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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

Contribution of IL-18 and IL-23 to spinal LTP.(A & B) In the spinal cord, IL-18 was mainly produced in Iba1-labled microglia and co-localized with CX3CR1 (A); both IL-18R and IL-23 were expressed in astrocytes (B). (C) As compared with control (PBS, 0.01M 30 μl), the spinal LTP was obviously suppressed by administrating IL-18BP (7 μg/30 μl) 20 min before 10-trains TSS. (D) Similarly, the spinal LTP was also suppressed by an anti-IL-23 neutralizing antibody (IL-23 AB, 6 μg/30 μl), which was administrated 40 min before 10-trains TSS.
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pone.0118842.g005: Contribution of IL-18 and IL-23 to spinal LTP.(A & B) In the spinal cord, IL-18 was mainly produced in Iba1-labled microglia and co-localized with CX3CR1 (A); both IL-18R and IL-23 were expressed in astrocytes (B). (C) As compared with control (PBS, 0.01M 30 μl), the spinal LTP was obviously suppressed by administrating IL-18BP (7 μg/30 μl) 20 min before 10-trains TSS. (D) Similarly, the spinal LTP was also suppressed by an anti-IL-23 neutralizing antibody (IL-23 AB, 6 μg/30 μl), which was administrated 40 min before 10-trains TSS.

Mentions: Double immunostaining showed that in the spinal cord CX3CR1 colocalized with IL-18 that predominately expressed in spinal microglia in rats. In addition, IL-18 receptor and IL-23 were both mainly expressed in astrocytes in the spinal dorsal horn (Fig. 5A and B). We therefore examined the influences of IL-18 and IL-23 on rat spinal LTP. As shown in Fig. 5C and D, Spinal application of IL-18 BP (7.0 μg/30 μl) or anti-IL-23 antibody (IL-23 AB, 6.0 μg/30 μl) for 20 min (IL-18BP) or 40 min (IL-23 AB) before TSS significantly suppressed the spinal LTP of C-fiber-evoked field potential (Two-way ANOVA, IL-18BP treatments: F1, 13 = 10.485, p < 0.01; IL-23AB treatments: F1, 10 = 21.741) (Fig. 5C, D).


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

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

Contribution of IL-18 and IL-23 to spinal LTP.(A & B) In the spinal cord, IL-18 was mainly produced in Iba1-labled microglia and co-localized with CX3CR1 (A); both IL-18R and IL-23 were expressed in astrocytes (B). (C) As compared with control (PBS, 0.01M 30 μl), the spinal LTP was obviously suppressed by administrating IL-18BP (7 μg/30 μl) 20 min before 10-trains TSS. (D) Similarly, the spinal LTP was also suppressed by an anti-IL-23 neutralizing antibody (IL-23 AB, 6 μg/30 μl), which was administrated 40 min before 10-trains TSS.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0118842.g005: Contribution of IL-18 and IL-23 to spinal LTP.(A & B) In the spinal cord, IL-18 was mainly produced in Iba1-labled microglia and co-localized with CX3CR1 (A); both IL-18R and IL-23 were expressed in astrocytes (B). (C) As compared with control (PBS, 0.01M 30 μl), the spinal LTP was obviously suppressed by administrating IL-18BP (7 μg/30 μl) 20 min before 10-trains TSS. (D) Similarly, the spinal LTP was also suppressed by an anti-IL-23 neutralizing antibody (IL-23 AB, 6 μg/30 μl), which was administrated 40 min before 10-trains TSS.
Mentions: Double immunostaining showed that in the spinal cord CX3CR1 colocalized with IL-18 that predominately expressed in spinal microglia in rats. In addition, IL-18 receptor and IL-23 were both mainly expressed in astrocytes in the spinal dorsal horn (Fig. 5A and B). We therefore examined the influences of IL-18 and IL-23 on rat spinal LTP. As shown in Fig. 5C and D, Spinal application of IL-18 BP (7.0 μg/30 μl) or anti-IL-23 antibody (IL-23 AB, 6.0 μg/30 μl) for 20 min (IL-18BP) or 40 min (IL-23 AB) before TSS significantly suppressed the spinal LTP of C-fiber-evoked field potential (Two-way ANOVA, IL-18BP treatments: F1, 13 = 10.485, p < 0.01; IL-23AB treatments: F1, 10 = 21.741) (Fig. 5C, D).

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