projection neurons are the most depleted in human patients, while the transcriptomic distinctiveness of striosome-matrix neurons is diminished more in mouse models. The loss of striosome-matrix distinction is more prominent within the indirect-pathway neurons, suggesting the need for distinct therapeutic strategies based on the differential compromise of these two axes.
NATURE COMMUNICATIONS
(2023)
Article
Clinical Neurology
Hubert H. Fernandez, Per Odin, David G. Standaert, Tove Henriksen, Joohi Jimenez-shahed, Sharon Metz, Ali Alobaidi, Connie H. Yan, Pavnit Kukreja, Juan Carlos Parra, Jorge Zamudio, Koray Onuk, Jack Wright, Angelo Antonini
Summary: This study categorized Parkinson's disease patients using MANAGE-PD and examined their quality of life, healthcare resource utilization, and discussions about device-aided therapies. The findings showed that patients with poorly controlled symptoms and eligible for device-aided therapies had higher burden on healthcare resources but a significant portion did not discuss device-aided therapies with providers.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Multidisciplinary Sciences
A. M. Schonhoff, D. A. Figge, G. P. Williams, A. Jurkuvenaite, N. J. Gallups, G. M. Childers, J. M. Webster, D. G. Standaert, J. E. Goldman, A. S. Harms
Summary: Neuroinflammatory mechanisms are involved in Parkinson disease. We identified border-associated macrophages (BAMs) as crucial for the α-synuclein-mediated neuroinflammatory response through class II antigen presentation and T cell infiltration. Our findings highlight the role of BAMs in mediating the pathogenesis of Parkinson disease.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Haydeh Payami, Gwendolyn Cohen, Charles F. Murchison, Timothy R. Sampson, David G. Standaert, Zachary D. Wallen
Summary: Parkinson's disease is a rapidly growing neurological disorder with no known prevention methods. While intrinsic risk factors like age, sex, and genetics cannot be avoided, environmental factors can. This study suggests that repeated blows to the head in sports/combat may be a potential new risk factor. Approximately 23% of Parkinson's disease cases in females and 30% in males could be attributed to pesticide/herbicide exposure, military-related chemical exposures, and repeated blows to the head, highlighting the potential for prevention.
NPJ PARKINSONS DISEASE
(2023)
