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  1. Article ; Online: Cell non-autonomous requirement of p75 in the development of geniculate oral sensory neurons

    Tao Tang / Christopher R. Donnelly / Amol A. Shah / Robert M. Bradley / Charlotte M. Mistretta / Brian A. Pierchala

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Abstract During development of the peripheral taste system, oral sensory neurons of the geniculate ganglion project via the chorda tympani nerve to innervate taste buds in fungiform papillae. Germline deletion of the p75 neurotrophin receptor causes ... ...

    Abstract Abstract During development of the peripheral taste system, oral sensory neurons of the geniculate ganglion project via the chorda tympani nerve to innervate taste buds in fungiform papillae. Germline deletion of the p75 neurotrophin receptor causes dramatic axon guidance and branching deficits, leading to a loss of geniculate neurons. To determine whether the developmental functions of p75 in geniculate neurons are cell autonomous, we deleted p75 specifically in Phox2b + oral sensory neurons (Phox2b-Cre; p75fx/fx) or in neural crest-derived cells (P0-Cre; p75fx/fx) and examined geniculate neuron development. In germline p75−/− mice half of all geniculate neurons were lost. The proportion of Phox2b + neurons, as compared to Phox2b-pinna-projecting neurons, was not altered, indicating that both populations were affected similarly. Chorda tympani nerve recordings demonstrated that p75−/− mice exhibit profound deficits in responses to taste and tactile stimuli. In contrast to p75−/− mice, there was no loss of geniculate neurons in either Phox2b-Cre; p75fx/fx or P0-Cre; p75fx/fx mice. Electrophysiological analyses demonstrated that Phox2b-Cre; p75fx/fx mice had normal taste and oral tactile responses. There was a modest but significant loss of fungiform taste buds in Phox2b-Cre; p75fx/fx mice, although there was not a loss of chemosensory innervation of the remaining fungiform taste buds. Overall, these data suggest that the developmental functions of p75 are largely cell non-autonomous and require p75 expression in other cell types of the chorda tympani circuit.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice

    Sangsu Bang / Christopher R. Donnelly / Xin Luo / Maria Toro-Moreno / Xueshu Tao / Zilong Wang / Sharat Chandra / Andrey V. Bortsov / Emily R. Derbyshire / Ru-Rong Ji

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 17

    Abstract: GPR37 is expressed in macrophages, and has been implicated in resolution of inflammatory pain. Here the authors show that GPR37 can modulate sepsis in several animal models. ...

    Abstract GPR37 is expressed in macrophages, and has been implicated in resolution of inflammatory pain. Here the authors show that GPR37 can modulate sepsis in several animal models.
    Keywords Science ; Q
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: STING suppresses bone cancer pain via immune and neuronal modulation

    Kaiyuan Wang / Christopher R. Donnelly / Changyu Jiang / Yihan Liao / Xin Luo / Xueshu Tao / Sangsu Bang / Aidan McGinnis / Michael Lee / Matthew J. Hilton / Ru-Rong Ji

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 21

    Abstract: There is an unmet clinical need to develop therapies to alleviate metastatic bone pain, frequently observed in patients with advanced cancers. Here, using mouse models of bone cancer pain, the authors show that STING agonists not only suppress bone ... ...

    Abstract There is an unmet clinical need to develop therapies to alleviate metastatic bone pain, frequently observed in patients with advanced cancers. Here, using mouse models of bone cancer pain, the authors show that STING agonists not only suppress bone cancer tumor burden, but also attenuate bone pain and reduce cancer-induced bone destruction.
    Keywords Science ; Q
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: PD-1 Regulates GABAergic Neurotransmission and GABA-Mediated Analgesia and Anesthesia

    Changyu Jiang / Zilong Wang / Christopher R. Donnelly / Kaiyuan Wang / Amanda S. Andriessen / Xueshu Tao / Megumi Matsuda / Junli Zhao / Ru-Rong Ji

    iScience, Vol 23, Iss 10, Pp 101570- (2020)

    2020  

    Abstract: Summary: The immune checkpoint inhibitor programmed cell death protein 1 (PD-1) plays a critical role in immune regulation. Recent studies have demonstrated functional PD-1 expression in peripheral sensory neurons, which contributes to neuronal ... ...

    Abstract Summary: The immune checkpoint inhibitor programmed cell death protein 1 (PD-1) plays a critical role in immune regulation. Recent studies have demonstrated functional PD-1 expression in peripheral sensory neurons, which contributes to neuronal excitability, pain, and opioid analgesia. Here we report neuronal expression and function of PD-1 in the central nervous system (CNS), including the spinal cord, thalamus, and cerebral cortex. Notably, GABA-induced currents in spinal dorsal horn neurons, thalamic neurons, and cortical neurons are suppressed by the PD-1-neutralizing immunotherapeutic Nivolumab in spinal cord slices, brain slices, and dissociated cortical neurons. Reductions in GABA-mediated currents in CNS neurons were also observed in Pd1−/− mice without changes in GABA receptor expression. Mechanistically, Nivolumab binds spinal cord neurons and elicits ERK phosphorylation to suppress GABA currents. Finally, both GABA-mediated analgesia and anesthesia are impaired by Pd1 deficiency. Our findings reveal PD-1 as a CNS-neuronal inhibitor that regulates GABAergic signaling and GABA-mediated behaviors.
    Keywords Immunology ; Molecular Biology ; Neuroscience ; Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by Potentiating Ret Signaling

    Zhijiang Chen / Christopher R. Donnelly / Bertha Dominguez / Yoshinobu Harada / Weichun Lin / Alan S. Halim / Tasha G. Bengoechea / Brian A. Pierchala / Kuo-Fen Lee

    Cell Reports, Vol 21, Iss 3, Pp 707-

    2017  Volume 720

    Abstract: Producing the neuronal diversity required to adequately discriminate all elements of somatosensation is a complex task during organogenesis. The mechanisms guiding this process during dorsal root ganglion (DRG) sensory neuron specification remain poorly ... ...

    Abstract Producing the neuronal diversity required to adequately discriminate all elements of somatosensation is a complex task during organogenesis. The mechanisms guiding this process during dorsal root ganglion (DRG) sensory neuron specification remain poorly understood. Here, we show that the p75 neurotrophin receptor interacts with Ret and its GFRα co-receptor upon stimulation with glial cell line-derived neurotrophic factor (GDNF). Furthermore, we demonstrate that p75 is required for GDNF-mediated Ret activation, survival, and cell surface localization of Ret in DRG neurons. In mice in which p75 is deleted specifically within sensory neurons beginning at E12.5, we observe that approximately 20% of neurons are lost between P14 and adulthood, and these losses selectively occur within a subpopulation of Ret+ nonpeptidergic nociceptors, with neurons expressing low levels of Ret impacted most heavily. These results suggest that p75 is required for the development of the nonpeptidergic nociceptor lineage by fine-tuning Ret-mediated trophic support.
    Keywords p75 ; Ret ; GDNF ; dorsal root ganglion ; nonpeptidergic ; nociceptive neuron ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2017-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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