Xu Y, Ku B, Cui L, Li X, Barish PA, Foster TC et al. Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1a mrna and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res 1162: 9-18

Department of Biomedical Engineering, University of Florida, Gainesville, FL, 32611, USA.
Brain Research (Impact Factor: 2.84). 09/2007; 1162(1):9-18. DOI: 10.1016/j.brainres.2007.05.071
Source: PubMed


Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicine, which has been used to effectively manage stress and depression-related disorders in China. As the active component of curcuma longa, curcumin possesses many therapeutic properties; we have previously described its antidepressant activity in our earlier studies using the chronic unpredictable stress model of depression in rats. Recent studies show that stress-induced damage to hippocampal neurons may contribute to the phathophysiology of depression. The aim of this study was to investigate the effects of curcumin on hippocampal neurogenesis in chronically stressed rats. We used an unpredictable chronic stress paradigm (20 days) to determine whether chronic curcumin treatment with the effective doses for behavioral responses (5, 10 and 20 mg/kg, p.o.), could alleviate or reverse the effects of stress on adult hippocampal neurogenesis. Our results suggested that curcumin administration (10 and 20 mg/kg, p.o.) increased hippocampal neurogenesis in chronically stressed rats, similar to classic antidepressant imipramine treatment (10 mg/kg, i.p.). Our results further demonstrated that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. In addition, curcumin significantly prevented the stress-induced decrease in 5-HT(1A) mRNA and BDNF protein levels in the hippocampal subfields, two molecules involved in hippocampal neurogenesis. These results raise the possibility that increased cell proliferation and neuronal populations may be a mechanism by which curcumin treatment overcomes the stress-induced behavioral abnormalities and hippocampal neuronal damage. Moreover, curcumin treatment, via up-regulation of 5-HT(1A) receptors and BDNF, may reverse or protect hippocampal neurons from further damage in response to chronic stress, which may underlie the therapeutic actions of curcumin.

Download full-text


Available from: William O Ogle,
  • Source
    • "The dose of curcumin administration was selected through the previous literature [10] [11] and modified from preliminary experiments. Two hours after reperfusion, blood and liver tissue samples were obtained for further analysis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: In this study, we investigated the protective effect and mechanism of curcumin on a rat model of intestinal ischemia/reperfusion (I/R), which induces an acute liver lesion. Methods: Curcumin was injected into rats in the curcumin groups through left femoral vein. The same volume of vehicle (0.9% normal saline) was injected into sham and I/R groups. Blood and liver tissue were gathered for serological and histopathological determination. Results: Intestinal I/R led to severe liver injury manifested as a significant increase in serum AST and ALT levels; all of those were reduced by treatment with curcumin. Simultaneously, the activity of SOD in liver decreased after intestinal I/R, which was increased by curcumin treatment. On the other hand, curcumin reduced MPO activity of liver tissue, as well as serum IL-6 and TNF-α levels observably. This is in parallel with the decreased level of liver intercellular cell adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) expression. Conclusion: Our findings suggest that curcumin treatment attenuates liver lesion induced by intestinal I/R, attributable to the antioxidative and anti-inflammatory effect via inhibition of the NF-κB pathway.
    Oxidative medicine and cellular longevity 08/2014; 2014:191624. DOI:10.1155/2014/191624 · 3.36 Impact Factor
  • Source
    • "As an important element in the development of depression, anxiety is often characterized by excessive fear and reluctance to explore a novel environment. These behavioral deficits can be reversed by antidepressant treatments [30]. Previous studies suggested that inhibitors of PDEs, such as PDE4 and PDE5, ameliorate stress-related depression-and anxiety-like behaviors through regulating the cAMP or cGMP signaling [31] [32]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Stress occurs in everyday life, but the relationship between stress and the onset or development of depression/anxiety remains unknown. Increasing evidence suggests that the impairment of antioxidant defense and the neuronal cell death are important in the process of emotional disorders. Chronic stress impairs the homeostasis of antioxidants/oxidation, which results in the aberrant stimulation of the cell cycle proteins where cGMP-PKG signaling is thought to have an inhibitory role. Phosphodiesterase 2 (PDE2) is linked to cGMP-PKG signaling and highly expressed in the limbic brain regions including hippocampus and amygdala, which may play important roles in the treatment of depression and anxiety. To address the possible effects of PDE2 inhibitors on depression-/anxiety-like behaviors and the underlying mechanisms, Bay 60-7550 (0.75, 1.5 and 3mg/kg, i.p.) was administered 30min before chronic stress. The results suggested that Bay 60-7550 not only restored the behavioral changes but also regulated Cu/Zn superoxide dismutase (SOD) levels differentially in hippocampus and amygdala, which were increased in the hippocampus while decreased in the amygdala. It was also significant that Bay 60-7550 regulated the abnormalities of pro- and anti-apoptotic components, such as Bax, Caspase 3 and Bcl-2, and the indicator of PKG signaling characterized by pVASP(ser239), in these two brain regions. The results suggested that Bay 60-7550 is able to alleviate oxidative stress and mediate part of the apoptotic machinery in neuronal cells possibly through SOD-cGMP/PKG-anti-apoptosis signaling and that inhibition of PDE2 may represent a novel therapeutic target for psychiatric disorders, such as depression and anxiety.
    Behavioural brain research 03/2014; 268. DOI:10.1016/j.bbr.2014.03.042 · 3.03 Impact Factor
    • "This enhancement of VEGF level appeared to be responsible for the neurogenesis in the MCAO rats.[29] Fuzi, kam-ondam tang, and curcumin have been reported to be able to increase the mRNA and protein levels of BDNF in the mouse hippocampus, respectively.[103031] Furthermore, the beneficial effects of Fuzi on hippocampal neurogenesis were neutralized by using TrkB receptor blocker, K252a.[31] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adult neurogenesis is an important therapeutic target in treating neurological disorders. Adult neurogenesis takes place in two regions of the brain: Subventricular zone and dentate gyrus in the hippocampus. The progressive understanding on hippocampal neurogenesis in aging and mood disorders increases the demand to explore powerful and subtle interventions on hippocampal neurogenesis. Traditional Chinese herbal medicine provides an abundant pharmaceutical platform for modulating hippocampal neurogenesis. Recent progress in exploring the effects of Chinese herbal medicine and the related mechanisms opens a new direction for regeneration therapy. The current review gives a thorough summary of the research progress made in traditional Chinese herbal formulas, and the effective compounds in Chinese herbs which are beneficial on hippocampal neurogenesis and the possible mechanisms involved.
    Journal of Traditional and Complementary Medicine 03/2014; 4(2):77-81. DOI:10.4103/2225-4110.130372
Show more