Article
Behavioral Sciences
Bethany H. Dennis, Stuart A. Neale, Fiona E. N. LeBeau, Thomas E. Salt
Summary: Aberrant cortical oscillations in the beta and gamma range are associated with symptoms of schizophrenia and other psychiatric conditions. Activation of Group II mGlu receptors, and mGlu2 specifically, with orthosteric agonists reduced the power of both beta and gamma oscillations in ACC without a significant effect on oscillation peak frequencies.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
Article
Neurosciences
Cristina Delgado-Sallent, Pau Nebot, Thomas Gener, Amanda B. Fath, Melina Timplalexi, M. Victoria Puig
Summary: Neural synchrony and functional connectivity are disrupted in schizophrenia. Atypical antipsychotic drugs, but not typical antipsychotic drugs, can reduce prefrontal and cortical-hippocampal hypersynchrony induced by psychosis-like states, suggesting that atypical antipsychotic drugs target prefrontal-hippocampal pathways for antipsychotic action. Serotonin receptors may play a selective role in the distinct effects of atypical antipsychotic drugs compared to typical antipsychotic drugs.
Article
Biochemistry & Molecular Biology
Samantha V. Abram, Brian J. Roach, Susanna L. Fryer, Vince D. Calhoun, Adrian Preda, Theo G. M. van Erp, Juan R. Bustillo, Kelvin O. Lim, Rachel L. Loewy, Barbara K. Stuart, John H. Krystal, Judith M. Ford, Daniel H. Mathalon
Summary: NMDAR hypofunction is a leading pathophysiological model of schizophrenia. Resting-state functional magnetic resonance imaging (rsfMRI) studies demonstrate thalamic dysconnectivity pattern in schizophrenia involving excessive connectivity with sensory regions and deficient connectivity with frontal, cerebellar, and thalamic regions. Ketamine, an NMDAR antagonist, induces schizophrenia-like symptoms and alters rsfMRI thalamic connectivity. This study confirms that ketamine-induced thalamic dysconnectivity resembles the thalamic dysconnectivity observed in schizophrenia, which suggests the contribution of NMDAR hypofunction to the pathophysiology of schizophrenia.
MOLECULAR PSYCHIATRY
(2022)
Article
Neurosciences
Cynthia Kwan, Imane Frouni, Stephen G. Nuara, Sebastien Belliveau, Woojin Kang, Adjia Hamadjida, Dominique Bedard, Francis Beaudry, Michel Panisset, Jim C. Gourdon, Philippe Huot
Summary: The study demonstrated that concurrent antagonising of 5-HT2A and activation of mGlu(2) receptors could provide greater anti-dyskinetic and anti-psychotic effects than either approach alone. Additionally, mGlu(2) activation may enhance the therapeutic effects of 5-HT2A blockade, potentially offering relief beyond current therapies for PD patients with dyskinesia and psychotic symptoms.
Article
Biochemistry & Molecular Biology
Joanna M. Wieronska, Paulina Cieslik, Grzegorz Burnat, Leszek Kalinowski
Summary: The Morris water maze (MWM) is a popular test for spatial memory in rodents. Activators for muscarinic and metabotropic glutamate receptors can prevent cognitive disorders induced by MK-801 in the MWM. MWM learning increases cGMP synthesis in the cortex and hippocampi, which can be reversed by high doses of the investigated compounds.
Article
Pharmacology & Pharmacy
Kwang-Hyun Hur, Seong-Eon Kim, Shi-Xun Ma, Bo-Ram Lee, Yong-Hyun Ko, Jee-Yeon Seo, Seon-Kyung Kim, Young-Jung Kim, Su-Jeong Sung, Youyoung Lee, Young Hoon Jung, Yong-Sup Lee, Seok-Yong Lee, Choon-Gon Jang
Summary: The study demonstrates that methoxphenidine exhibits addictive and schizophrenia-like behaviors, inducing neurochemical changes in brain regions associated with these behaviors. These findings suggest that methoxphenidine could be utilized in developing animal disease models and calls for legal restrictions on its recreational use.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Daniel C. Javitt
Summary: Cognitive impairment is a prominent feature of schizophrenia, and its assessment methods are well established. The role of social cognitive impairment and sensory-level dysfunction in functional outcomes has also been recognized. Treatment development targeting N-methyl-d-aspartate receptor (NMDAR) and its associated impairments has become encouraging. Mismatch negativity has emerged as a promising biomarker for early-stage drug development in schizophrenia.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Review
Neurosciences
Qiongqiong Wu, Jing Huang, Renrong Wu
Summary: The NMDAR hypofunction hypothesis offers a new perspective for treating negative symptoms and cognitive dysfunction in schizophrenia, with drugs targeting this receptor showing promise in improving symptoms. However, unsatisfactory outcomes in clinical studies suggest further research is needed to effectively utilize this hypothesis.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
Alasdair J. Gibb
Summary: NMDA receptors, specifically the triheteromeric structure of GluN1/GluN2B/GluN2D receptors, play fundamental roles in synaptic physiology and have implications for pharmacological research. This study reviews the mechanism of action of drugs targeting allosteric antagonists at these receptors.
Article
Psychiatry
Anne S. Mallien, Natascha Pfeiffer, Miriam A. Vogt, Sabine Chourbaji, Rolf Sprengel, Peter Gass, Dragos Inta
Summary: Extensive evidence suggests dysfunction of NMDAR in schizophrenia may be related to early neurodevelopment, but clinical symptoms appear during late adolescence. NMDAR blockade/hypofunction can also trigger psychosis in adulthood without early neurodevelopmental issues. Deletion of NMDAR in late adolescence does not induce behavioral abnormalities resembling psychiatric disorders, indicating other neuronal substrates may underlie post-adolescent NMDAR-driven psychosis.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Lisa Klotz, Ralf Enz
Summary: The study analyzed the expression and localization of mGluR7a and mGluR7b in mouse cochlear wholemounts, finding a presynaptic localization of mGluR7a at inner hair cells (IHCs) and co-localization of mGluR7b with mGluR7a at IHC ribbon synapses. The numbers of mGluR7a and mGluR7b puncta were reduced at higher frequencies and in older animals, indicating potential age and frequency-related changes in the cochlea.
Article
Neurosciences
Deborah K. Park, Samuel Petshow, Margarita Anisimova, Eden V. Barragan, John A. Gray, Ivar S. Stein, Karen Zito
Summary: This study shows that decreased D-serine levels associated with schizophrenia enhance ion flux-independent NMDAR signaling, leading to destabilized dendritic spines. This hypothesis was tested using the serine racemase knockout mouse model and the results support the hypothesis.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Chitra Vinnakota, Matthew R. R. Hudson, Nigel C. C. Jones, Suresh Sundram, Rachel A. A. Hill
Summary: Glutamate N-methyl-D-aspartate receptor (NMDAR) hypofunction is believed to be responsible for schizophrenia symptoms. Among the NMDAR subunits, the GluN2D subunit is implicated in schizophrenia-related phenotypes, and further research into this subunit may lead to novel therapeutic targets for the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Psychiatry
Kasumi Yasuda, Shinya Uenishi, Hiroshi Sakamoto, Kohei Hori, Jinsoo Koh, Shun Takahashi
Summary: This article presents a case of a woman diagnosed with schizophrenia without antiNMDAR antibodies after experiencing NMDAR encephalitis. The study suggests that NMDAR dysfunction may be associated with the onset of schizophrenia.
ASIAN JOURNAL OF PSYCHIATRY
(2022)
Review
Biochemistry & Molecular Biology
Deepa Gautam, Ulhas P. Naik, Meghna U. Naik, Santosh K. Yadav, Rameshwar Nath Chaurasia, Debabrata Dash
Summary: This paper explores the role of platelets in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, as well as the critical role of glutamate receptors in the pathophysiology of these diseases. By reviewing data from clinical trials, animal models, and cellular studies, it reveals the involvement of glutamate receptor dysfunction in neurodegenerative processes and provides an overview of current treatments, including glutamate receptor antagonists, for AD and PD.
Article
Clinical Neurology
Andrew McCarthy, Sally Loomis, Brian Eastwood, Keith A. Wafford, Raphaelle Winsky-Sommerer, Gary Gilmour
JOURNAL OF SLEEP RESEARCH
(2017)
Article
Neurosciences
Nicholas W. Johnson, Mazhar Ozkan, Adrian P. Burgess, Emma J. Prokic, Keith A. Wafford, Michael J. O'Neill, Stuart D. Greenhill, Ian M. Stanford, Gavin L. Woodhall
Review
Neurosciences
Christian M. Wood, Celine S. Nicolas, Sun-Lim Choi, Erika Roman, Ingrid Nylander, Alberto Fernandez-Teruel, Kalervo Kiianmaa, Przemyslaw Bienkowski, Trynke R. de Jong, Giancarlo Colombo, Denis Chastagnier, Keith A. Wafford, Graham L. Collingridge, Sheryl J. Wildt, Becky L. Conway-Campbell, Emma S. J. Robinson, David Lodge
Article
Neurosciences
Laura E. McKillop, Simon P. Fisher, Nanyi Cui, Stuart N. Peirson, Russell G. Foster, Keith A. Wafford, Vladyslav V. Vyazovskiy
JOURNAL OF NEUROSCIENCE
(2018)
Article
Neurosciences
Robert F. Bruns, Stephen N. Mitchell, Keith A. Wafford, Alex J. Harper, Elaine A. Shanks, Guy Carter, Michael J. O'Neill, Tracey K. Murray, Brian J. Eastwood, John M. Schaus, James P. Beck, Junliang Hao, Jeffrey M. Witkin, Xia Li, Eyassu Chernet, Jason S. Katner, Hong Wang, John W. Ryder, Meghane E. Masquelin, Linda K. Thompson, Patrick L. Love, Deanna L. Maren, Julie F. Falcone, Michelle M. Menezes, Linli Zhang, Charles R. Yang, Kjell A. Svensson
Article
Neurosciences
Christian M. Wood, Keith A. Wafford, Andrew P. McCarthy, Nicola Hewes, Elaine Shanks, David Lodge, Emma S. J. Robinson
Article
Behavioral Sciences
Raphaelle Winsky-Sommerer, Paula de Oliveira, Sally Loomis, Keith Wafford, Derk-Jan Dijk, Gary Gilmour
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2019)
Article
Multidisciplinary Sciences
Mathieu Nollet, Harriet Hicks, Andrew P. McCarthy, Huihai Wu, Carla S. Moller-Levet, Emma E. Laing, Karim Malki, Nathan Lawless, Keith A. Wafford, Derk-Jan Dijk, Raphaelle Winsky-Sommerer
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Clinical Neurology
Nicola Hanley, Jerome Paulissen, Brian J. Eastwood, Gary Gilmour, Sally Loomis, Keith A. Wafford, Andrew McCarthy
Article
Clinical Neurology
C. M. Holton, N. Hanley, E. Shanks, P. Oxley, A. McCarthy, B. J. Eastwood, T. K. Murray, A. Nickerson, K. A. Wafford
ALZHEIMERS RESEARCH & THERAPY
(2020)
Article
Neurosciences
Caterina Montani, Carola Canella, Adam J. Schwarz, Jennifer Li, Gary Gilmour, Alberto Galbusera, Keith Wafford, Daniel Gutierrez-Barragan, Andrew McCarthy, David Shaw, Karen Knitowski, David McKinzie, Alessandro Gozzi, Christian Felder
Summary: The cholinergic drug xanomeline, acting at M1/M4 muscarinic receptors, induces widespread functional activity changes in the rodent brain, including decreased connectivity in the neocortex and striatum, and increased functional connectivity within the nucleus accumbens. Moreover, its effects on phencyclidine and ketamine suggest a modulatory role in specific functional networks within the brain.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Andrew P. McCarthy, Kjell A. Svensson, Elaine Shanks, Claire Brittain, Brian J. Eastwood, William Kielbasa, Kevin M. Biglan, Keith A. Wafford
Summary: This study provides the first translational evidence of the effects of a selective dopamine receptor 1 positive allosteric modulator (D1PAM) on sleep and wakefulness in both humanized dopamine receptor 1 mice and sleep-deprived healthy male volunteers. The findings suggest that sleep-wake activity can serve as a translational biomarker for D1PAM and that D1PAMs may have therapeutic potential for sleep disorders and excessive daytime sleepiness associated with neurodegenerative disorders.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Neurosciences
Paula de Oliveira, Claire Cella, Nicolas Locker, Kiran K. G. Ravindran, Agampodi Mendis, Keith Wafford, Gary Gilmour, Derk-Jan Dijk, Raphaelle Winsky-Sommerer
Summary: This study investigated the effects of trazodone on cellular pathways and behavioral features of tauopathies in mice. The results showed that trazodone reduced neuroinflammation and unfolded protein response, improved sleep quality and memory performance. These findings provide preliminary evidence for the potential therapeutic value of sleep-modulating compounds in the treatment of tauopathies.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Georgios Drakakis, Keith A. Wafford, Suzanne C. Brewerton, Michael J. Bodkin, David A. Evans, Andreas Bender
ACS CHEMICAL BIOLOGY
(2017)
Correction
Neurosciences
Lucia Privitera, Ellen L. Hogg, Matthias Gaestel, Mark J. Wall, Sonia A. L. Correa
Article
Neurosciences
Li-Ya Jiang, Guan-Hao Wang, Jing-Jiao Xu, Xiao-Li Li, Xiao-Yan Lin, Xiang Fang, Hong-Xu Zhang, Mei Feng, Chun-Ming Jiang
Summary: This study reveals the importance of LINC00473 in regulating temozolomide (TMZ) resistance in glioblastoma (GB) and its potential mechanism. By regulating the expression of CEBP alpha and MGMT, LINC00473 promotes the formation of chemoresistance. Furthermore, LINC00473 can transfer chemoresistance to adjacent sensitive cells through exosomes.
Article
Neurosciences
Olga Kopach, Tetyana Pivneva, Nataliya Fedirko, Nana Voitenko
Summary: This study found that diabetic animals exhibit severe xerostomia characterized by reduced saliva flow rate, diminished total protein content, and decreased amylase activity. The impaired saliva production in diabetes is associated with reduced and delayed intracellular Ca2+ signals in submandibular acinar cells, caused by malfunctioning mitochondria. Targeting malfunctioning mitochondria may be a potential strategy for the treatment of diabetic xerostomia.
Article
Neurosciences
Nicholas M. Timme, Cherish E. Ardinger, Seth D. C. Weir, Rachel Zelaya-Escobar, Rachel Kruger, Christopher C. Lapish
Summary: This study aimed to assess aversion-resistant drinking behavior in head-fixed mice and explore the relationship between non-consummatory behaviors and aversion-resistant drinking. The results showed that head-fixed mice exhibited heterogenous levels of aversion-resistant drinking and non-consummatory behaviors were related to the intensity of this behavior.
Article
Neurosciences
David R. Maguire, Charles P. France
Summary: Methocinnamox (MCAM) is a novel, long-acting opioid receptor antagonist that effectively decreases fentanyl self-administration and prevents opioid overdose in monkeys. The study demonstrates the potential therapeutic utility of MCAM in the treatment of opioid use disorder.
Article
Neurosciences
Xiang Li, Dan Feng, Shenglu Ma, Mingxing Li, Shulei Zhao, Man Tang
Summary: This study investigated the effects of fluoxetine on neurochemical, neurobiological, and neurobehavioral changes in different subregions of the hippocampus. The results showed that fluoxetine increased dialysate 5-HT, decreased membrane 5-HTT protein, and increased cytoplasmic fraction. Additionally, fluoxetine reduced immobility times in behavioral tests, with greater effects observed in the ventral subregion compared to the dorsal subregion.
Article
Neurosciences
Alexander V. Zholos, Mariia I. Melnyk, Dariia O. Dryn
Summary: Acetylcholine is an important neurotransmitter in visceral smooth muscles, activating M2 and M3 muscarinic receptors to cause smooth muscle excitation and contraction. This review focuses on the cellular and molecular mechanisms underlying acetylcholine-induced depolarisation and smooth muscle contraction, as well as the effects of anticholinergic drugs on gastrointestinal motility. The knowledge gained from recent studies has greatly expanded our understanding of these processes.
Article
Neurosciences
Zhenlong Li, Hsien-Yu Peng, Chau-Shoun Lee, Tzer-Bin Lin, Ming-Chun Hsieh, Cheng-Yuan Lai, Han-Fang Wu, Lih-Chyang Chen, Mei-Ci Chen, Dylan Chou
Summary: Methylone shows significant efficacy in treating depression and social deficits, making it an ideal candidate for anti-depressant medication.
Article
Neurosciences
Aline Freyssin, Allison Carles, Sarra Guehairia, Gilles Rubinstenn, Tangui Maurice
Summary: This study explores the potential of combining FENM and S1R agonists in the treatment of Alzheimer's disease. The results showed that most FENM-based combinations can protect against learning deficits caused by A beta 25-35, with better efficacy in short-term memory.
Article
Neurosciences
J. D. Lorente, J. Cuitavi, L. Rullo, S. Candeletti, P. Romualdi, L. Hipolito
Summary: This study analyzed the effects of pain on negative affect in different sexes and time courses, as well as the involvement of the dynorphinergic and corticotropin releasing factor systems in these pain-related behaviors. The results showed sex and time-dependent anxiety- and anhedonia-like behaviors induced by pain in female rats. The recruitment of KOR/DYN in the NAc was identified as a key neurological substrate mediating pain-induced behavioral alterations.
Article
Neurosciences
Rongjun Liu, Daofan Sun, Xiuzhong Xing, Qingge Chen, Bo Lu, Bo Meng, Hui Yuan, Lan Mo, Liufang Sheng, Jinwei Zheng, Qiusheng Wang, Junping Chen, Xiaowei Chen
Summary: The coexistence of pain and depression is frequently observed in patients with chronic pain and depression. Oxytocin, a neuropeptide, has been reported to relieve chronic pain and depressive symptoms. This study investigated the effect of intranasal oxytocin on neuropathic pain and comorbid depressive symptoms, and found that oxytocin attenuated depression-like behavior but did not alleviate mechanical hyperalgesia. The results suggest that intranasal oxytocin may have the potential to treat depressive symptoms in neuropathic pain patients.