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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 working memory, motor function and spatial reference memory in Alzheimer's disease rats.(A) The spontaneous alteration in the Y-maze. (B) The total arm entries in Y-maze. (C) The total distance travelled in open-field test. (D) The escape latency during the water maze training trials. (E) Representative swim traces in the probe task. For panel D, *P < 0.05 and ***P < 0.0001 comparison between Aβ1–42 + saline and sham; # P < 0.05 and ###P < 0.0001 comparison between curcumin (200 mg/kg) and Aβ1–42 + saline. (F) The time spent in the target quadrant in the probe task. n = 8 each group. **P < 0.01 and ***P < 0.0001 compared with Aβ1–42 + saline.
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pone.0131525.g003: Effect of chronic curcumin treatment on working memory, motor function and spatial reference memory in Alzheimer's disease rats.(A) The spontaneous alteration in the Y-maze. (B) The total arm entries in Y-maze. (C) The total distance travelled in open-field test. (D) The escape latency during the water maze training trials. (E) Representative swim traces in the probe task. For panel D, *P < 0.05 and ***P < 0.0001 comparison between Aβ1–42 + saline and sham; # P < 0.05 and ###P < 0.0001 comparison between curcumin (200 mg/kg) and Aβ1–42 + saline. (F) The time spent in the target quadrant in the probe task. n = 8 each group. **P < 0.01 and ***P < 0.0001 compared with Aβ1–42 + saline.

Mentions: Rats were treated with curcumin (50, 100 and 200 mg/kg, i.p., once per day) or saline (n = 8/group) for 5 consecutive days. Each rat only participated in one of the behavioral tests, including the Y-maze, OFT or Morris water maze. Chronic treatments significantly affected the spontaneous alternation [F (4, 35) = 6.046, P < 0.01; Fig 3A] but not total arm entries [F (4, 35) = 0.5965, P = 0.6675; Fig 3B]. The spontaneous alternation in the Aβ1–42+Cur (50 mg/kg) and Aβ1–42+Cur (100 mg/kg) groups were not differ from the Aβ1–42+saline group (P = 0.98 and 0.95, respectively). However, there was a significant increase of the spontaneous alternation in the 200 mg/kg curcumin-treated rats (P < 0.05), indicating an amelioration in working memory. A significant effect of time [F (5, 210) = 18.08, P < 0.0001] but not treatment [F (4, 210) = 1.125, P = 0.3459] on the total distance of OFT was observed, suggesting no locomotor deficits in these rats (Fig 3C). The escape latencies significantly decreased after the chronic administration of 100 and 200 mg/kg curcumin [Ftreatment (4, 295) = 4.813, P < 0.01; Ftime (4, 295) = 15.97, P < 0.0001; Fig 3D]. The representative navigation paths in the probe trials are shown in Fig 3E. In the probe trials, chronic curcumin treatment significantly affected the time spend in the target quadrant [F (4, 35) = 4.342, P < 0.01; Fig 3F]. The time spent in the target quadrant in the sham and Aβ1–42+Cur (100 and 200 mg/kg)-treated rats were significantly higher than the Aβ1–42+saline rats (all P < 0.01), indicating that the spatial memory markedly improved in the Alzheimer's disease rats. Moreover, Aβ1–42+Cur (100 and 200 mg/kg) and the sham group were significantly higher vs the 25% hazard level (P < 0.0001 of all groups). To rule out the possible effect of curcumin per se on the spatial memory, we conducted the chronic curcumin administration without Aβ injection (ie. sham+Cur group) to address this concern. No significant effect of curcumin (50, 100 and 200 mg/kg) was found on the spatial learn memory (S2 Fig), indicating that the chronic curcumin administration per se do not affect spatial memory.


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 working memory, motor function and spatial reference memory in Alzheimer's disease rats.(A) The spontaneous alteration in the Y-maze. (B) The total arm entries in Y-maze. (C) The total distance travelled in open-field test. (D) The escape latency during the water maze training trials. (E) Representative swim traces in the probe task. For panel D, *P < 0.05 and ***P < 0.0001 comparison between Aβ1–42 + saline and sham; # P < 0.05 and ###P < 0.0001 comparison between curcumin (200 mg/kg) and Aβ1–42 + saline. (F) The time spent in the target quadrant in the probe task. n = 8 each group. **P < 0.01 and ***P < 0.0001 compared with Aβ1–42 + saline.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131525.g003: Effect of chronic curcumin treatment on working memory, motor function and spatial reference memory in Alzheimer's disease rats.(A) The spontaneous alteration in the Y-maze. (B) The total arm entries in Y-maze. (C) The total distance travelled in open-field test. (D) The escape latency during the water maze training trials. (E) Representative swim traces in the probe task. For panel D, *P < 0.05 and ***P < 0.0001 comparison between Aβ1–42 + saline and sham; # P < 0.05 and ###P < 0.0001 comparison between curcumin (200 mg/kg) and Aβ1–42 + saline. (F) The time spent in the target quadrant in the probe task. n = 8 each group. **P < 0.01 and ***P < 0.0001 compared with Aβ1–42 + saline.
Mentions: Rats were treated with curcumin (50, 100 and 200 mg/kg, i.p., once per day) or saline (n = 8/group) for 5 consecutive days. Each rat only participated in one of the behavioral tests, including the Y-maze, OFT or Morris water maze. Chronic treatments significantly affected the spontaneous alternation [F (4, 35) = 6.046, P < 0.01; Fig 3A] but not total arm entries [F (4, 35) = 0.5965, P = 0.6675; Fig 3B]. The spontaneous alternation in the Aβ1–42+Cur (50 mg/kg) and Aβ1–42+Cur (100 mg/kg) groups were not differ from the Aβ1–42+saline group (P = 0.98 and 0.95, respectively). However, there was a significant increase of the spontaneous alternation in the 200 mg/kg curcumin-treated rats (P < 0.05), indicating an amelioration in working memory. A significant effect of time [F (5, 210) = 18.08, P < 0.0001] but not treatment [F (4, 210) = 1.125, P = 0.3459] on the total distance of OFT was observed, suggesting no locomotor deficits in these rats (Fig 3C). The escape latencies significantly decreased after the chronic administration of 100 and 200 mg/kg curcumin [Ftreatment (4, 295) = 4.813, P < 0.01; Ftime (4, 295) = 15.97, P < 0.0001; Fig 3D]. The representative navigation paths in the probe trials are shown in Fig 3E. In the probe trials, chronic curcumin treatment significantly affected the time spend in the target quadrant [F (4, 35) = 4.342, P < 0.01; Fig 3F]. The time spent in the target quadrant in the sham and Aβ1–42+Cur (100 and 200 mg/kg)-treated rats were significantly higher than the Aβ1–42+saline rats (all P < 0.01), indicating that the spatial memory markedly improved in the Alzheimer's disease rats. Moreover, Aβ1–42+Cur (100 and 200 mg/kg) and the sham group were significantly higher vs the 25% hazard level (P < 0.0001 of all groups). To rule out the possible effect of curcumin per se on the spatial memory, we conducted the chronic curcumin administration without Aβ injection (ie. sham+Cur group) to address this concern. No significant effect of curcumin (50, 100 and 200 mg/kg) was found on the spatial learn memory (S2 Fig), indicating that the chronic curcumin administration per se do not affect spatial memory.

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