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 intra-hippocampal injections of BDNF protein or lentiviral-shBDNF on spatial learning function in the rat model of Alzheimer's disease.(A) Schematic representation showing the approximate location of microinjections into the VLO. Only rats with injection cannula tips located bilaterally in this site were included. (B) Swim speed in each training trial. (C) The escape latency during the water maze training trials. (D) The time spent in the target quadrant and (E) the number of times crossing the platform in the probe task. n = 8/group. For panel C, ***P < 0.0001, Aβ1–42 + saline vs sham; # P < 0.05, ### P < 0.0001, Aβ1–42 + BDNF vs. Aβ1–42 + saline group; ^ P < 0.05, Aβ1–42 + Cur vs. Aβ1–42 + saline group. For other panels, * P < 0.05, ** P < 0.01, *** P < 0.0001 compared with Aβ1–42 + saline.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131525.g005: Effect of intra-hippocampal injections of BDNF protein or lentiviral-shBDNF on spatial learning function in the rat model of Alzheimer's disease.(A) Schematic representation showing the approximate location of microinjections into the VLO. Only rats with injection cannula tips located bilaterally in this site were included. (B) Swim speed in each training trial. (C) The escape latency during the water maze training trials. (D) The time spent in the target quadrant and (E) the number of times crossing the platform in the probe task. n = 8/group. For panel C, ***P < 0.0001, Aβ1–42 + saline vs sham; # P < 0.05, ### P < 0.0001, Aβ1–42 + BDNF vs. Aβ1–42 + saline group; ^ P < 0.05, Aβ1–42 + Cur vs. Aβ1–42 + saline group. For other panels, * P < 0.05, ** P < 0.01, *** P < 0.0001 compared with Aβ1–42 + saline.

Mentions: Chronic curcumin (100 mg/kg, i.p.) or saline (sham rats) were administered as previously described. BDNF (1.0 μg/side) or lentiviral-shBDNF was injected bilaterally into the hippocampus 30 min after curcumin injection. At the end of the behavioral test, the rats were killed, and their brains were removed. The cannula tracks and injection sites in the hippocampus were verified, and an example is shown in Fig 5A. The cannula lesion and injection sites were well localized to the dorsal hippocampus. Thirty-eight animals in total were included in the final analyses (sham group, n = 7; Aβ1–42+saline group, n = 8; Aβ1–42+Cur group, n = 8; Aβ1–42+BDNF group, n = 7; Aβ1–42+Cur+shBDNF group, n = 8). Two rats were discarded due to misplaced injection sites. No changes in swimming speed were observed in these rats during the entire water maze training period [Ftreatment (4, 167) = 0.1839, P = 0.9465; Ftime (4, 167) = 0.1581, P = 0.9591] (Fig 5B), indicating no locomotor deficits in these rats. Two-way ANOVA revealed a significant effect of drug treatments [Ftreatment (4, 283) = 4.246, P = 0.0023] as well as time [Ftime (4, 283) = 20.64, P < 0.0001] on the escape latency (Fig 5C). In the probe trial, the amount of time in the quadrant was significantly higher in the Aβ1–42+Cur, Aβ1–42+BDNF and the sham group than in the Aβ1–42+saline group (P < 0.01, 0.0001 and 0.0001, respectively) (Fig 5D). Moreover, Aβ1–42+Cur, Aβ1–42+BDNF and the sham group were significantly higher vs the 25% hazard level (P < 0.0001 of all groups). No obvious difference in the platform crossing was observed between the Aβ1–42+saline, Aβ1–42+Cur, Aβ1–42+BDNF and Aβ1–42+Cur+shBDNF groups (Fig 5E). Moreover, the amount of time in the quadrant and number of times the platform crossed did not significantly differ between the Aβ1–42+salineand Aβ1–42+Cur+shBDNF rats, indicating that intra-hippocampus shBDNF administration completely blocked chronic curcumin-induced cognitive improvement.


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 intra-hippocampal injections of BDNF protein or lentiviral-shBDNF on spatial learning function in the rat model of Alzheimer's disease.(A) Schematic representation showing the approximate location of microinjections into the VLO. Only rats with injection cannula tips located bilaterally in this site were included. (B) Swim speed in each training trial. (C) The escape latency during the water maze training trials. (D) The time spent in the target quadrant and (E) the number of times crossing the platform in the probe task. n = 8/group. For panel C, ***P < 0.0001, Aβ1–42 + saline vs sham; # P < 0.05, ### P < 0.0001, Aβ1–42 + BDNF vs. Aβ1–42 + saline group; ^ P < 0.05, Aβ1–42 + Cur vs. Aβ1–42 + saline group. For other panels, * P < 0.05, ** P < 0.01, *** P < 0.0001 compared with Aβ1–42 + saline.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131525.g005: Effect of intra-hippocampal injections of BDNF protein or lentiviral-shBDNF on spatial learning function in the rat model of Alzheimer's disease.(A) Schematic representation showing the approximate location of microinjections into the VLO. Only rats with injection cannula tips located bilaterally in this site were included. (B) Swim speed in each training trial. (C) The escape latency during the water maze training trials. (D) The time spent in the target quadrant and (E) the number of times crossing the platform in the probe task. n = 8/group. For panel C, ***P < 0.0001, Aβ1–42 + saline vs sham; # P < 0.05, ### P < 0.0001, Aβ1–42 + BDNF vs. Aβ1–42 + saline group; ^ P < 0.05, Aβ1–42 + Cur vs. Aβ1–42 + saline group. For other panels, * P < 0.05, ** P < 0.01, *** P < 0.0001 compared with Aβ1–42 + saline.
Mentions: Chronic curcumin (100 mg/kg, i.p.) or saline (sham rats) were administered as previously described. BDNF (1.0 μg/side) or lentiviral-shBDNF was injected bilaterally into the hippocampus 30 min after curcumin injection. At the end of the behavioral test, the rats were killed, and their brains were removed. The cannula tracks and injection sites in the hippocampus were verified, and an example is shown in Fig 5A. The cannula lesion and injection sites were well localized to the dorsal hippocampus. Thirty-eight animals in total were included in the final analyses (sham group, n = 7; Aβ1–42+saline group, n = 8; Aβ1–42+Cur group, n = 8; Aβ1–42+BDNF group, n = 7; Aβ1–42+Cur+shBDNF group, n = 8). Two rats were discarded due to misplaced injection sites. No changes in swimming speed were observed in these rats during the entire water maze training period [Ftreatment (4, 167) = 0.1839, P = 0.9465; Ftime (4, 167) = 0.1581, P = 0.9591] (Fig 5B), indicating no locomotor deficits in these rats. Two-way ANOVA revealed a significant effect of drug treatments [Ftreatment (4, 283) = 4.246, P = 0.0023] as well as time [Ftime (4, 283) = 20.64, P < 0.0001] on the escape latency (Fig 5C). In the probe trial, the amount of time in the quadrant was significantly higher in the Aβ1–42+Cur, Aβ1–42+BDNF and the sham group than in the Aβ1–42+saline group (P < 0.01, 0.0001 and 0.0001, respectively) (Fig 5D). Moreover, Aβ1–42+Cur, Aβ1–42+BDNF and the sham group were significantly higher vs the 25% hazard level (P < 0.0001 of all groups). No obvious difference in the platform crossing was observed between the Aβ1–42+saline, Aβ1–42+Cur, Aβ1–42+BDNF and Aβ1–42+Cur+shBDNF groups (Fig 5E). Moreover, the amount of time in the quadrant and number of times the platform crossed did not significantly differ between the Aβ1–42+salineand Aβ1–42+Cur+shBDNF rats, indicating that intra-hippocampus shBDNF administration completely blocked chronic curcumin-induced cognitive improvement.

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