Article
Biochemistry & Molecular Biology
Alma Hrnjadovic, James Friedmann, Sandra Barhebreus, Patricia J. Allen, Bernat Kocsis
Summary: The study aimed to investigate the role of 5-HT7 receptors in the reversal learning component of ASST and found that 5-HT7 receptor antagonist could reverse the impaired performance induced by NMDA receptor blockade, particularly affecting the reversal phases of ASST.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Hikaru Koizumi, Taichi Hiraga, Leandro K. Oharomari, Toshiaki Hata, Takeru Shima, Jang Soo Yook, Masahiro Okamoto, Akihiro Mouri, Toshitaka Nabeshima, Hideaki Soya
Summary: Schizophrenia may be attributed to perinatal neurodevelopmental deficits and influenced by environmental factors. Hypofrontality and dysfunction in glutamatergic and dopaminergic neurons are known factors, while early enriched environment and low-intensity exercise training during adolescence may help prevent and ameliorate the disease.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell Biology
Brittney Yegla, Asha Rani, Ashok Kumar
Summary: Age-associated decrease in NMDAR-mediated synaptic function contributes to cognitive impairments. Enhancing NMDAR function via increased SR expression in middle age rats improves learning and synaptic transmission. Prefrontal SR upregulation can improve visual discrimination and increase NMDAR activity.
Article
Neurosciences
Patrick R. Melugin, Fei Wu, Crystal Munoz, Aarron Phensy, Grishma Pradhan, Yi Luo, Abraham Nofal, Rohan Manepalli, Sven Kroener
Summary: Alcohol use disorder is associated with changes in the medial prefrontal cortex, including altered glutamatergic transmission and deficits in executive functions. Acamprosate can reduce alcohol craving and relapse by improving alcohol-induced dysregulation of glutamatergic signaling. This study found that acamprosate and its active moiety calcium can improve deficits in cognitive flexibility and altered glutamatergic signaling in mice that self-administered alcohol under goal-directed conditions. However, under conditions that bias behavior towards habitual responding, the effects of acamprosate and calcium on glutamatergic transmission were not observed.
Article
Neurosciences
Joseph A. McQuail, Sofia Beas, Kyle B. Kelly, Caesar M. Hernandez, Jennifer L. Bizon, Charles J. Frazier
Summary: The study revealed that loss of NMDARs on interneurons in the PFC contributes to age-related impairment of cognitive flexibility, while a clear increase in AMPA/NMDA ratio in FSIs suggests a potential underlying mechanism for cognitive decline. These findings provide new insights into the neural mechanisms of cognitive decline.
Article
Neurosciences
Hristo Varbanov, Shaobo Jia, Gaga Kochlamazashvili, Subhrajit Bhattacharya, Manal Ali Buabeid, Mohamed El Tabbal, Hussam Hayani, Stoyan Stoyanov, Weilun Sun, Hauke Thiesler, Iris Roeckle, Herbert Hildebrandt, Oleg Senkov, Vishnu Suppiramaniam, Rita Gerardy-Schahn, Alexander Dityatev
Summary: Dysregulated cortical expression of NCAM and deficits of its associated polySia are found in Alzheimer's disease and schizophrenia. Acute enzymatic removal of polySia in the prefrontal cortex leads to increased transmission mediated by GluN1/GluN2B NMDARs, impaired LTP, and increased tonic currents. Treatment with polySia fragments or inhibition of GluN1/GluN2B receptors restores LTP and cognitive tasks in polySia-deficient mice and Alzheimer's disease models. The data highlight the crucial role of polySia-NCAM in balancing signaling through synaptic/extrasynaptic NMDARs and the therapeutic potential of polySia fragments.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Psychiatry
Shengtao Yang, Hyojung Seo, Min Wang, Amy F. T. Arnsten
Summary: The dlPFC generates mental representations through NMDAR transmission, while disruptions can lead to cognitive deficits. AMPAR plays a crucial role in visual stimuli and sensory event responses, whereas NMDAR is important for affective and visceral responses.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Psychiatry
Hagar Bauminger, Hiba Zaidan, Irit Akirav, Inna Gaisler-Salomon
Summary: NMDA receptor blockade in rodents can induce schizophrenia-like behavioral abnormalities, and the endocannabinoid system can modulate these abnormalities. The study shows that anandamide hydrolysis inhibitor can reverse the behavioral deficits induced by NMDA receptor blocker in adolescence. It also suggests that endocannabinoid stimulation may have therapeutic potential in treating treatment-resistant symptoms.
SCHIZOPHRENIA BULLETIN
(2022)
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
Anatomy & Morphology
Elizabeth Woo, Dibyadeep Datta, Amy F. T. Arnsten
Summary: mGlu3 receptors are mainly expressed in neurons and astrocytes in rat PL mPFC, and are also found in microglia to a lesser extent. They are predominantly located on axons and widely distributed in the glial membrane, but are also present on dendritic spines, particularly in layer III.
FRONTIERS IN NEUROANATOMY
(2022)
Article
Biochemistry & Molecular Biology
Carolina Wilnerzon Thorn, Vasilios Kafetzopoulos, Bernat Kocsis
Summary: The Dopamine D4 receptor (D4R) mechanisms are implicated in psychiatric diseases characterized by cognitive deficits. This study found that D4R activation enhances slow rhythm in the prefrontal cortex (PFC) and suppresses theta rhythm in the hippocampus (HPC), while D4R antagonists have the opposite effect.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Psychiatry
Tiziana Imbriglio, Marika Alborghetti, Valeria Bruno, Giuseppe Battaglia, Ferdinando Nicoletti, Milena Cannella
Summary: The study found that TAAR1 mRNA levels were increased in the SCZ prefrontal cortex, with no correlation to various factors. Differences in TAAR1 protein levels were observed between neuropathological burden subgroups of CTRL, but not within the SCZ group. TAAR1 protein levels were lower in CTRL with low neuropathological burden compared to all SCZ samples or SCZ samples with low neuropathological burden. In the SCZ group, TAAR1 protein levels were inversely correlated with duration of antipsychotic treatment and higher in individuals treated with second-generation antipsychotics.
SCHIZOPHRENIA BULLETIN
(2023)
Article
Neurosciences
Somdatta Saha, Javier Gonzalez-Maeso
Summary: Schizophrenia is a severe brain disorder that often leads to lifelong disability. First and second-generation antipsychotic medications are currently the standard treatment for schizophrenia. While antipsychotics can effectively alleviate positive symptoms in some patients, they are ineffective in treating cognitive deficits and may even cause small improvements or deterioration. This highlights the need for innovative and more efficient therapeutic targets for schizophrenia treatment.
Article
Pharmacology & Pharmacy
Congwu Du, Yueming Hua, Kevin Clare, Kicheon Park, Craig P. Allen, Nora D. Volkow, Xiu-Ti Hu, Yingtian Pan
Summary: Individuals with substance use disorder are at a higher risk of contracting HIV and progressing to AIDS. Neurotoxicity and neurodegeneration are characteristic of HIV-1-associated neurocognitive disorders. Studies have found that cocaine potentiates the neurotoxic effects of HIV-associated proteins. The NMDA antagonist drug memantine shows potential in attenuating the neurotoxicity caused by cocaine and HIV.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Edison Leung, Ethan W. Lau, Andi Liang, Constanza de Dios, Robert Suchting, Linda Ostlundh, Joseph C. Masdeu, Masahiro Fujita, Marsal Sanches, Jair C. Soares, Sudhakar Selvaraj
Summary: This study systematically reviews the pathophysiological mechanisms of bipolar and major depressive disorders, focusing on synaptic proteins and RNA alterations. Meta-analysis results indicate specific changes in synaptic proteins and RNAs in both disorders, although conflicting results are observed due to small sample sizes and variations in data sources.
MOLECULAR PSYCHIATRY
(2022)