Effects of Curcumin (Curcuma longa) on Learning and Spatial Memory as Well as Cell Proliferation and Neuroblast Differentiation in Adult and Aged Mice by Upregulating Brain-Derived Neurotrophic Factor and CREB Signaling

Abstract

Aging is a progressive process, and it may lead to the initiation of neurological diseases. In this study, we investigated the effects of wild Indian Curcuma longa using a Morris water maze paradigm on learning and spatial memory in adult and D-galactose-induced aged mice. In addition, the effects on cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin (DCX) respectively. The aging model in mice was induced through the subcutaneous administration of D-galactose (100 mg/kg) for 10 weeks. C. longa (300 mg/kg) or its vehicle (physiological saline) was administered orally to adult and D-galactose-treated mice for the last three weeks before sacrifice. The administration of C. longa significantly shortened the escape latency in both adult and D-galactose-induced aged mice and significantly ameliorated D-galactose-induced reduction of cell proliferation and neuroblast differentiation in the subgranular zone of hippocampal dentate gyrus. In addition, the administration of C. longa significantly increased the levels of phosphorylated CREB and brain-derived neurotrophic factor in the subgranular zone of dentate gyrus. These results indicate that C. longa mitigates D-galactose-induced cognitive impairment, associated with decreased cell proliferation and neuroblast differentiation, by activating CREB signaling in the hippocampal dentate gyrus.

Neurotrophic effects of turmeric on the memory of the mouse using the Morris water maze test

“…Moreover, curcumin treatment significantly improved colchicine-induced cognitive impairment in mice by decreasing lipid peroxidation. [9] This statement strengthened the claim of Ataie et al, [19] who studied the effects of curcumin in the lipid peroxidation of the brain of which there is increased latency in passive avoidance tests.…”

“…Moreover, curcumin treatment significantly improved colchicine-induced cognitive impairment in mice by decreasing lipid peroxidation. [9] This statement strengthened the claim of Ataie et al, [19] who studied the effects of curcumin in the lipid peroxidation of the brain of which there is increased latency in passive avoidance tests.The data above agrees with the study of Ataie et al, [19] where the turmeric treatments at low, middle, and high doses (5 mg/kg, 15 mg/kg, and 45 mg/kg, respectively) have inhibited lipid peroxidation significantly. He further stated that curcumin at the dose of 45 mg/kg has inhibited apoptosis in the hippocampus most efficiently; thus, curcumin has dose-related antioxidant effects on the whole brain tissue.…”

“…[8,10] Accordingly, Nam et al [9] reported that the protective effect of curcumin is mediated by the prevention of oxidative stress leading to apoptosis. Curcumin as an antioxidant primarily protects biomembranes against peroxidative damage, a free-radical-mediated chain reaction, damaging cell membranes.…”

“…[4] Curcumin's preventative and protective roles on learning and memory is related to apoptotic effect, as it impairs the consolidation of memory and reverses cognitive alterations, by inhibiting programmed cell death. [8,10] Accordingly, Nam et al [9] reported that the protective effect of curcumin is mediated by the prevention of oxidative stress leading to apoptosis. Curcumin as an antioxidant primarily protects biomembranes against peroxidative damage, a free-radical-mediated chain reaction, damaging cell membranes.…”

“…The protective effect on memory deficit is mediated by prevention of oxidative stress. [9] Curcumin protects the brain mitochondria against various oxidative stress, such as peroxynitrite, a product of the reaction of nitric oxide with superoxide. Curcumin has also been shown to reduce the levels of amyloid and oxidized proteins and prevents memory deficits, and is thus beneficial to patients with Alzheimer's disease.…”