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Involvement of CX3CL1/CX3CR1 signaling in spinal long term potentiation.

Bian C, Zhao ZQ, Zhang YQ, Lü N - PLoS ONE (2015)

Bottom Line: Exogenous CX3CL1 significantly potentiated 3-trains TSS-induced LTP in rats.Consistently, spinal LTP of C-fiber-evoked field potentials was also induced by TSS (100 Hz, 1s, 4 trains) in all C57BL/6 wild type (WT) mice.These results suggest that CX3CL1/CX3CR1 signaling is involved in LTP of C-fiber-evoked field potentials in the rodent spinal dorsal horn.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.

ABSTRACT
The long-term potentiation (LTP) of spinal C-fiber-evoked field potentials is considered as a fundamental mechanism of central sensitization in the spinal cord. Accumulating evidence has showed the contribution of spinal microglia to spinal LTP and pathological pain. As a key signaling of neurons-microglia interactions, the involvement of CX3CL1/CX3CR1 signaling in pathological pain has also been investigated extensively. The present study examined whether CX3CL1/CX3CR1 signaling plays a role in spinal LTP. The results showed that 10-trains tetanic stimulation (100 Hz, 2s) of the sciatic nerve (TSS) produced a significant LTP of C-fiber-evoked field potentials lasting for over 3 h in the rat spinal dorsal horn. Blockade of CX3CL1/CX3CR1 signaling with an anti-CX3CR1 neutralizing antibody (CX3CR1 AB) markedly suppressed TSS-induced LTP. Exogenous CX3CL1 significantly potentiated 3-trains TSS-induced LTP in rats. Consistently, spinal LTP of C-fiber-evoked field potentials was also induced by TSS (100 Hz, 1s, 4 trains) in all C57BL/6 wild type (WT) mice. However, in CX3CR1-/- mice, TSS failed to induce LTP and behavioral hypersensitivity, confirming an essential role of CX3CR1 in spinal LTP induction. Furthermore, blockade of IL-18 or IL-23, the potential downstream factors of CX3CL1/CX3CR1 signaling, with IL-18 BP or anti-IL-23 neutralizing antibody (IL-23 AB), obviously suppressed spinal LTP in rats. These results suggest that CX3CL1/CX3CR1 signaling is involved in LTP of C-fiber-evoked field potentials in the rodent spinal dorsal horn.

No MeSH data available.


Related in: MedlinePlus

Expression of CX3CL1 and CX3CR1 in the spinal dorsal horn.Double immunofluorescence reveals that CX3CL1 co-localized with NeuN (neuronal marker) and GFAP (astrocyte marker), no immunoreactive singal in Iba1-labled microglia (A); CX3CR1 was expressed in Iba1-labled microglia in naïve rats and failed to co-localize with NeuN and GFAP (B).
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pone.0118842.g001: Expression of CX3CL1 and CX3CR1 in the spinal dorsal horn.Double immunofluorescence reveals that CX3CL1 co-localized with NeuN (neuronal marker) and GFAP (astrocyte marker), no immunoreactive singal in Iba1-labled microglia (A); CX3CR1 was expressed in Iba1-labled microglia in naïve rats and failed to co-localize with NeuN and GFAP (B).

Mentions: Double immunostaining was performed on sections of the L4–6 spinal cord in rats. The distributions of CX3CL1 and CX3CR1 were examined in the spinal dorsal horn of naïve rats. Consistent with previous reports [21, 30], CX3CL1 was mostly expressed in NeuN (neuron marker)-labeled neuron and slightly in GFAP (astrocytic marker)-labeled cells in the spinal cord (Fig. 1A). Its receptor, CX3CR1 was mainly colocalized with Iba1 (microglia marker) (Fig. 1B).


Involvement of CX3CL1/CX3CR1 signaling in spinal long term potentiation.

Bian C, Zhao ZQ, Zhang YQ, Lü N - PLoS ONE (2015)

Expression of CX3CL1 and CX3CR1 in the spinal dorsal horn.Double immunofluorescence reveals that CX3CL1 co-localized with NeuN (neuronal marker) and GFAP (astrocyte marker), no immunoreactive singal in Iba1-labled microglia (A); CX3CR1 was expressed in Iba1-labled microglia in naïve rats and failed to co-localize with NeuN and GFAP (B).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358970&req=5

pone.0118842.g001: Expression of CX3CL1 and CX3CR1 in the spinal dorsal horn.Double immunofluorescence reveals that CX3CL1 co-localized with NeuN (neuronal marker) and GFAP (astrocyte marker), no immunoreactive singal in Iba1-labled microglia (A); CX3CR1 was expressed in Iba1-labled microglia in naïve rats and failed to co-localize with NeuN and GFAP (B).
Mentions: Double immunostaining was performed on sections of the L4–6 spinal cord in rats. The distributions of CX3CL1 and CX3CR1 were examined in the spinal dorsal horn of naïve rats. Consistent with previous reports [21, 30], CX3CL1 was mostly expressed in NeuN (neuron marker)-labeled neuron and slightly in GFAP (astrocytic marker)-labeled cells in the spinal cord (Fig. 1A). Its receptor, CX3CR1 was mainly colocalized with Iba1 (microglia marker) (Fig. 1B).

Bottom Line: Exogenous CX3CL1 significantly potentiated 3-trains TSS-induced LTP in rats.Consistently, spinal LTP of C-fiber-evoked field potentials was also induced by TSS (100 Hz, 1s, 4 trains) in all C57BL/6 wild type (WT) mice.These results suggest that CX3CL1/CX3CR1 signaling is involved in LTP of C-fiber-evoked field potentials in the rodent spinal dorsal horn.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China.

ABSTRACT
The long-term potentiation (LTP) of spinal C-fiber-evoked field potentials is considered as a fundamental mechanism of central sensitization in the spinal cord. Accumulating evidence has showed the contribution of spinal microglia to spinal LTP and pathological pain. As a key signaling of neurons-microglia interactions, the involvement of CX3CL1/CX3CR1 signaling in pathological pain has also been investigated extensively. The present study examined whether CX3CL1/CX3CR1 signaling plays a role in spinal LTP. The results showed that 10-trains tetanic stimulation (100 Hz, 2s) of the sciatic nerve (TSS) produced a significant LTP of C-fiber-evoked field potentials lasting for over 3 h in the rat spinal dorsal horn. Blockade of CX3CL1/CX3CR1 signaling with an anti-CX3CR1 neutralizing antibody (CX3CR1 AB) markedly suppressed TSS-induced LTP. Exogenous CX3CL1 significantly potentiated 3-trains TSS-induced LTP in rats. Consistently, spinal LTP of C-fiber-evoked field potentials was also induced by TSS (100 Hz, 1s, 4 trains) in all C57BL/6 wild type (WT) mice. However, in CX3CR1-/- mice, TSS failed to induce LTP and behavioral hypersensitivity, confirming an essential role of CX3CR1 in spinal LTP induction. Furthermore, blockade of IL-18 or IL-23, the potential downstream factors of CX3CL1/CX3CR1 signaling, with IL-18 BP or anti-IL-23 neutralizing antibody (IL-23 AB), obviously suppressed spinal LTP in rats. These results suggest that CX3CL1/CX3CR1 signaling is involved in LTP of C-fiber-evoked field potentials in the rodent spinal dorsal horn.

No MeSH data available.


Related in: MedlinePlus