Cerebrospinal fluid-contacting nucleus mediates nociception via release of fractalkine

Zhou, Qinglong; Chen, S.S.; Zhang, Q.Q.; Liu, P.F.; Fang, Hong-Zhi; Yang, Yan; Zhang, L.C.

doi:10.1590/1414-431x20176275

Cited by 10 publications

(7 citation statements)

References 24 publications

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“…The CSF-contacting nucleus participates in pain modulation (Wang et al, 2014 ; Liu et al, 2017 ; Zhou et al, 2017 ), and it receives several pain-related regions in the subcortex and limbic system. The MS and diagonal band complex is crucial for information processing and chronic pain behavior (Jiang et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Novel Projections to the Cerebrospinal Fluid-Contacting Nucleus From the Subcortex and Limbic System in Rat

et al. 2020

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Objective: To identify the novel projections received by the cerebrospinal fluid (CSF)contacting nucleus from the subcortex and limbic system to understand the biological functions of the nucleus. Methods: The cholera toxin subunit B (CB), a retrograde tracer, was injected into the CSF-contacting nucleus in Sprague-Dawley rats. After 7-10 days, the surviving rats were perfused, and the whole brain and spinal cord were sliced for CB immunofluorescence detection. The CB-positive neurons in the subcortex and limbic system were observed under a fluorescence microscope, followed by 3D reconstructed with the imaris software. Results: CB-positive neurons were found in the basal forebrain, septum, periventricular organs, preoptic area, and amygdaloid structures. Five functional areas including 46 sub-regions sent projections to the CSF-contacting nucleus. However, the projections had different densities, ranging from sparse to moderate, to dense. Conclusions: According to the projections from the subcortex and limbic system, we hypothesize that the CSF-contacting nucleus participates in emotion, cognition, homeostasis regulation, visceral activity, pain, and addiction. In this study, we illustrate the novel projections from the subcortex and limbic system to the CSF-contacting nucleus, which underlies the diverse and complicated circuits of the nucleus in body regulations.

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Section: Discussionmentioning

confidence: 99%

Novel Projections to the Cerebrospinal Fluid-Contacting Nucleus From the Subcortex and Limbic System in Rat

et al. 2020

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“…The CSF-contacting nucleus is believed to be a unique nucleus in the brain that participates in neuron-neuron and neuron-body fluid crosstalk, and thus possibly influences the regulation of multiple physiological processes [23][24][25][26]. Increasing evidence also suggests that the CSF-contacting nucleus mediates the transduction and regulation of pain signals and might be involved in the modulation of the descending inhibitory system [27][28][29]. However, the precise molecular mechanisms remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats

Zubrzycki

Zubrzycka

Wysiadecki

et al. 2022

CIMB

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The endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) caused by the peripheral administration of the FAAH inhibitor URB597 and tooth pulp stimulation would affect the transmission of impulses between the sensory and motor centers localized in the vicinity of the third and fourth cerebral ventricles. The study objectives were evaluated on rats using a method that allowed the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation and URB597 treatment. The amplitude of ETJ was a measure of the effect of endocannabinoids on the neural structures. The concentrations of the endocannabinoids tested (AEA and 2-AG) were determined in the CSF, along with the expression of the cannabinoid receptors (CB1 and CB2) in the tissues of the mesencephalon, thalamus, and hypothalamus. We demonstrated that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was significantly increased in the CSF after treatment with a FAAH inhibitor, while tooth pulp stimulation had no effect on the AEA and 2-AG concentrations in the CSF. We also found positive correlations between the CSF AEA concentration and cannabinoid receptor type 1 (CB1R) expression in the brain, and between 2-AG and cannabinoid receptor type 2 (CB2R), and negative correlations between the CSF concentration of AEA and brain CB2R expression, and between 2-AG and CB1R. Our study shows that endogenous AEA, which diffuses through the cerebroventricular ependyma into CSF and exerts a modulatory effect mediated by CB1Rs, alters the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve. In addition, our findings may be consistent with the emerging concept that AEA and 2-AG have different regulatory mechanisms because they are involved differently in orofacial pain. We also suggest that FAAH inhibition may offer a therapeutic approach to the treatment of orofacial pain.

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“…The enzyme 6-phosphofructo-2-kinase/fructose-2,6,-bisphophatase 3 (PFKFB3) is commonly overexpressed in cancer where it promotes angiogenesis, migration, and proliferation [ 20 , 21 , 22 ]. More recent studies have shown the involvement of cytoplasmic PFKFB3 in response to DNA-damaging cisplatin in cervical cancer cells [ 23 ] and UV damage in primary mouse embryonic fibroblast [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

PFKFB3 Inhibition Sensitizes DNA Crosslinking Chemotherapies by Suppressing Fanconi Anemia Repair

Ninou

Lehto

Chioureas

et al. 2021

Cancers

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Replicative repair of interstrand crosslinks (ICL) generated by platinum chemotherapeutics is orchestrated by the Fanconi anemia (FA) repair pathway to ensure resolution of stalled replication forks and the maintenance of genomic integrity. Here, we identify novel regulation of FA repair by the cancer-associated glycolytic enzyme PFKFB3 that has functional consequences for replication-associated ICL repair and cancer cell survival. Inhibition of PFKFB3 displays a cancer-specific synergy with platinum compounds in blocking cell viability and restores sensitivity in treatment-resistant models. Notably, the synergies are associated with DNA-damage-induced chromatin association of PFKFB3 upon cancer transformation, which further increases upon platinum resistance. FA pathway activation triggers the PFKFB3 assembly into nuclear foci in an ATR- and FANCM-dependent manner. Blocking PFKFB3 activity disrupts the assembly of key FA repair factors and consequently prevents fork restart. This results in an incapacity to replicate cells to progress through S-phase, an accumulation of DNA damage in replicating cells, and fork collapse. We further validate PFKFB3-dependent regulation of FA repair in ex vivo cultures from cancer patients. Collectively, targeting PFKFB3 opens up therapeutic possibilities to improve the efficacy of ICL-inducing cancer treatments.

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Cerebrospinal fluid-contacting nucleus mediates nociception via release of fractalkine

Cited by 10 publications

References 24 publications

Novel Projections to the Cerebrospinal Fluid-Contacting Nucleus From the Subcortex and Limbic System in Rat

Novel Projections to the Cerebrospinal Fluid-Contacting Nucleus From the Subcortex and Limbic System in Rat

Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats

PFKFB3 Inhibition Sensitizes DNA Crosslinking Chemotherapies by Suppressing Fanconi Anemia Repair

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