During embryonic development, expression of neurotrophin receptor tyrosine kinases (Trks) by sensory ganglia is continuously and dynamically regulated. Neurotrophin signaling promotes selective survival and axonal differentiation of sensory neurons. In embryonic day (E) 15 rat trigeminal ganglion (TG), NGF receptor TrkA is expressed by small diameter neurons, NT-3 receptor TrkC and BDNF receptor TrkB are expressed by large diameter neurons. Organotypic explant and dissociated cell cultures of the TG (and dorsal root ganglia) are commonly used to assay neurotrophin effects on developing sensory neurons. In this study, we compared Trk expression in E15 rat TG explant and dissociated cell cultures with or without neurotrophin treatment. Only a subset of TG cells express each of the three Trk receptors in wholemount explant cultures as in vivo conditions. In contrast, all TG neurons co-express all three Trk receptors upon dissociation, regardless of neurotrophin treatment. Neurons cultured in low concentrations of one neurotrophin first, and switched to higher concentrations of another after 1 day, survive and display morphological characteristics of neurons cultured in a mixture of both neurotrophins for 3 days. Our results indicate that wholemount explant cultures of sensory ganglia represent in vivo conditions in terms of Trk expression patterns; whereas dissociation dramatically alters Trk expression by primary sensory neurons.
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http://dx.doi.org/10.1002/neu.20134 | DOI Listing |
Bio Protoc
January 2025
Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
Neurons are highly polarized cells, with axons that may innervate distant target regions. In the brain, basal forebrain cholinergic neurons (BFCNs) possess extensive axons that project to several target regions such as the cortex, hippocampus, and amygdala, and may be exposed to a specific microenvironment in their axon targets that may have retrograde effects on neuronal health. Interestingly, BFCNs express the pan-neurotrophin receptor p75NTR throughout life while also concomitantly co-expressing all Trk receptors, making them capable of responding to both mature and precursor neurotrophins to promote survival or apoptosis, respectively.
View Article and Find Full Text PDFBr J Anaesth
December 2024
Department of Anesthesiology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China. Electronic address:
Background: Recent studies have implicated a role for perioperative medications in determining patient outcomes after surgery for malignant tumours, including relapse and metastasis.
Methods: A combined approach spanned molecular, cellular, and organismal levels, including bioinformatics, immunohistochemical staining of clinical and animal samples, RNA sequencing of glioblastoma multiforme (GBM) cells with Ingenuity Pathway Analysis, lentiviral-mediated gene expression modulation, in vitro cell experiments, and in vivo orthotopic tumour transplantation.
Results: We observed a significant correlation between increased kappa opioid receptor (KOP receptor) expression and better prognosis in patients with glioma.
Oncologist
December 2024
The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW 2010, Australia.
Background: TRK-inhibitors have demonstrated efficacy across several cancers with NTRK fusions. Their activity in cancers with NTRK overexpression remains unclear.
Methods: This trial enrolled patients with advanced cancers harboring NTRK fusions or extreme mRNA overexpression, defined as NTRK1/2/3 expression by RNA profiling >5 SDs for a given cancer type.
Elife
December 2024
Birmingham Centre for Neurogenetics, School of Biosciences, University of Birmingham, Birmingham, United Kingdom.
Experience shapes the brain as neural circuits can be modified by neural stimulation or the lack of it. The molecular mechanisms underlying structural circuit plasticity and how plasticity modifies behaviour are poorly understood. Subjective experience requires dopamine, a neuromodulator that assigns a value to stimuli, and it also controls behaviour, including locomotion, learning, and memory.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Otorhinolaryngology, Medical University Innsbruck, 6020 Innsbruck, Austria.
We determined the relative expression levels of the receptors , , , and and ligands , , , and with RNAseq analysis on fetal human inner ear samples, located TrkB and TrkC proteins, and quantified with in situ hybridization on histological sections between gestational weeks (GW) 9 to 19. Spiral ganglion neurons (SGNs) and satellite glia appear to be the main source of and synthesis peaks twice at GW10 and GW15-GW17. Tonotopical gradients of revert between GW8 and GW15 and follow a maturation and innervation density gradient in SGNs.
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