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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.


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Involvement of CX3CR1 in spinal LTP.(A & B) When an anti-CX3CR1 neutralizing antibody (CX3CR1 AB, 30 μg/30 μl) was administrated 2 h before TSS, 10-trains TSS-induced spinal LTP was evidently suppressed (A). Simultaneously, the expression of CX3CR1 in spinal dorsal horn was also decreased by CX3CR1 AB (B). * p<0.05 vs. IgG control. (C) TSS stably induced spinal LTP of C-fiber-evoked field potentials in wild type mice, but failed to induce in CX3CL1 knockout mice. (D & E) TSS-induced mechanical allodynia (D) and thermal hyperalgesia (E) only occurred in wild type mice but not in CX3CL1 knockout mice. ** p>0.01 vs. Baseline (before TSS).
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pone.0118842.g003: Involvement of CX3CR1 in spinal LTP.(A & B) When an anti-CX3CR1 neutralizing antibody (CX3CR1 AB, 30 μg/30 μl) was administrated 2 h before TSS, 10-trains TSS-induced spinal LTP was evidently suppressed (A). Simultaneously, the expression of CX3CR1 in spinal dorsal horn was also decreased by CX3CR1 AB (B). * p<0.05 vs. IgG control. (C) TSS stably induced spinal LTP of C-fiber-evoked field potentials in wild type mice, but failed to induce in CX3CL1 knockout mice. (D & E) TSS-induced mechanical allodynia (D) and thermal hyperalgesia (E) only occurred in wild type mice but not in CX3CL1 knockout mice. ** p>0.01 vs. Baseline (before TSS).

Mentions: To examine whether CX3CL1/CX3CR1 signaling is involved in the spinal LTP, an anti-CX3CR1 neutralizing antibody (CX3CR1 AB)was applied to block CX3CL1/CX3CR1 signaling. As shown in Fig. 3A, the induction of spinal LTP was remarkably blocked by administration of CX3CR1 AB (30 μg/30 μl) 2h before 10-trains TSS, compared with control IgG (Two-way ANOVA, treatments: F1, 12 = 11.981, p<0.01). In addition, at the end of electrophysiological recording (3 h after TSS), the spinal dorsal horns were removed and the expression of CX3CR1 was examined by Western blots. Although no striking upregulation of CX3CR1 was observed after TSS, the expression of CX3CR1 was significantly decreased by delivering CX3CR1 AB, as compared with IgG (One-way ANOVA, F2, 9 = 5.399, p < 0.01) (Fig. 3B).


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

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

Involvement of CX3CR1 in spinal LTP.(A & B) When an anti-CX3CR1 neutralizing antibody (CX3CR1 AB, 30 μg/30 μl) was administrated 2 h before TSS, 10-trains TSS-induced spinal LTP was evidently suppressed (A). Simultaneously, the expression of CX3CR1 in spinal dorsal horn was also decreased by CX3CR1 AB (B). * p<0.05 vs. IgG control. (C) TSS stably induced spinal LTP of C-fiber-evoked field potentials in wild type mice, but failed to induce in CX3CL1 knockout mice. (D & E) TSS-induced mechanical allodynia (D) and thermal hyperalgesia (E) only occurred in wild type mice but not in CX3CL1 knockout mice. ** p>0.01 vs. Baseline (before TSS).
© Copyright Policy
Related In: Results  -  Collection

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pone.0118842.g003: Involvement of CX3CR1 in spinal LTP.(A & B) When an anti-CX3CR1 neutralizing antibody (CX3CR1 AB, 30 μg/30 μl) was administrated 2 h before TSS, 10-trains TSS-induced spinal LTP was evidently suppressed (A). Simultaneously, the expression of CX3CR1 in spinal dorsal horn was also decreased by CX3CR1 AB (B). * p<0.05 vs. IgG control. (C) TSS stably induced spinal LTP of C-fiber-evoked field potentials in wild type mice, but failed to induce in CX3CL1 knockout mice. (D & E) TSS-induced mechanical allodynia (D) and thermal hyperalgesia (E) only occurred in wild type mice but not in CX3CL1 knockout mice. ** p>0.01 vs. Baseline (before TSS).
Mentions: To examine whether CX3CL1/CX3CR1 signaling is involved in the spinal LTP, an anti-CX3CR1 neutralizing antibody (CX3CR1 AB)was applied to block CX3CL1/CX3CR1 signaling. As shown in Fig. 3A, the induction of spinal LTP was remarkably blocked by administration of CX3CR1 AB (30 μg/30 μl) 2h before 10-trains TSS, compared with control IgG (Two-way ANOVA, treatments: F1, 12 = 11.981, p<0.01). In addition, at the end of electrophysiological recording (3 h after TSS), the spinal dorsal horns were removed and the expression of CX3CR1 was examined by Western blots. Although no striking upregulation of CX3CR1 was observed after TSS, the expression of CX3CR1 was significantly decreased by delivering CX3CR1 AB, as compared with IgG (One-way ANOVA, F2, 9 = 5.399, p < 0.01) (Fig. 3B).

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