Review
Cell Biology
Bradley M. Roberts, Emanuel F. Lopes, Stephanie J. Cragg
Summary: Striatal dopamine release is inhibited by striatal gamma-aminobutyric acid (GABA) acting via GABA(A) and GABA(B) receptors, which is regulated by plasma membrane GABA uptake transporters on striatal astrocytes. The regulation of striatal GABA-DA interactions serves as a potential therapeutic target for psychomotor disorders associated with dysregulated DA signaling.
Review
Biochemistry & Molecular Biology
Joanna Sikora, Abdel-Mouttalib Ouagazzal
Summary: Alterations in zinc homeostasis have long been implicated in Parkinson's disease, with both deficiency and excess of intracellular zinc levels playing a role in the pathophysiology. Zn2+ acts as a synaptic transmitter in the brain, particularly in glutamatergic neurons projecting to the striatum. Overactivation of the cortico-striatal glutamatergic system is a key feature contributing to the development of PD symptoms and dopaminergic neurotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Chloe Geoffroy, Pierre Paoletti, Laetitia Mony
Summary: NMDA receptors play essential roles in synaptic transmission and plasticity, with both hyper- and hypo-activation being detrimental to neuronal function. Recent developments in NMDAR positive allosteric modulators (PAMs) have provided new insights into potential treatments for conditions like schizophrenia and Alzheimer's disease. Further research is needed to fully understand the physiological effects and therapeutic potential of these modulators in vivo.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Neurosciences
G. Martella, P. Bonsi, P. Imbriani, G. Sciamanna, H. Nguyen, L. Yu-Taeger, M. Schneider, S. M. Poli, R. Lutjens, A. Pisani
Summary: Impairment of long-term synaptic plasticity is a unique endophenotype of certain forms of dystonia. Broad-spectrum antimuscarinic drugs and negative allosteric modulators of metabotropic glutamate receptor subtypes may be potential therapeutic options for dystonia treatment. The findings suggest common signaling pathway dysfunction among distinct dystonia genes and indicate the potential of dipraglurant as a novel therapeutic agent for this debilitating disorder.
Article
Biochemistry & Molecular Biology
Ornela Kljakic, Helena Janickova, Miguel Skirzewski, Amy Reichelt, Sara Memar, Salah El Mestikawy, Yulong Li, Lisa M. Saksida, Timothy J. Bussey, Vania F. Prado, Marco A. M. Prado
Summary: In the striatum, cholinergic interneurons can release both acetylcholine and glutamate, and their individual and combined contributions to behavior regulation were assessed in mice using reward-based touchscreen tests. Changes in VAChT and VGLUT3 levels have different effects on reward responses, and the simultaneous loss of both vesicular transporters affects dopamine signaling and behavior in a more severe way than the loss of VAChT alone. This shows that the ability of CINs to secrete two different neurotransmitters allows for complex modulation of various behaviors.
Editorial Material
Biochemistry & Molecular Biology
Samuel Caton, Adam Dewan
Summary: New research shows that human olfactory receptors can have stronger responses to odors through the non-competitive binding of an allosteric modulator. This modulation mechanism adds complexity to how scents are encoded in the peripheral system.
Article
Medicine, Research & Experimental
Roger L. Albin, Prabesh Kanel, Teus van Laar, Sygrid van der Zee, Stiven Roytman, Robert A. Koeppe, Peter J. H. Scott, Nicolaas Bohnen
Summary: This study examined the association between regional brain [F-18]FEOBV PET binding and the use of dopamine D2-like receptor agonist drugs in subjects with Parkinson's disease (PD). The results showed that chronic use of D2-like dopamine agonists in PD subjects did not lead to significant alterations in regional brain [F-18]FEOBV binding.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Arthur Cardoso Souto, Matheus Heidemann Tempone, Lyslie Azeredo Coutinho Goncalves, Vladimir Pedro Peralva Borges-Martins, Maria Carolina Peixoto-Rodrigues, Ana Clara Oliveira Damascena, Gabriel Ferraz, Alex Christian Manhaes, Newton Goncalves Castro, Ricardo Augusto de Melo Reis, Ana Lucia Marques Ventura, Regina Celia Cussa Kubrusly
Summary: Nicotine influences the development of avian embryo retina by reducing GABA uptake and increasing release through NMDAR and PKC pathways, as well as promoting calcium influx.
NEUROCHEMICAL RESEARCH
(2023)
Article
Neurosciences
Kelsey Barcomb, Christopher P. Ford
Summary: This review summarizes the previous work on the changes in neurotransmitter co-release and circuit dysfunction associated with the degeneration of midbrain dopamine neurons in Parkinson's disease.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Pharmacology & Pharmacy
Gabriela Starowicz, Dominika Siodlak, Gabriel Nowak, Katarzyna Mlyniec
Summary: This study aimed to investigate the role of glutamatergic and GABAergic system activation in TC-G 1008 antidepressant-like effects and the disruptions caused by a low-zinc diet. The results showed that the antidepressant-like effect of TC-G 1008 was blocked by NMDA and picrotoxin, and joint administration with muscimol or SCH50911 showed a trend towards decreased immobility time. A zinc-deficient diet resulted in dysregulation of GluN1, PSD95, and KCC2 protein expression. These findings suggest the important role of glutamate/GABA signaling in the antidepressant-like effect of TC-G 1008 and imply that GPR39 may be a novel target for the development of antidepressants.
PHARMACOLOGICAL REPORTS
(2023)
Article
Neurosciences
Daniel J. Liput, Henry L. Puhl, Ao Dong, Kaikai He, Yulong Li, David M. Lovinger
Summary: This study investigates the mechanisms of eCB mobilization in the DLS, and finds that brief bouts of synaptic stimulation induce long lasting eCB transients, mainly generated by 2-AG mobilization. The efficient mobilization of 2-AG requires coactivation of multiple receptors and is inhibited by dopamine D2 receptors.
Article
Neurosciences
Luke Ziolkowski, Isaac Mordukhovich, Daniel M. Chen, Mariangela Chisari, Hong-Jin Shu, Peter M. Lambert, Mingxing Qian, Charles F. Zorumski, Douglas F. Covey, Steven Mennerick
Summary: Neuroactive steroids are emerging as a new class of drugs for treating neuropsychiatric disorders, with effects on ligand-gated neurotransmitter receptors being a major mechanism of action. MQ-221, a sulfated, 3 beta-hydroxy neurosteroid analogue, inhibits NMDAR function while potentiating GABA(A)R function, showing potentially unique and clinically desirable effects. It may represent a new class of compound with unique psychoactive effects and beneficial prospects for treating neuropsychiatric disorders.
Review
Neurosciences
Karla Frydenvang, Darryl S. Pickering, Jette Sandholm Kastrup
Summary: This paper summarizes the interaction between positive allosteric modulators (PAMs) and the ligand-binding domain (LBD) of AMPA and kainate receptors based on structure determinations. PAMs are small molecules that enhance receptor currents by interfering with receptor desensitization and are considered to be of interest for pharmacological tool development. Potent PAMs have been identified for both AMPA and kainate receptors, with potential applications in brain disorder treatment and functional investigations.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Review
Cell Biology
Letizia Zanetti, Maria Regoni, Elena Ratti, Flavia Valtorta, Jenny Sassone
Summary: AMPARs play essential roles in both postsynaptic plasticity and presynaptic neurotransmitter release modulation. Recent studies suggest that presynaptic AMPARs may contribute to axonal pathology, pain transmission regulation, and auditory system physiology. These findings highlight the potential of presynaptic AMPARs as novel pharmacological targets for various pathological conditions.
Article
Immunology
Md Abdul Alim, Mirjana Grujic, Paul W. Ackerman, Per Kristiansson, Pernilla Eliasson, Magnus Peterson, Gunnar Pejler
Summary: Mast cells play a role in communication between peripheral nerves and immune cells, expressing glutamate receptors and being sensitive to glutamate signaling. Glutamate induces upregulation of various glutamate receptors and gene expression in mast cells, including pro-inflammatory components and transcription factors. The presence of a functional glutamate-glutamate receptor axis in mast cells is supported by in vitro and in vivo evidence, revealing a novel principle of communication between immune cells and nerve cells.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Clinical Neurology
Xiaoqun Zhang, Ze-Jun Feng, Karima Chergui
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2015)
Article
Neurosciences
Xiaoqun Zhang, Karima Chergui
Article
Biochemistry & Molecular Biology
N. Yao, O. Skiteva, X. Zhang, P. Svenningsson, K. Chergui
MOLECULAR PSYCHIATRY
(2018)
Article
Neurosciences
Olga Skiteva, Ning Yao, Mona Nouhi, Karima Chergui
NEUROSCIENCE LETTERS
(2018)
Article
Pharmacology & Pharmacy
Xiaoqun Zhang, Ioannis Mantas, Alexandra Alvarsson, Takashi Yoshitake, Mohammadreza Shariatgorji, Marcela Pereira, Anna Nilsson, Jan Kehr, Per E. Andren, Mark J. Millan, Karima Chergui, Per Svenningsson
FRONTIERS IN PHARMACOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Xiaoqun Zhang, Ze-Jun Feng, Karima Chergui
JOURNAL OF NEUROCHEMISTRY
(2014)
Article
Neurosciences
Giacomo Sitzia, Ioannis Mantas, Xiaoqun Zhang, Per Svenningsson, Karima Chergui
Article
Geriatrics & Gerontology
Xiaoqun Zhang, Ioannis Mantas, Elva Fridjonsdottir, Per E. Andren, Karima Chergui, Per Svenningsson
FRONTIERS IN AGING NEUROSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Olga Skiteva, Ning Yao, Giacomo Sitzia, Karima Chergui
Summary: This study reveals alterations in glutamatergic synaptic transmission in DA neurons of the SNc and VTA before the onset of motor impairments in the LRRK2-G2019S mouse model of PD.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Psychiatry
Olga Skiteva, Ning Yao, Karima Chergui
Summary: Ketamine may induce metaplasticity by altering the insertion of GluA2 subunit of AMPA receptors in VTA DA neurons and NAc SPNs. Ketamine reduces the insertion of CP-AMPARs in VTA DA neurons and induces their insertion in the NAc, potentially modulating synaptic plasticity by altering the contribution of GluA2 to AMPARs.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Konstantinos Toskas, Behzad Yaghmaeian-Salmani, Olga Skiteva, Wojciech Paslawski, Linda Gillberg, Vasiliki Skara, Irene Antoniou, Erik Sodersten, Per Svenningsson, Karima Chergui, Markus Ringner, Thomas Perlmann, Johan Holmberg
Summary: This study reveals that the maintenance of cellular identity in dopaminergic and serotonergic neurons relies on the Polycomb repressive complex 2 (PRC2). Loss of PRC2 leads to gene activation, impaired neuronal function, and disease phenotypes.
Article
Biochemistry & Molecular Biology
Giacomo Sitzia, Olga Skiteva, Karima Chergui
Summary: The study found that the neurophysiological and synaptic characteristics of LRRK2-G2019S mice remain largely unchanged, with subtle alterations in firing patterns and glutamatergic synaptic transmission in SNr neurons, indicating changes that occur before neurodegeneration in a late-onset PD model.
Article
Neurosciences
Olga Skiteva, Ning Yao, Ioannis Mantas, Xiaoqun Zhang, Thomas Perlmann, Per Svenningsson, Karima Chergui
Summary: In Parkinson's disease (PD), degeneration of dopaminergic (DA) neurons occurs in the substantia nigra pars compacta (SNc). This study investigated the function of voltage-gated calcium channels (VGCCs) in two different mouse models of PD. The findings revealed opposite changes in the contribution of T-type and L-type VGCCs in DA neuron somata, potentially linked to oxidative stress.
NPJ PARKINSONS DISEASE
(2023)
Article
Neurosciences
Mona Nouhi, Xiaoqun Zhang, Ning Yao, Karima Chergui
CNS NEUROSCIENCE & THERAPEUTICS
(2018)
Article
Neurosciences
Xiaoqun Zhang, Ning Yao, Karima Chergui
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)