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Thrombin-induced kynurenine 3-monooxygenase causes variations in the kynurenine pathway, leading to neurological deficits in a murine intracerebral hemorrhage model.
J Pharmacol Sci
February 2025
Department of Physical Chemistry for Bioactive Molecules, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan.
The purpose of the present study is to investigate changes in the kynurenine pathway after intracerebral hemorrhage (ICH) and its effects on ICH-induced injury. The exposure of a primary rat microglial culture to thrombin increased the mRNA level of kynurenine 3-monooxygenase (KMO), and this increase was attenuated by a p38 MAPK inhibitor. Thrombin also increased the protein level of KMO.
View Article and Find Full Text PDFNon-ionotropic NMDAR signalling activates Panx1 to induce P2X4R-dependent long-term depression in the hippocampus.
J Physiol
December 2024
Department of Cell Biology & Anatomy, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
In recent years, evidence supporting non-ionotropic signalling by the NMDA receptor (niNMDAR) has emerged, including roles in long-term depression (LTD). Here, we investigated whether niNMDAR-pannexin-1 (Panx1) contributes to LTD at the CA3-CA1 hippocampal synapse. Using whole-cell, patch clamp electrophysiology in rat hippocampal slices, we show that a low-frequency stimulation (3 Hz) of the Schaffer collaterals produces LTD that is blocked by continuous but not transient application of the NMDAR competitive antagonist, MK-801.
View Article and Find Full Text PDFSpinal antinociceptive effect of the PnTx4(5-5) peptide is possibly mediated by the NMDA autoreceptors.
J Venom Anim Toxins Incl Trop Dis
November 2024
Department of Pharmacy, Federal University of Ouro Preto (UFOP), Ouro Preto, MG, Brazil.
Background: Medications currently used to treat pain are frequently associated with serious adverse effects and rapid development of tolerance. Thus, there is a need to develop more effective, and safer medicines for the population. Blocking NMDA receptors (NMDAR) has shown to be a promising target for the development of new drugs.
View Article and Find Full Text PDFEPO Deficiency Upregulates GADD45b/p38 MAPK Axis, Mediating Schizophrenia-Related Synaptic and Cognitive Impairments.
Adv Sci (Weinh)
December 2024
Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Schizophrenia (SZ) is a chronic and severe mental illness associated with psychiatric symptoms, cognitive deficits, and social dysfunction. Current clinical interventions only limit relief of psychiatric symptoms and have minimal impact on cognitive impairments. Erythropoietin (EPO), known for its role in neurogenesis and synaptic plasticity, is significantly low in SZ patients.
View Article and Find Full Text PDFMetabotropic NMDAR Signaling Contributes to Sex Differences in Synaptic Plasticity and Episodic Memory.
J Neurosci
December 2024
Departments of Anatomy and Neurobiology, University of California, Irvine, California 92697
NMDA receptor (NMDAR)-mediated calcium influx triggers the induction and initial expression of long-term potentiation (LTP). Here we report that in male rodents, ion flux-independent (metabotropic) NMDAR signaling is critical for a third step in the production of enduring LTP, i.e.
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