Article
Behavioral Sciences
Yang Tan, Chi Cheng, Cong Zheng, Weiqi Zeng, Xiaoman Yang, Yu Xu, Zhaoyuan Zhang, Zhuoran Ma, Yan Xu, Xuebing Cao
Summary: The activation of striatal mGlu(2/3) receptors can attenuate the development of dyskinesia in parkinsonism rats and provide some functional improvements in LID rats by inhibiting LID-related molecular changes.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
Article
Neurosciences
Osama F. Elabi, Rachel Pass, Irene Sormonta, Sara Nolbrant, Nicola Drummond, Agnete Kirkeby, Tilo Kunath, Malin Parmar, Emma L. Lane
Summary: The study found that L-DOPA did not have a negative impact on the survival and functional recovery of hESC-derived dopaminergic neuron transplants, potentially enhancing graft maturation and promoting an A9 phenotype. Early improvement of L-DOPA-induced dyskinesia suggests that grafts may handle exogenously supplied dopamine earlier than improvements in amphetamine-induced behaviors indicate. This information is vital for the management of patients and achieving optimal outcomes following transplantation of hESC-derived grafts for PD.
JOURNAL OF PARKINSONS DISEASE
(2022)
Article
Geriatrics & Gerontology
Aijuan Yan, Lu Song, Yu Zhang, Xijin Wang, Zhenguo Liu
Summary: Systemic inflammation exacerbates levodopa-induced dyskinesia (LID) by increasing neuroinflammation and NR2B subunit activity. The use of clodronate-encapsulated liposomes can suppress the inflammatory response and improve behavioral dysfunction, reducing susceptibility to LID.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Immunology
Chang-Qing Zheng, Hong-Xia Fan, Xiao-Xian Li, Jing-Jie Li, Shuo Sheng, Feng Zhang
Summary: Resveratrol (RES) has shown potential in alleviating dyskinesia associated with Parkinson's disease treatment, reducing the abnormal movements induced by L-DOPA while protecting DA neurons from long-term damage, and inhibiting neuroinflammatory reactions mediated by glial cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Neurosciences
Annalisa Pinna, Giulia Costa, Marcello Serra, Liliana Contu, Micaela Morelli
Summary: The study found that the combination of L-dopa, eltoprazine, and preladenant could potentially delay the onset of dyskinesia, maintain the efficacy of L-dopa, and reduce neuroinflammation markers in the nigrostriatal system of 6-OHDA-lesioned rats.
Article
Clinical Neurology
P. A. Caro Aponte, C. A. Otalora, J. C. Guzman, L. F. Turner, J. P. Alcazar, E. L. Mayorga
Summary: The study aimed to develop and standardize an experimental model of L-DOPA-induced dyskinesia in rats, and evaluate the correlation between D2R expression and abnormal involuntary movements (AIM). The results suggest an association between D2R expression and locomotor AIMs.
Review
Neurosciences
Kai Yang, Xinyue Zhao, Changcai Wang, Cheng Zeng, Yan Luo, Taolei Sun
Summary: LID is a common issue in the treatment of Parkinson's disease, involving damage to multiple brain regions, with various theoretical models proposed to explain its mechanisms, necessitating a deeper understanding.
FRONTIERS IN NEUROSCIENCE
(2021)
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
Gunasingh J. Masilamoni, Christopher G. Sinon, Brik A. Kochoian, Arun Singh, Andrew J. McRiner, Liza Leventhal, Stella M. Papa
Summary: This study assessed the effects of a selective PDE9 inhibitor (PDE9i) in a primate model of Parkinson's disease (PD). The results showed that PDE9i enhanced the antiparkinsonian effects of L-DOPA and prolonged its duration of action. This suggests that striatal PDE9 inhibition may be a strategy to improve motor responses to L-DOPA in PD.
Article
Biochemistry & Molecular Biology
Andrea Lopez-Lopez, Rita Valenzuela, Ana Isabel Rodriguez-Perez, Maria J. Guerra, Jose Luis Labandeira-Garcia, Ana Munoz
Summary: Statins have been proposed for the treatment of L-DOPA-induced dyskinesia (LID), and their anti-dyskinetic effects may be related to the inhibition of the Ras-ERK pathway. The mechanisms responsible for the anti-LID effect are unclear, but they could involve changes in cholesterol homeostasis and oxidative stress- and inflammation-related mechanisms. Angiotensin II, cholesterol, and Rho-kinase pathways have been found to interact in LID, and their inhibition by specific drugs may attenuate the dyskinetic symptoms.
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
Biochemistry & Molecular Biology
Goichi Beck, Jie Zhang, Kayoko Fong, Hideki Mochizuki, M. Maral Mouradian, Stella M. Papa
Summary: The study reveals that suppressing striatal increment FosB gene can effectively control L-Dopa-induced dyskinesia in rodents without affecting the antiparkinsonian action of L-Dopa, suggesting a potential therapeutic strategy to reduce increment FosB levels in patients with PD.
Article
Neurosciences
Indriani Dwi Wahyu, Satomi Chiken, Taku Hasegawa, Hiromi Sano, Atsushi Nambu
Summary: Studies using a PD mouse model showed that GPe and SNr neurons exhibited different spontaneous activity and cortically evoked responses in the PD and dyskinesia states, suggesting that the occurrence of LID is associated with the neural activity patterns of these two nuclei.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Clinical Neurology
Rodrigo Manuel Paz, Cecilia Tubert, Agostina Monica Stahl, Yimy Amarillo, Lorena Rela, Mario Gustavo Murer
Summary: Enhanced striatal cholinergic interneuron activity contributes to the striatal hypercholinergic state in Parkinson's disease and levodopa-induced dyskinesia. Dysregulation of D5-cAMP signaling and membrane ion channels in cholinergic interneurons causes aberrant burst-pause firing, which can be dampened by pharmacological intervention, providing a potential therapeutic target for alleviating parkinsonism and dyskinesia.
MOVEMENT DISORDERS
(2021)
Article
Geriatrics & Gerontology
Hiromi Sano, Atsushi Nambu
Summary: ZNS is an anticonvulsant drug that has beneficial effects on Parkinson's disease and its side effect, L-DOPA-induced dyskinesia, but can also have adverse effects.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Clinical Neurology
Marc Morissette, Therese Di Paolo
JOURNAL OF NEURAL TRANSMISSION
(2018)
Article
Behavioral Sciences
Melanie Bourque, Laurent Gregoire, Therese Di Paolo
BEHAVIOURAL BRAIN RESEARCH
(2018)
Review
Neurosciences
Melanie Bourque, Marc Morissette, Therese Di Paolo
Article
Clinical Neurology
Delphine Charvin, Therese Di Paolo, Erwan Bezard, Laurent Gregoire, Akihiro Takano, Guillaume Duvey, Elsa Pioli, Christer Halldin, Rossella Medori, Francois Conquet
MOVEMENT DISORDERS
(2018)
Editorial Material
Neurosciences
F. Gasparini, T. Di Paolo
Article
Endocrinology & Metabolism
Hend Jarras, Melanie Bourque, Andree-Anne Poirier, Marc Morissette, Katherine Coulombe, Therese Di Paolo, Denis Soulet
JOURNAL OF NEUROENDOCRINOLOGY
(2020)
Article
Neurosciences
Jordan Nadeau, Tara Smith, Jerome Lamontagne-Proulx, Melanie Bourque, Sara Al Sweidi, Dushmanthi Jayasinghe, Shawn Ritchie, Therese Di Paolo, Denis Soulet
Article
Immunology
Cynthia Lecours, Marie-Kim St-Pierre, Katherine Picard, Maude Bordeleau, Melanie Bourque, Ifeoluwa Oluleke Awogbindin, Amin Benadjal, Fernando Gonzalez Ibanez, Dave Gagnon, Leo Cantin, Martin Parent, Therese Di Paolo, Marie-Eve Tremblay
BRAIN BEHAVIOR AND IMMUNITY
(2020)
Review
Neurosciences
Ifeoluwa Oluleke Awogbindin, Ismail Ogunbayode Ishola, Marie-Kim St-Pierre, Micael Carrier, Julie C. Savage, Therese Di Paolo, Marie-Eve Tremblay
NEUROSCIENCE LETTERS
(2020)
Article
Neurosciences
Amandine Isenbrandt, Marc Morissette, Melanie Bourque, Jerome Lamontagne-Proulx, Katherine Coulombe, Denis Soulet, Therese Di Paolo
Summary: The study examined the effects of sex hormones on a mouse model of Parkinson's disease and the neuroprotective role of the 5 alpha-reductase inhibitor dutasteride. Results showed sex differences in mice MPTP toxicity and response to dutasteride, with implications of neuroinflammation.
Review
Neurosciences
Ifeoluwa O. Awogbindin, Benneth Ben-Azu, Babatunde A. Olusola, Elizabeth T. Akinluyi, Philip A. Adeniyi, Therese Di Paolo, Marie-Eve Tremblay
Summary: Since December 2019, humanity has been facing the devastating SARS-CoV-2 outbreak, resulting in over 3.1 million deaths globally. SARS-CoV-2 infection may lead to neurological symptoms and potentially cause chronic or permanent changes to neural tissues.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cell Biology
Marc Morissette, Melanie Bourque, Marie-Eve Tremblay, Therese Di Paolo
Summary: Inflammatory markers were found in the brains of Parkinson's disease patients. The study showed that MPEP reduced the development of L-Dopa-induced dyskinesias (LID) in MPTP-lesioned monkeys and decreased inflammatory markers in the brain. The results demonstrated increased inflammatory markers in the basal ganglia associated with LID and revealed the potential of MPEP in reducing LID and inflammatory response.
Article
Biochemical Research Methods
Valerie Brousseau, Patrick Caron, Jocelyn Trottier, Therese Di Paolo, Piotr Milkiewicz, Olivier Barbier
Summary: This study developed a method for quantification of 24S-hydroxycholesterol and its derivatives in human plasma and validated its clinical applications. The results indicate the accumulation of cerebrosterol and its conjugates in the plasma of cholestatic patients.
JOURNAL OF MASS SPECTROMETRY
(2022)
Article
Pharmacology & Pharmacy
Andree-Anne Poirier, Melissa Cote, Hend Jarras, Nadhir Litim, Jerome Lamontagne-Proulx, Sara Al-Sweidi, Marc Morissette, Asmaa Lachhab, Martin Pelletier, Therese Di Paolo, Denis Soulet
Summary: This study demonstrates that dutasteride can prevent enteric neuronal damage in the MPTP mouse model of Parkinson's disease by anti-inflammatory and mitochondrial effects, suggesting that drug repurposing of dutasteride might be a promising avenue to treat enteric neuroinflammation in early PD.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Melanie Bourque, Laurent Gregoire, Waseema Patel, David Dickens, Ralph Snodgrass, Therese Di Paolo
Summary: N-methyl-D-aspartate (NMDA) receptors have been implicated in L-Dopa-induced dyskinesias (LID) in Parkinson's disease patients. L-4-chlorokynurenine (AV-101) is a pro-drug of 7-chlorokynurenic acid, a specific antagonist of the glycine co-agonist site of NMDA receptors. This study investigated the effects of AV-101 on LID in MPTP-lesioned monkeys and found that it reduced LID and maintained the antiparkinsonian activity of L-Dopa. AV-101 showed comparable antidyskinetic activity to amantadine but without adverse effects.
Article
Neurosciences
Wenzhu Wang, Zihan Li, Yitong Yan, Shuo Wu, Xinyu Yao, Chen Gao, Lanxiang Liu, Yan Yu
Summary: This study investigated the reparative mechanisms of low-intensity pulsed ultrasound (LIPUS) in traumatic brain injury (TBI) and found that LIPUS promotes hippocampal neurogenesis, enhances neural electrical activity and neural plasticity, ultimately restoring neuronal function and cognitive capabilities in TBI mice.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Wenmin Yi, Fei Chen, Minghao Yuan, Chuanling Wang, Shengyuan Wang, Jie Wen, Qian Zou, Yinshuang Pu, Zhiyou Cai
Summary: The study suggests that a high-fat diet may lead to tau hyperphosphorylation and synaptic dysfunction by inhibiting the SIRT1/AMPK pathway and disrupting autophagy flux, ultimately resulting in cognitive decline.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Kim M. Hemsley, Helen Beard, Glyn Chidlow, Teresa Mammone, Leanne K. Winner, Daniel Neumann, Barbara King, Marten F. Snel, Paul J. Trim, Robert J. Casson
Summary: Optical coherence tomography (OCT) is a non-invasive method that can be used to rapidly and quantitatively examine the integrity of the neuroretina. It has been shown that OCT can be used to observe retinal thinning in patients with childhood dementia, and to assess the improvement of retinal structure after treatment. Furthermore, OCT can provide insights into other childhood dementias based on the correlation between retinal and brain degeneration in Sanfilippo syndrome.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Qianling Jiang, Xin Ma, Gaochen Zhu, Wen Si, Lingyu He, Guan Yang
Summary: This study investigated the effects of EAE induction on thymopoiesis and T cell development, revealing changes such as increased apoptosis, decreased proliferation, and a blockade in the transition from double-negative thymocytes to double-positive cells. It was also found that positive selection was disrupted in the thymus of EAE mice, along with an increased production of regulatory T cells.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Alice McDouall, Guido Wassink, Sumudu Ranasinghe, Kelly Q. Zhou, Rashika N. Karunasinghe, Justin M. Dean, Joanne O. Davidson
Summary: This study found that blocking connexin 43 hemichannels can attenuate brain injury and promote neurodevelopment in infants with mild hypoxic-ischemic encephalopathy, without causing hypothermia.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Hannah Sweetman, Mahmudur Rahman, Aditya Vedantam, Kajana Satkunendrarajah
Summary: Degenerative cervical myelopathy (DCM) is a neurological condition characterized by chronic compression of the cervical spinal cord, leading to impaired limb function. While respiratory dysfunction is not a common symptom of DCM, it can affect the ventilatory response to respiratory challenges. Surgical decompression improves sensorimotor function in DCM, but its impact on respiratory function is unclear. This study evaluates respiratory function and adaptive ventilation in a DCM model, showing that DCM impairs acute adaptive ventilatory ability and surgical decompression does not fully restore it.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Chengmei Sun, Muhammad Saif Ur Rahman, Budbazar Enkhjargal, Jianhua Peng, Keren Zhou, Zhiyi Xie, Lingyun Wu, Tongyu Zhang, Qiquan Zhu, Jiping Tang, Yujia Zeng, John H. Zhang, Shanshan Xu
Summary: This study found that Osteopontin (OPN) can attenuate inflammatory responses after subarachnoid hemorrhage (SAH) by promoting an anti-inflammatory microglial state. This effect may be mediated through the integrin-FAK-STAT3 and NF-kappa B signaling pathways.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Neurosciences
Yang Yang, Xuezhu Chen, Chuanyan Yang, Mei Liu, Qianying Huang, Likun Yang, Yuhai Wang, Hua Feng, Zhongyang Gao, Tunan Chen
Summary: The study explores the effects of specific chemogenetic stimulation of intact corticospinal tract on functional recovery after stroke in mice. The findings demonstrate that combining chemogenetic activation with rehabilitation training leads to significant motor functional recovery by promoting axon sprouting and rewiring new functional circuits.
EXPERIMENTAL NEUROLOGY
(2024)