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Curcumin Improves Amyloid β-Peptide (1-42) Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway.

Zhang L, Fang Y, Xu Y, Lian Y, Xie N, Wu T, Zhang H, Sun L, Zhang R, Wang Z - PLoS ONE (2015)

Bottom Line: Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects.In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus.Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor.

View Article: PubMed Central - PubMed

Affiliation: Key-Disciplines Laboratory Clinical-Medicine of Henan, Zhengzhou, Henan, PR China; Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China.

ABSTRACT
Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer's disease (AD). However, the molecular mechanisms underlying curcumin's effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42), representing a rodent model of Alzheimer's disease (AD). The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day) but not acute (once a day) curcumin treatments (50, 100, and 200 mg/kg) improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

No MeSH data available.


Related in: MedlinePlus

Effect of chronic curcumin treatment on BDNF expression and GSK3β, MAPK phosphorylation in the hippocampus.Upper-left: representative western blots of BDNF and GSK3β in each group. GAPDH was used as the internal loading control. Upper-right: relative expression of BDNF expression phosphorylated GSK3β. Lower-left: representative western blots of ERK, JNK and p38 phosphorylation in each group. Lower-right: relative expression of phosphorylated ERK, JNK and p38. Protein phosphorylation was expressed as phosphorylated form vs. total protein. * P < 0.05 and ** P < 0.01 compared with Aβ1–42 + saline.
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pone.0131525.g004: Effect of chronic curcumin treatment on BDNF expression and GSK3β, MAPK phosphorylation in the hippocampus.Upper-left: representative western blots of BDNF and GSK3β in each group. GAPDH was used as the internal loading control. Upper-right: relative expression of BDNF expression phosphorylated GSK3β. Lower-left: representative western blots of ERK, JNK and p38 phosphorylation in each group. Lower-right: relative expression of phosphorylated ERK, JNK and p38. Protein phosphorylation was expressed as phosphorylated form vs. total protein. * P < 0.05 and ** P < 0.01 compared with Aβ1–42 + saline.

Mentions: To observe the effects of chronic curcumin on BDNF, GSK3β and MAPK activation in the Aβ1-42-treated rat model of Alzheimer's disease, a new cohort of animals was injected with curcumin (i.p., once per day) for 7 consecutive days and killed 30 min after the last injection. The expression of levels BDNF, total GSK3β, ERK, JNK and p38, as well as their phosphorylated (activated) forms in the hippocampus were analyzed (Fig 4). Treatment significantly affected the BDNF expression in the hippocampus [F (4, 35) = 4.525, P = 0.0047]. The expression of BDNF was significantly promoted in the Aβ1–42+Cur (100 and 200 mg/kg, P < 0.01 and 0.05) and the sham group (P < 0.05) as compared with the Aβ1–42+saline group. However, the repeated administration of 50 mg/kg curcumin did not affect the BDNF levels (P = 0.987). The phosphorylation of GSK3β [F (4, 35) = 5.328, P = 0.0019] was significantly decreased by repeated administration of 100 and 200 mg/kg curcumin compared with the Aβ1–42+saline groups. Furthermore, there was no difference in phospho-GSK3β between the Aβ1–42+saline and the Aβ1–42+Cur (50 mg/kg) group (P = 0.8478). The level of total GSK3β did not differ among groups [F (4, 35) = 0.5644, P = 0.7509]. A one-way ANOVA revealed a significant effect of treatments on the phosphorylation of ERK [F (4, 35) = 11.37, P < 0.0001] but not on JNK [F (4, 35) = 0.2659, P = 0.8978] or p38 [F (4, 35) = 0.3674, P = 0.8302]. A post hoc analysis showed that the levels of phospho-ERK in the Aβ1–42+Cur (100 and 200 mg/kg, P < 0.05 and 0.0001) and the sham group (P < 0.05) were significantly higher than in the Aβ1–42+saline group. Phospho-ERK in the Aβ1–42+Cur (50 mg/kg) was similar to the sham group (P = 0.9691).


Curcumin Improves Amyloid β-Peptide (1-42) Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway.

Zhang L, Fang Y, Xu Y, Lian Y, Xie N, Wu T, Zhang H, Sun L, Zhang R, Wang Z - PLoS ONE (2015)

Effect of chronic curcumin treatment on BDNF expression and GSK3β, MAPK phosphorylation in the hippocampus.Upper-left: representative western blots of BDNF and GSK3β in each group. GAPDH was used as the internal loading control. Upper-right: relative expression of BDNF expression phosphorylated GSK3β. Lower-left: representative western blots of ERK, JNK and p38 phosphorylation in each group. Lower-right: relative expression of phosphorylated ERK, JNK and p38. Protein phosphorylation was expressed as phosphorylated form vs. total protein. * P < 0.05 and ** P < 0.01 compared with Aβ1–42 + saline.
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Related In: Results  -  Collection

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pone.0131525.g004: Effect of chronic curcumin treatment on BDNF expression and GSK3β, MAPK phosphorylation in the hippocampus.Upper-left: representative western blots of BDNF and GSK3β in each group. GAPDH was used as the internal loading control. Upper-right: relative expression of BDNF expression phosphorylated GSK3β. Lower-left: representative western blots of ERK, JNK and p38 phosphorylation in each group. Lower-right: relative expression of phosphorylated ERK, JNK and p38. Protein phosphorylation was expressed as phosphorylated form vs. total protein. * P < 0.05 and ** P < 0.01 compared with Aβ1–42 + saline.
Mentions: To observe the effects of chronic curcumin on BDNF, GSK3β and MAPK activation in the Aβ1-42-treated rat model of Alzheimer's disease, a new cohort of animals was injected with curcumin (i.p., once per day) for 7 consecutive days and killed 30 min after the last injection. The expression of levels BDNF, total GSK3β, ERK, JNK and p38, as well as their phosphorylated (activated) forms in the hippocampus were analyzed (Fig 4). Treatment significantly affected the BDNF expression in the hippocampus [F (4, 35) = 4.525, P = 0.0047]. The expression of BDNF was significantly promoted in the Aβ1–42+Cur (100 and 200 mg/kg, P < 0.01 and 0.05) and the sham group (P < 0.05) as compared with the Aβ1–42+saline group. However, the repeated administration of 50 mg/kg curcumin did not affect the BDNF levels (P = 0.987). The phosphorylation of GSK3β [F (4, 35) = 5.328, P = 0.0019] was significantly decreased by repeated administration of 100 and 200 mg/kg curcumin compared with the Aβ1–42+saline groups. Furthermore, there was no difference in phospho-GSK3β between the Aβ1–42+saline and the Aβ1–42+Cur (50 mg/kg) group (P = 0.8478). The level of total GSK3β did not differ among groups [F (4, 35) = 0.5644, P = 0.7509]. A one-way ANOVA revealed a significant effect of treatments on the phosphorylation of ERK [F (4, 35) = 11.37, P < 0.0001] but not on JNK [F (4, 35) = 0.2659, P = 0.8978] or p38 [F (4, 35) = 0.3674, P = 0.8302]. A post hoc analysis showed that the levels of phospho-ERK in the Aβ1–42+Cur (100 and 200 mg/kg, P < 0.05 and 0.0001) and the sham group (P < 0.05) were significantly higher than in the Aβ1–42+saline group. Phospho-ERK in the Aβ1–42+Cur (50 mg/kg) was similar to the sham group (P = 0.9691).

Bottom Line: Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects.In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus.Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor.

View Article: PubMed Central - PubMed

Affiliation: Key-Disciplines Laboratory Clinical-Medicine of Henan, Zhengzhou, Henan, PR China; Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China.

ABSTRACT
Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer's disease (AD). However, the molecular mechanisms underlying curcumin's effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42), representing a rodent model of Alzheimer's disease (AD). The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day) but not acute (once a day) curcumin treatments (50, 100, and 200 mg/kg) improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

No MeSH data available.


Related in: MedlinePlus