Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice
Article first published online: 6 MAR 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 83, Issue 6, pages 1028–1038, 1 May 2006
How to Cite
Denny, C. A., Kasperzyk, J. L., Gorham, K. N., Bronson, R. T. and Seyfried, T. N. (2006), Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice. J. Neurosci. Res., 83: 1028–1038. doi: 10.1002/jnr.20798
- Issue published online: 11 APR 2006
- Article first published online: 6 MAR 2006
- Manuscript Revised: 29 DEC 2005
- Manuscript Accepted: 29 DEC 2005
- Manuscript Received: 24 OCT 2005
- NIH. Grant Number: HD39722
- Boston College Research Expense Fund
- National Tay-Sachs and Allied Disease Association, Inc. (NTSAD)
Caloric restriction (CR), which improves health and increases longevity, was studied as a therapy in a hexosaminidase β knockout mouse model of Sandhoff disease (SD), an incurable neurodegenerative disease involving accumulation of brain ganglioside GM2 and asialo-GM2 (GA2). Adult mice were fed a rodent chow diet either ad libitum (AL) or restricted to reduce body weight by 15–18% (CR). Although GM2 and GA2 were elevated, no significant differences were seen between the Hexb−/− and the Hexb+/− mice for most brain phospholipids and cholesterol. Cerebrosides and sulfatides were reduced in the Hexb−/− mice. In addition, rotorod performance was significantly worse in the Hexb−/− mice than in the Hexb+/− mice. CR, which decreased circulating glucose and elevated ketone bodies, significantly improved rotorod performance and extended longevity in the Hexb−/− mice but had no significant effect on brain lipid composition or on cytoplasmic neuronal vacuoles. The expression of CD68 and F4/80 was significantly less in the CR-fed than in the AL-fed Hexb−/− mice. We suggest that the CR delays disease progression in SD and possibly in other ganglioside storage diseases through anti-inflammatory mechanisms. © 2006 Wiley-Liss, Inc.