Article
Multidisciplinary Sciences
Ji-Woon Kim, Joachim Herz, Ege T. Kavalali, Lisa M. Monteggia
Summary: This study investigated whether disruptions in Reelin-mediated synaptic signaling alter ketamine-triggered synaptic plasticity and behavioral effects. The findings suggest that impairments in Reelin-Apoer2-SFK pathway components may in part underlie nonresponsiveness to ketamine's antidepressant action.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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
Psychiatry
Uzma Zahid, Robert A. A. McCutcheon, Faith Borgan, Sameer Jauhar, Fiona Pepper, Matthew M. M. Nour, Maria Rogdaki, Martin Osugo, Graham K. K. Murray, Pamela Hathway, Robin M. M. Murray, Oliver D. D. Howes
Summary: This study found that baseline glutamatergic levels are unlikely to predict treatment response in patients with first episode psychosis. Antipsychotic treatment also does not significantly affect glutamate levels in the anterior cingulate cortex.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Rebecca M. Woods, Jarred M. Lorusso, Isabella Harris, Hager M. Kowash, Christopher Murgatroyd, Joanna C. Neill, Jocelyn D. Glazier, Michael Harte, Reinmar Hager
Summary: Exposure to maternal immune activation (MIA) in utero increases the risk of neurodevelopmental disorders. The study investigates the relationship between MIA and cognitive deficits by focusing on Reelin signalling in the brain. The findings suggest that dysregulation of Reelin signalling due to MIA contributes to cognitive deficits through altered NMDA receptor function.
Article
Behavioral Sciences
Carla L. Sanchez-Lafuente, Raquel Romay-Tallon, Josh Allen, Jenessa N. Johnston, Lisa E. Kalynchuk, Hector J. Caruncho
Summary: This study reveals the sexually dimorphic subpopulation of reelin-positive neurons in the paraventricular nucleus that can be differentially affected by chronic stress for the first time. Chronic corticosterone shows gender-specific effects on behavior and reelin expression in the paraventricular nucleus.
HORMONES AND BEHAVIOR
(2022)
Article
Endocrinology & Metabolism
Chao Wang, Yaqiong An, Zhaohua Xia, Xuezhi Zhou, Haibo Li, Shuang Song, Lexi Ding, Xiaobo Xia
Summary: This study found that melatonin could protect RGCs from glutamate excitotoxicity and NMDA-induced injury, reduce oxidative stress, and improve visual function in mice. These findings provide practical research ideas for the comprehensive prevention and treatment of glaucoma using melatonin.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Neurosciences
Sebastiano A. Torrisi, Silvia Rizzo, Samuele Laudani, Alessandro Ieraci, Filippo Drago, Gian Marco Leggio
Summary: Several studies have shown that chronic stress has a negative effect on recognition memory, but the effects of acute stress on this cognitive ability have not been well studied. This study aimed to investigate the impact of acute stress on recognition memory consolidation in a sex-dependent manner. The results showed that acute stress did not affect memory performance in male and female mice immediately after training, but it altered memory performance after a 24-hour delay, with sex-dependent effects.
NEUROBIOLOGY OF STRESS
(2023)
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
Neurosciences
S. Murat Durakoglugil, R. Catherine Wasser, H. Connie Wong, Theresa Pohlkamp, Xunde Xian, Courtney Lane-Donovan, Katja Fritschle, Lea Naestle, Joachim Herz
Summary: Alzheimer's disease is characterized by the accumulation of Aβ plaques and neurofibrillary tangles, leading to synaptic dysfunction. Reelin protects synapses against Aβ toxicity through ApoE receptors. Experiments showed that Reelin modulates mGluR-LTD, potentially impacting memory consolidation or neurodegeneration.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Amit Kumar, Ansab Akhtar, Anurag Kuhad, Sangeeta Pilkhwal Sah
Summary: This study found that sarcosine can alleviate the behavioral symptoms of schizophrenia by modulating oxidative stress, neuroinflammation, and mitochondrial dysfunction.
EXPERIMENTAL BRAIN RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Nina Treder, Albert Martinez-Pinteno, Natalia Rodriguez, Nestor Arbelo, Santiago Madero, Marta Gomez, Clemente Garcia-Rizo, Sergi Mas, Patricia Gasso, Eduard Parellada, Constanza Moren
Summary: Schizophrenia is a heterogeneous mental disorder that affects approximately 1% of the global population. One of the main pathophysiological theories suggests an imbalance between excitatory glutamatergic pyramidal neurons and inhibitory GABAergic interneurons, involving N-methyl-D-aspartate receptors (NMDAr). This imbalance may lead to excessive glutamate storms, dendritic pruning, and cellular stress, including nitrosative stress mediated by nitric oxide (NO). The administration of NMDAr antagonists has been found to increase nitric oxide synthase (NOS) levels in specific brain regions, suggesting a potential target for early treatments. In a murine model, the protein levels of NOS were analyzed in the prefrontal cortex (PFC) and ventral hippocampus (HPC) after ketamine-induced schizophrenia, as well as after treatment with clozapine (CLZ) or JNJ-46356479 (JNJ). The findings suggest a dysregulation of the NOS system following NMDAr antagonist administration, which can be modulated by early CLZ and JNJ treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Environmental Sciences
Mohsen Shamsi, Maliheh Soodi, Shirin Shahbazi, Ameneh Omidi
Summary: The study found that Acetamiprid reduces glutamate levels, affects the expression of NMDA receptor subunits in the hippocampus, leading to impaired memory consolidation at low doses, and loss of neural cells in the dentate gyrus area at high doses.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2021)
Article
Clinical Neurology
Kah Kheng Goh, Tzu-Hua Wu, Chun-Hsin Chen, Mong-Liang Lu
Summary: In patients with schizophrenia, N-methyl-D-aspartate receptor modulator supplements, when used in conjunction with antipsychotic medications, can improve certain symptoms, particularly negative symptoms, with satisfactory side effects and safety profiles.
JOURNAL OF PSYCHOPHARMACOLOGY
(2021)
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
Biochemistry & Molecular Biology
David W. Greening, Michael Notaras, Maoshan Chen, Rong Xu, Joel D. Smith, Lesley Cheng, Richard J. Simpson, Andrew F. Hill, Maarten van den Buuse
Summary: Studies have shown that chronic Meth abuse can lead to psychotic episodes resembling schizophrenia, with Brain-derived neurotrophic factor (BDNF) playing a crucial role in this process. Research on transgenic mice revealed that BDNF genetic variation significantly influences the long-term brain changes induced by Meth, indicating that drug-induced psychosis may be modulated at the molecular level by a single genetic locus.
MOLECULAR PSYCHIATRY
(2021)
Article
Neurosciences
Laura K. Milton, Paul N. Mirabella, Erika Greaves, David C. Spanswick, Maarten van den Buuse, Brian J. Oldfield, Claire J. Foldi
Summary: This study investigated the neurobiological link between pathological weight loss and cognitive flexibility, showing that modulation of activity within the mPFC-AcbSh pathway can prevent weight loss in ABA and improve cognitive flexibility. This finding highlights the relationship between disrupted prefrontal function and cognitive rigidity in AN patients, providing insight into the executive control of feeding behavior and potential new treatment strategies.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Immunology
Jay P. Nakamura, Brendan Gillespie, Andrew Gibbons, Emily J. Jaehne, Xin Du, Aaron Chan, Anna Schroeder, Maarten van den Buuse, Suresh Sundram, Rachel A. Hill
Summary: Research using a mouse MIA model has shown that targeting a specific developmental window of parvalbumin interneurons can enhance spatial working memory performance, independent of anxiety or novelty seeking behavior.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Neurosciences
Maarten van den Buuse, Paul Halley, Gerard F. Hoyne
Summary: The hypomorphic allele of hnRNPLL gene affects immune system and brain function, and the mice model for psychiatric illnesses exhibit behaviors related to depression, impaired spatial memory, and reduced avoidance learning.
NEUROSCIENCE LETTERS
(2021)
Article
Behavioral Sciences
Natasha L. Hogan, Emily J. Jaehne, Sharon Bak, Elvan Djouma, Maarten van den Buuse
Summary: Impulsivity may be a potential predictor of addiction risk, while the BDNFVal66Met polymorphism may sex-specifically alter aspects of impulsive behavior and addiction propensity.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Neurosciences
Stephanie C. Tran, Emily J. Jaehne, Laura E. Dye, Joanne Wong, Jana S. Bakas, Jemma G. Gasperoni, Matthew W. Hale, Maarten van den Buuse, Sebastian Dworkin, Sylvia V. H. Grommen, Bert De Groef
Summary: Plag1 gene deficiency in mice has mild effects on behavior, with no significant differences in circadian activity levels, locomotion, object recognition, spatial memory, or sociability compared to wild-type mice. However, tests suggest that Plag1 KO mice may have a hearing impairment, indicating a potential role in auditory processes.
Article
Neurosciences
Michelle Corrone, Aleshia Nanev, Isabella Amato, Rowena Bicknell, Daniel William Taylor Wundersitz, Maarten van den Buuse, Bradley James Wright
Summary: This study investigated the impact of the val66met gene on decision making and attention, revealing that carriers of the Val/met genotype performed better in these aspects. They also exhibited higher levels of perceived chronic stress and increased sympathetic activity.
Article
Behavioral Sciences
Emily J. Jaehne, Elaine Mei San Chong, Alyssa Sbisa, Brendan Gillespie, Rachel Hill, Andrea Gogos, Maarten van den Buuse
Summary: The study suggests that in offspring of maternal immune activation (MIA), the TrkB agonist 7,8-DHF can reverse PPI deficits caused by dopaminergic stimulation, possibly through the increased expression of BDNF in the frontal cortex. Targeting BDNF signaling may have therapeutic potential for treating certain symptoms of schizophrenia.
BEHAVIOURAL PHARMACOLOGY
(2021)
Article
Psychiatry
Andrea Gogos, Jeehae Sun, Madhara Udawela, Andrew Gibbons, Maarten van den Buuse, Elizabeth Scarr, Brian Dean
Summary: The study found alterations in RAPGEF1 expression in the BA 8 of subjects with schizophrenia, but no differences in BA 8 and 44. Suicide completers had higher RAPGEF1 levels compared to non-suicide schizophrenia subjects in BA 8. Further investigation into the function of RAPGEF1 may provide insights into the pathophysiology of schizophrenia.
PSYCHIATRY RESEARCH
(2021)
Article
Neurosciences
Mauricio Sepulveda, Elizabeth E. Manning, Andrea Gogos, Matthew Hale, Maarten van den Buuse
Summary: This study evaluated the long-term effects of chronic METH treatment on the serotonin system in the brain using various techniques. The results indicated that METH treatment can lead to long-term or selective effects on brain serotonin systems. METH pretreatment may affect 5-HT1A receptor binding and reduce DRN cell counts selectively in BDNF HET mice.
Article
Biology
Carla L. Pietrucci, Laura K. Milton, Erika Greaves, Aneta Stefanidis, Maarten van den Buuse, Brian J. Oldfield, Claire J. Foldi
Summary: Genetic animal models are a valuable tool for understanding human pathologies, with the choice of model being crucial for uncovering specific effects. Contrary to previous findings in mice, the BDNF Val66Met polymorphism does not appear to influence susceptibility to weight loss or energy balance in a rat model of anorexia nervosa. These discrepancies highlight the importance of considering species-specific differences in research on animal models of human diseases.
Article
Developmental Biology
Emily J. Jaehne, Jessica N. Kent, Nikki Lam, Lina Schonfeld, Jereme G. Spiers, Veronica Begni, Federico De Rosa, Marco A. Riva, Maarten van den Buuse
Summary: Exercise has been shown to be beneficial in reducing symptoms of affective disorders and increasing BDNF expression. This study found that rats that had access to running wheels during adolescence exhibited higher levels of anxiety and depression-like behaviors in adulthood, regardless of their BDNF Val66Met genotype.
DEVELOPMENTAL PSYCHOBIOLOGY
(2023)
Article
Neurosciences
Matthew R. Hudson, Joshua Foreman, Gil Rind, Elizabeth E. Manning, Nigel C. Jones, Maarten van den Buuse
Summary: Chronic METH treatment does not affect the regulation of high-frequency neuronal oscillations in the brain, despite causing behavioral sensitization.
Article
Biology
Emily J. Jaehne, Elizabeth McInerney, Ronan Sharma, Shannyn G. Genders, Elvan Djouma, Maarten van den Buuse
Summary: The Val66Met gene variant reduces the release of BDNF in the brain, leading to decreased preference and seeking for alcohol. Using a rat model, researchers found that rats with the Met/Met genotype had lower motivation to seek alcohol and a decreased propensity to relapse. This suggests a possible protective effect of the Met/Met genotype against alcohol use disorder, particularly in females.
Article
Biochemistry & Molecular Biology
Samuel Hogarth, Emily J. Jaehne, Xiangjun Xu, Quenten Schwarz, Maarten van den Buuse
Summary: The aim of this study was to investigate the role of BDNF and dopamine D3 receptors in the effects of chronic methamphetamine on prepulse inhibition (PPI), an endophenotype of psychosis. The results showed that chronic methamphetamine disrupted PPI regulation in male mice with BDNF haploinsufficiency, regardless of D3 receptor knockout. However, there were no effects of BDNF heterozygosity or D3 knockout on PPI regulation in female mice. These findings suggest a significant involvement of BDNF in the long-term effects of methamphetamine on PPI, particularly in male mice.