Brainstem nuclei serve a diverse array of functions in many of which ionotropic glutamate receptors are known to be involved. However, little detailed information is available on the expression of different glutamate receptor subunits in specific nuclei. We used RT-PCR in mice to analyze the glutamate receptor subunit composition of the pre-Bötzinger complex, the hypoglossal nucleus, the nucleus of the solitary tract, and the inferior olive. Analyzing 15 receptor subunits and five variants, we found all four alpha-amino-3-hydroxy-5-methyl-4-propionic acid (AMPA) and six NMDA receptor (NR) subunits as well as three of five kainate (KA) receptors (GluR5, GluR6, and KA1) to be expressed in all nuclei. However, some distinct differences were observed: The inferior olive preferentially expresses flop variants of AMPA receptors, GluR7 is more abundant in the pre-Bötzinger complex than in the other nuclei, and NR2C is most prominent in the nucleus of the solitary tract. In single hypoglossal motoneurons and interneurons of the pre-Bötzinger complex investigation of GluR2 editing revealed strong expression of the GluR2-R editing variant, suggesting low Ca2+ permeability of AMPA receptors. Thus, Ca2+-permeable AMPA receptors are unlikely to be the cause for the reported selective vulnerability of hypoglossal motoneurons during excitotoxic events.
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http://dx.doi.org/10.1046/j.1471-4159.2000.0741335.x | DOI Listing |
Chem Biodivers
January 2025
UNIFESSPA: Universidade Federal do Sul e Sudeste do Para, Faculdade de Psicologia, Rod. BR-230 (Transamazônica), Loteamento Cidade Jardim, Av. dos Ipês, s/n.º - Ci, 68503000, Marabá, BRAZIL.
Chrysin (5,7-dihydroxyflavone) is a natural flavonoid with potential anxiolytic-like effects in preclinical models. Acute treatment with this molecule (0 - 10 mg/kg) produced a biphasic dose-response in the zebrafish light/dark test (LDT), with anxiolytic-like effect at low doses and anxiogenic-like effects at high doses. Chrysin (1 mg/kg) decreased anxiety-like behavior in the zebrafish novel tank test (NTT), but did not prevent the anxiogenic effects of acute stress.
View Article and Find Full Text PDFHemasphere
January 2025
Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, UNSW Centre for Childhood Cancer Research UNSW Sydney Sydney New South Wales Australia.
Antibody-drug conjugates (ADCs) combining monoclonal antibodies with cytotoxic payloads are a rapidly emerging class of immune-based therapeutics with the potential to improve the treatment of cancer, including children with relapse/refractory acute lymphoblastic leukemia (ALL). CD123, the α subunit of the interleukin-3 receptor, is overexpressed in ALL and is a potential therapeutic target. Here, we show that pivekimab sunirine (PVEK), a recently developed ADC comprising the CD123-targeting antibody, G4723A, and the cytotoxic payload, DGN549, was highly effective in vivo against a large panel of pediatric ALL patient-derived xenograft (PDX) models ( = 39).
View Article and Find Full Text PDFThe GPCR-like protein Smoothened (Smo) plays a pivotal role in the Hedgehog (Hh) pathway. To initiate Hh signaling, active Smo binds to and inhibits the catalytic subunit of PKA in the primary cilium, a process facilitated by G protein-coupled receptor kinase 2 (Grk2). However, the precise regulatory mechanisms underlying this process, as well as the events preceding and following Smo activation, remain poorly understood.
View Article and Find Full Text PDFGlia
January 2025
Department of Neurobiology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Microglia, the parenchymal macrophage of the central nervous system, serve crucial remodeling functions throughout development. Microglia are transcriptionally heterogenous, suggesting that distinct microglial states confer discrete roles. Currently, little is known about how dynamic these states are, the cues that promote them, or how they impact microglial function.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
January 2025
Department of Biology and Biotechnologies "Charles Darwin", Sapienza University, 00185, Rome, Italy.
Background: Metabolic syndrome represents a pancreatic ductal adenocarcinoma (PDAC) risk factor. Metabolic alterations favor PDAC onset, which occurs early upon dysmetabolism. Pancreatic neoplastic lesions evolve within a dense desmoplastic stroma, consisting in abundant extracellular matrix settled by cancer associated fibroblasts (CAFs).
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