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Activation of sphingosine 1-phosphate receptor-1 by SEW2871 improves cognitive function in Alzheimer's disease model rats.

Asle-Rousta M, Oryan S, Ahmadiani A, Rahnema M - EXCLI J (2013)

Bottom Line: Upon Western Blot data bilateral intrahippocampal injection of Aβ1-42 decreased the expression of S1PR1 while increased S1PR2 level and did not affect that of S1PR3.We found that chronic administration of SEW2871 inhibited the reduction of S1PR1 expression and ameliorated spatial memory impairment in the Morris water maze task in rats.Data in the current study highlights the importance of S1PR1 signaling pathway deregulation in AD development and suggests that activation of S1PR1 may represent a potential approach for developing new therapeutics to manage memory deficit and apoptosis associated with neurodegenerative disorders such as AD.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

ABSTRACT
Sphingosine-1 phosphate (S1P) is involved in a variety of cellular processes via activation of S1P receptors (S1PRs; S1PR1 to S1PR5) that are highly expressed in the brain. It has been shown that the level of S1P is reduced in the brain of Alzheimer's disease (AD) patients. However, there is no study designed to evaluate the expression of S1PRs in AD brains. The objectives of the present work are (1) to examine the expression of S1PR1-3 in the hippocampus of beta amyloid (Aβ) 1-42 injected rats and (2) to clarify the effects of chronic S1PR1 activation on S1PR1-3 levels, spatial memory deficit and hippocampal damage in AD rats. SEW2871, the S1PR1 selective agonist, repeatedly was injected intraperitoneally during a period of two weeks. Upon Western Blot data bilateral intrahippocampal injection of Aβ1-42 decreased the expression of S1PR1 while increased S1PR2 level and did not affect that of S1PR3. We found that chronic administration of SEW2871 inhibited the reduction of S1PR1 expression and ameliorated spatial memory impairment in the Morris water maze task in rats. In addition, SEW2871 attenuated the Aβ1-42-induced hippocampal neuronal loss according to Nissl staining findings. Data in the current study highlights the importance of S1PR1 signaling pathway deregulation in AD development and suggests that activation of S1PR1 may represent a potential approach for developing new therapeutics to manage memory deficit and apoptosis associated with neurodegenerative disorders such as AD.

No MeSH data available.


Related in: MedlinePlus

Effect of SEW2871 on S1PR1-3 expression in Aβ1-42 injected rats evaluated by Western blotting method. 15 days after the stereotaxic procedure, the expression of S1PR1-3 in hippocampus was detected. Results showed decreasing of S1PR1 (A) and increasing of S1PR2 (B) in AD model rats. Treatment of AD model rats with SEW2871 resulted in elevated levels of S1PR1 (A) in hippocampus and had no effect on S1P2 (B). The expression of S1P3 did not show any change between groups (C). β-actin protein was used here as an internal control. One representative Western blot is shown; n = 6. The band density values were calculated and the values from the control were used as 1. Values are the mean ± S.E.M., **P<0.01 and ***P<0.001 vs. control group; ### P<0.001 vs. Aβ group.
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Figure 2: Effect of SEW2871 on S1PR1-3 expression in Aβ1-42 injected rats evaluated by Western blotting method. 15 days after the stereotaxic procedure, the expression of S1PR1-3 in hippocampus was detected. Results showed decreasing of S1PR1 (A) and increasing of S1PR2 (B) in AD model rats. Treatment of AD model rats with SEW2871 resulted in elevated levels of S1PR1 (A) in hippocampus and had no effect on S1P2 (B). The expression of S1P3 did not show any change between groups (C). β-actin protein was used here as an internal control. One representative Western blot is shown; n = 6. The band density values were calculated and the values from the control were used as 1. Values are the mean ± S.E.M., **P<0.01 and ***P<0.001 vs. control group; ### P<0.001 vs. Aβ group.

Mentions: In order to determine the effect of intrahippocampal injection of Aβ1-42 on S1PRs protein levels, the expressions of S1PR1-3 proteins (that are highly expressed in the brain) were evaluated by Western blotting method. Compared with control, the expression of S1PR1 was reduced prominently in rats hippocampus two weeks after Aβ1-42 (P<0.001) (Figure 2A(Fig. 2)), while the expression of S1PR2 was significantly elevated then (P<0.05) (Figure 2B(Fig. 2)) and no change was observed in S1PR3 expression (Figure 2C(Fig. 2)).


Activation of sphingosine 1-phosphate receptor-1 by SEW2871 improves cognitive function in Alzheimer's disease model rats.

Asle-Rousta M, Oryan S, Ahmadiani A, Rahnema M - EXCLI J (2013)

Effect of SEW2871 on S1PR1-3 expression in Aβ1-42 injected rats evaluated by Western blotting method. 15 days after the stereotaxic procedure, the expression of S1PR1-3 in hippocampus was detected. Results showed decreasing of S1PR1 (A) and increasing of S1PR2 (B) in AD model rats. Treatment of AD model rats with SEW2871 resulted in elevated levels of S1PR1 (A) in hippocampus and had no effect on S1P2 (B). The expression of S1P3 did not show any change between groups (C). β-actin protein was used here as an internal control. One representative Western blot is shown; n = 6. The band density values were calculated and the values from the control were used as 1. Values are the mean ± S.E.M., **P<0.01 and ***P<0.001 vs. control group; ### P<0.001 vs. Aβ group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4566907&req=5

Figure 2: Effect of SEW2871 on S1PR1-3 expression in Aβ1-42 injected rats evaluated by Western blotting method. 15 days after the stereotaxic procedure, the expression of S1PR1-3 in hippocampus was detected. Results showed decreasing of S1PR1 (A) and increasing of S1PR2 (B) in AD model rats. Treatment of AD model rats with SEW2871 resulted in elevated levels of S1PR1 (A) in hippocampus and had no effect on S1P2 (B). The expression of S1P3 did not show any change between groups (C). β-actin protein was used here as an internal control. One representative Western blot is shown; n = 6. The band density values were calculated and the values from the control were used as 1. Values are the mean ± S.E.M., **P<0.01 and ***P<0.001 vs. control group; ### P<0.001 vs. Aβ group.
Mentions: In order to determine the effect of intrahippocampal injection of Aβ1-42 on S1PRs protein levels, the expressions of S1PR1-3 proteins (that are highly expressed in the brain) were evaluated by Western blotting method. Compared with control, the expression of S1PR1 was reduced prominently in rats hippocampus two weeks after Aβ1-42 (P<0.001) (Figure 2A(Fig. 2)), while the expression of S1PR2 was significantly elevated then (P<0.05) (Figure 2B(Fig. 2)) and no change was observed in S1PR3 expression (Figure 2C(Fig. 2)).

Bottom Line: Upon Western Blot data bilateral intrahippocampal injection of Aβ1-42 decreased the expression of S1PR1 while increased S1PR2 level and did not affect that of S1PR3.We found that chronic administration of SEW2871 inhibited the reduction of S1PR1 expression and ameliorated spatial memory impairment in the Morris water maze task in rats.Data in the current study highlights the importance of S1PR1 signaling pathway deregulation in AD development and suggests that activation of S1PR1 may represent a potential approach for developing new therapeutics to manage memory deficit and apoptosis associated with neurodegenerative disorders such as AD.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

ABSTRACT
Sphingosine-1 phosphate (S1P) is involved in a variety of cellular processes via activation of S1P receptors (S1PRs; S1PR1 to S1PR5) that are highly expressed in the brain. It has been shown that the level of S1P is reduced in the brain of Alzheimer's disease (AD) patients. However, there is no study designed to evaluate the expression of S1PRs in AD brains. The objectives of the present work are (1) to examine the expression of S1PR1-3 in the hippocampus of beta amyloid (Aβ) 1-42 injected rats and (2) to clarify the effects of chronic S1PR1 activation on S1PR1-3 levels, spatial memory deficit and hippocampal damage in AD rats. SEW2871, the S1PR1 selective agonist, repeatedly was injected intraperitoneally during a period of two weeks. Upon Western Blot data bilateral intrahippocampal injection of Aβ1-42 decreased the expression of S1PR1 while increased S1PR2 level and did not affect that of S1PR3. We found that chronic administration of SEW2871 inhibited the reduction of S1PR1 expression and ameliorated spatial memory impairment in the Morris water maze task in rats. In addition, SEW2871 attenuated the Aβ1-42-induced hippocampal neuronal loss according to Nissl staining findings. Data in the current study highlights the importance of S1PR1 signaling pathway deregulation in AD development and suggests that activation of S1PR1 may represent a potential approach for developing new therapeutics to manage memory deficit and apoptosis associated with neurodegenerative disorders such as AD.

No MeSH data available.


Related in: MedlinePlus