Purple Sweet Potato Color Alleviates D-galactose-induced Brain Aging in Old Mice by Promoting Survival of Neurons via PI3K Pathway and Inhibiting Cytochrome C-mediated Apoptosis
Article first published online: 30 SEP 2009
© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
Volume 20, Issue 3, pages 598–612, May 2010
How to Cite
Lu, J., Wu, D.-m., Zheng, Y.-l., Hu, B. and Zhang, Z.-f. (2010), Purple Sweet Potato Color Alleviates D-galactose-induced Brain Aging in Old Mice by Promoting Survival of Neurons via PI3K Pathway and Inhibiting Cytochrome C-mediated Apoptosis. Brain Pathology, 20: 598–612. doi: 10.1111/j.1750-3639.2009.00339.x
- Issue published online: 12 APR 2010
- Article first published online: 30 SEP 2009
- Received 19 August 2009; accepted 27 September 2009.
- Akt pathway;
- ERK pathway;
- neuronal survival;
- oxidative stress;
- purple sweet potato color
Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, protects brain function against oxidative stress induced by D-galactose (D-gal) (Sigma-Aldrich, St. Louis, MO, USA). Our data showed that PSPC enhanced open-field activity, decreased step-through latency, and improved spatial learning and memory ability in D-gal-treated old mice by decreasing advanced glycation end-products' (AGEs) formation and the AGE receptor (RAGE) expression, and by elevating Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (Sigma-Aldrich) and catalase (CAT) expression and activity. Cleavage of caspase-3 and increased terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling (TUNEL)-positive cells in D-gal-treated old mice were inhibited by PSPC, which might be attributed to its antioxidant property. PSPC also suppressed the activation of c-Jun NH2-terminal kinase (JNK) and the release of cytochrome c from mitochondria that counteracted the onset of neuronal apoptosis in D-gal-treated old mice. Furthermore, it was demonstrated that phosphoinositide 3-kinase (PI3K) activation was required for PSPC to promote the neuronal survival accompanied with phosphorylation and activation of Akt and p44/42 mitogen-activated protein kinase (MAPK) by using PI3K inhibitor LY294002 (Cell Signaling Technology, Inc., Beverly, MA, USA), implicating a neuronal survival mechanism. The present results suggest that neuronal survival promoted by PSPC may be a potentially effective method to enhance resistance of neurons to age-related disease.