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Fractalkine Attenuates Microglial Cell Activation Induced by Prenatal Stress.

Ślusarczyk J, Trojan E, Głombik K, Chamera K, Roman A, Budziszewska B, Basta-Kaim A - Neural Plast. (2016)

Bottom Line: Our study found that the microglia do not express fractalkine.In conclusion, the present results revealed that the pathological activation of microglia in prenatally stressed newborns may be attenuated by fractalkine administration.Therefore, understanding of the role of the CX3CL1-CX3CR1 system may help to elucidate the mechanisms underlying the neuron-microglia interaction and its role in pathological conditions in the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Krakow, Poland.

ABSTRACT
The potential contribution of inflammation to the development of neuropsychiatric diseases has recently received substantial attention. In the brain, the main immune cells are the microglia. As they are the main source of inflammatory factors, it is plausible that the regulation of their activation may be a potential therapeutic target. Fractalkine (CX3CL1) and its receptor CX3CR1 play a crucial role in the control of the biological activity of the microglia. In the present study, using microglial cultures we investigated whether fractalkine is able to reverse changes in microglia caused by a prenatal stress procedure. Our study found that the microglia do not express fractalkine. Prenatal stress decreases the expression of the fractalkine receptor, which in turn is enhanced by the administration of exogenous fractalkine. Moreover, treatment with fractalkine diminishes the prenatal stress-induced overproduction of proinflammatory factors such as IL-1β, IL-18, IL-6, TNF-α, CCL2, or NO in the microglial cells derived from prenatally stressed newborns. In conclusion, the present results revealed that the pathological activation of microglia in prenatally stressed newborns may be attenuated by fractalkine administration. Therefore, understanding of the role of the CX3CL1-CX3CR1 system may help to elucidate the mechanisms underlying the neuron-microglia interaction and its role in pathological conditions in the brain.

No MeSH data available.


Related in: MedlinePlus

Effect of fractalkine and anti-fractalkine receptor antibody on the prenatal stress-induced changes in CX3CR1 expression in the microglia cell cultures. The microglia obtained from the control and prenatally stressed rats were pretreated with anti-fractalkine receptor antibody for 1 h and then treated with fractalkine for 24 h. The levels of the CX3CR1 mRNA and protein were measured using qRT-PCR and Western blot analyses, respectively. The qRT-PCR data are shown as the average fold changes ± SEM. The Western blot data are shown as a % of the control ± SEM (the results are normalized to β-actin); P < 0.05; ∗ versus the control; # versus the stress group.
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fig6: Effect of fractalkine and anti-fractalkine receptor antibody on the prenatal stress-induced changes in CX3CR1 expression in the microglia cell cultures. The microglia obtained from the control and prenatally stressed rats were pretreated with anti-fractalkine receptor antibody for 1 h and then treated with fractalkine for 24 h. The levels of the CX3CR1 mRNA and protein were measured using qRT-PCR and Western blot analyses, respectively. The qRT-PCR data are shown as the average fold changes ± SEM. The Western blot data are shown as a % of the control ± SEM (the results are normalized to β-actin); P < 0.05; ∗ versus the control; # versus the stress group.

Mentions: Because the biological action of fractalkine is fulfilled through its receptor CX3CR1, we next evaluated the effect of prenatal stress on the levels of the CX3CR1 mRNA and protein. We demonstrated that the prenatal stress procedure significantly decreased the expression of the CX3CR1 mRNA (F1,39 = 16.62;  P < 0.05, Figure 6(a)) and protein (F1,44 = 10.22;  P < 0.05, Figure 6(b)). Interestingly, as demonstrated in post hoc test, the administration of exogenous fractalkine (200 ng/mL), the ligand for CX3CR1, normalized the prenatal stress-evoked decrease in the expression of the fractalkine receptor mRNA (P < 0.05, Figure 6(a)) and protein (P < 0.05, Figure 6(b)).


Fractalkine Attenuates Microglial Cell Activation Induced by Prenatal Stress.

Ślusarczyk J, Trojan E, Głombik K, Chamera K, Roman A, Budziszewska B, Basta-Kaim A - Neural Plast. (2016)

Effect of fractalkine and anti-fractalkine receptor antibody on the prenatal stress-induced changes in CX3CR1 expression in the microglia cell cultures. The microglia obtained from the control and prenatally stressed rats were pretreated with anti-fractalkine receptor antibody for 1 h and then treated with fractalkine for 24 h. The levels of the CX3CR1 mRNA and protein were measured using qRT-PCR and Western blot analyses, respectively. The qRT-PCR data are shown as the average fold changes ± SEM. The Western blot data are shown as a % of the control ± SEM (the results are normalized to β-actin); P < 0.05; ∗ versus the control; # versus the stress group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4863104&req=5

fig6: Effect of fractalkine and anti-fractalkine receptor antibody on the prenatal stress-induced changes in CX3CR1 expression in the microglia cell cultures. The microglia obtained from the control and prenatally stressed rats were pretreated with anti-fractalkine receptor antibody for 1 h and then treated with fractalkine for 24 h. The levels of the CX3CR1 mRNA and protein were measured using qRT-PCR and Western blot analyses, respectively. The qRT-PCR data are shown as the average fold changes ± SEM. The Western blot data are shown as a % of the control ± SEM (the results are normalized to β-actin); P < 0.05; ∗ versus the control; # versus the stress group.
Mentions: Because the biological action of fractalkine is fulfilled through its receptor CX3CR1, we next evaluated the effect of prenatal stress on the levels of the CX3CR1 mRNA and protein. We demonstrated that the prenatal stress procedure significantly decreased the expression of the CX3CR1 mRNA (F1,39 = 16.62;  P < 0.05, Figure 6(a)) and protein (F1,44 = 10.22;  P < 0.05, Figure 6(b)). Interestingly, as demonstrated in post hoc test, the administration of exogenous fractalkine (200 ng/mL), the ligand for CX3CR1, normalized the prenatal stress-evoked decrease in the expression of the fractalkine receptor mRNA (P < 0.05, Figure 6(a)) and protein (P < 0.05, Figure 6(b)).

Bottom Line: Our study found that the microglia do not express fractalkine.In conclusion, the present results revealed that the pathological activation of microglia in prenatally stressed newborns may be attenuated by fractalkine administration.Therefore, understanding of the role of the CX3CL1-CX3CR1 system may help to elucidate the mechanisms underlying the neuron-microglia interaction and its role in pathological conditions in the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Krakow, Poland.

ABSTRACT
The potential contribution of inflammation to the development of neuropsychiatric diseases has recently received substantial attention. In the brain, the main immune cells are the microglia. As they are the main source of inflammatory factors, it is plausible that the regulation of their activation may be a potential therapeutic target. Fractalkine (CX3CL1) and its receptor CX3CR1 play a crucial role in the control of the biological activity of the microglia. In the present study, using microglial cultures we investigated whether fractalkine is able to reverse changes in microglia caused by a prenatal stress procedure. Our study found that the microglia do not express fractalkine. Prenatal stress decreases the expression of the fractalkine receptor, which in turn is enhanced by the administration of exogenous fractalkine. Moreover, treatment with fractalkine diminishes the prenatal stress-induced overproduction of proinflammatory factors such as IL-1β, IL-18, IL-6, TNF-α, CCL2, or NO in the microglial cells derived from prenatally stressed newborns. In conclusion, the present results revealed that the pathological activation of microglia in prenatally stressed newborns may be attenuated by fractalkine administration. Therefore, understanding of the role of the CX3CL1-CX3CR1 system may help to elucidate the mechanisms underlying the neuron-microglia interaction and its role in pathological conditions in the brain.

No MeSH data available.


Related in: MedlinePlus