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Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice
Author(s) -
Denny Christine A.,
Kasperzyk Julie L.,
Gorham Kristen N.,
Bronson Roderick T.,
Seyfried Thomas N.
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20798
Subject(s) - caloric theory , sandhoff disease , longevity , neuroscience , composition (language) , biology , disease , endocrinology , medicine , genetics , philosophy , linguistics
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.