Limits...
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 acute curcumin on working memory, motor function and spatial reference memory in an Aβ1-42-treated rat model of Alzheimer's disease.(A) The spontaneous alteration in the Y-maze. (B) The total arm entries in the Y-maze. (C) The total distance travelled in an open-field test. (D) Representative swim traces in the Morris water maze training trial. (E) The escape latency during the water maze training trials. (F) The time spent in the target quadrant in the probe task. n = 8 each group. * P < 0.05 and ** P < 0.01 compared with Aβ1–42 + saline group
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4482657&req=5

pone.0131525.g002: Effect of acute curcumin on working memory, motor function and spatial reference memory in an Aβ1-42-treated rat model of Alzheimer's disease.(A) The spontaneous alteration in the Y-maze. (B) The total arm entries in the Y-maze. (C) The total distance travelled in an open-field test. (D) Representative swim traces in the Morris water maze training trial. (E) The escape latency during the water maze training trials. (F) The time spent in the target quadrant in the probe task. n = 8 each group. * P < 0.05 and ** P < 0.01 compared with Aβ1–42 + saline group

Mentions: The rats were injected with a single dose of curcumin (50, 100 and 200 mg/kg, i.p.) or saline (n = 8/group) and underwent behavioral tests. Each rat only participated in one behavioral test. A one-way ANOVA was used to analyze the significance of the effect of treatment on spontaneous alternation [F (4, 35) = 4.981, P < 0.01; Fig 2A] but not total arm entries [F (4, 35) = 1.685, P = 0.1754; Fig 2B] in the Y-maze. As expected, Aβ1–42+saline rats showed a significant lower ratio of spontaneous alternation (P < 0.01) compared with sham (i.c.v. injected with saline) rats, suggesting impaired working memory in the Aβ1-42-induced rat model of Alzheimer's disease. However, Aβ1-42-treated rats injected with a single dose of curcumin of 50, 100 or 200 mg/kg did not show any improvement in spontaneous alternation (P = 0.99, 0.97 and 0.89, respectively) compared with Aβ1–42+saline rats. Next, we evaluated whether Aβ1–42 or acute curcumin could affect motor function because almost all cognitive tests rely on motor behavior. Two-way ANOVA with repeated measurements reported a significant effect of time [F (5, 210) = 22.16, P < 0.0001] but not treatment [F (4, 210) = 1.403, P = 0.234] on the total distance in OFT (Fig 2C), indicating that these rats do not exhibit locomotor deficits. We then tested spatial reference learning and memory in a Morris water maze. The representative navigation paths at the end of the water-maze training (day 10, ie. the training day 5) demonstrated that spatial learning acquisition was obviously impaired in the Aβ1-42-treated rats relative to the rats of the sham control group (Fig 2D). Further analysis revealed that the escape latencies decreased from training day 1 to day 5 in both the sham and Aβ1-42-treated groups [Ftime (4, 190) = 4.307, P < 0.01] (Fig 2E). Moreover, the i.c.v. administration of Aβ1–42 significantly attenuated the spatial learning ability of rats [Ftreatment (1, 190) = 14.70, P < 0.01]. The Aβ1-42-treated rats showed longer escape latencies than the sham rats on training days 3 and 5 (both P < 0.05). Twelve hours after the last water maze training, a single dose of curcumin was administered i.p., and the rats were subjected to the probe task to assess the spatial reference memory (Fig 2F). One-way ANOVA revealed a main effect of treatment on the time spent in the target quadrant [F (4, 35) = 5.022, P < 0.01]. However, the Aβ1–42+saline group did not differ from the Aβ1–42 combined with 50, 100 or 200 mg/kg curcumin groups (P = 0.98, 0.97 and 0.99, respectively), indicating that acute curcumin administration did not improve spatial reference memory. Moreover, sham group was significantly increased from the Aβ1–42+saline group (P < 0.01) and 25% hazard level (P < 0.0001). In addition, the visible platform version of MWM was performed to detect visual and motivational deficits. The results indicated no visual and motivational deficits in Aβ1–42 rats (S1 Fig).


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 acute curcumin on working memory, motor function and spatial reference memory in an Aβ1-42-treated rat model of Alzheimer's disease.(A) The spontaneous alteration in the Y-maze. (B) The total arm entries in the Y-maze. (C) The total distance travelled in an open-field test. (D) Representative swim traces in the Morris water maze training trial. (E) The escape latency during the water maze training trials. (F) The time spent in the target quadrant in the probe task. n = 8 each group. * P < 0.05 and ** P < 0.01 compared with Aβ1–42 + saline group
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482657&req=5

pone.0131525.g002: Effect of acute curcumin on working memory, motor function and spatial reference memory in an Aβ1-42-treated rat model of Alzheimer's disease.(A) The spontaneous alteration in the Y-maze. (B) The total arm entries in the Y-maze. (C) The total distance travelled in an open-field test. (D) Representative swim traces in the Morris water maze training trial. (E) The escape latency during the water maze training trials. (F) The time spent in the target quadrant in the probe task. n = 8 each group. * P < 0.05 and ** P < 0.01 compared with Aβ1–42 + saline group
Mentions: The rats were injected with a single dose of curcumin (50, 100 and 200 mg/kg, i.p.) or saline (n = 8/group) and underwent behavioral tests. Each rat only participated in one behavioral test. A one-way ANOVA was used to analyze the significance of the effect of treatment on spontaneous alternation [F (4, 35) = 4.981, P < 0.01; Fig 2A] but not total arm entries [F (4, 35) = 1.685, P = 0.1754; Fig 2B] in the Y-maze. As expected, Aβ1–42+saline rats showed a significant lower ratio of spontaneous alternation (P < 0.01) compared with sham (i.c.v. injected with saline) rats, suggesting impaired working memory in the Aβ1-42-induced rat model of Alzheimer's disease. However, Aβ1-42-treated rats injected with a single dose of curcumin of 50, 100 or 200 mg/kg did not show any improvement in spontaneous alternation (P = 0.99, 0.97 and 0.89, respectively) compared with Aβ1–42+saline rats. Next, we evaluated whether Aβ1–42 or acute curcumin could affect motor function because almost all cognitive tests rely on motor behavior. Two-way ANOVA with repeated measurements reported a significant effect of time [F (5, 210) = 22.16, P < 0.0001] but not treatment [F (4, 210) = 1.403, P = 0.234] on the total distance in OFT (Fig 2C), indicating that these rats do not exhibit locomotor deficits. We then tested spatial reference learning and memory in a Morris water maze. The representative navigation paths at the end of the water-maze training (day 10, ie. the training day 5) demonstrated that spatial learning acquisition was obviously impaired in the Aβ1-42-treated rats relative to the rats of the sham control group (Fig 2D). Further analysis revealed that the escape latencies decreased from training day 1 to day 5 in both the sham and Aβ1-42-treated groups [Ftime (4, 190) = 4.307, P < 0.01] (Fig 2E). Moreover, the i.c.v. administration of Aβ1–42 significantly attenuated the spatial learning ability of rats [Ftreatment (1, 190) = 14.70, P < 0.01]. The Aβ1-42-treated rats showed longer escape latencies than the sham rats on training days 3 and 5 (both P < 0.05). Twelve hours after the last water maze training, a single dose of curcumin was administered i.p., and the rats were subjected to the probe task to assess the spatial reference memory (Fig 2F). One-way ANOVA revealed a main effect of treatment on the time spent in the target quadrant [F (4, 35) = 5.022, P < 0.01]. However, the Aβ1–42+saline group did not differ from the Aβ1–42 combined with 50, 100 or 200 mg/kg curcumin groups (P = 0.98, 0.97 and 0.99, respectively), indicating that acute curcumin administration did not improve spatial reference memory. Moreover, sham group was significantly increased from the Aβ1–42+saline group (P < 0.01) and 25% hazard level (P < 0.0001). In addition, the visible platform version of MWM was performed to detect visual and motivational deficits. The results indicated no visual and motivational deficits in Aβ1–42 rats (S1 Fig).

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