Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice.
Caloric restriction (CR), which improves health and increases longevity, was studied as a therapy in a hexosaminidase beta 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.
Denny
Christine A
CA
Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Kasperzyk
Julie L
JL
Gorham
Kristen N
KN
Bronson
Roderick T
RT
Seyfried
Thomas N
TN
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000367:Age Factors; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D001786:Blood Glucose; D015153:Blotting, Western / Q000379:methods; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D031204:Caloric Restriction; D002452:Cell Count / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D054819:Hexosaminidase B; D007150:Immunohistochemistry / Q000379:methods; D008055:Lipids; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D045442:Rotarod Performance Test / Q000379:methods; D012497:Sandhoff Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D001619:beta-N-Acetylhexosaminidases / Q000172:deficiency; D000097382:CD68 Molecule
D020155:3-Hydroxybutyric Acid; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D001786:Blood Glucose; D054819:Hexosaminidase B; D008055:Lipids; D012333:RNA, Messenger; D001619:beta-N-Acetylhexosaminidases; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C036763:monocyte-macrophage differentiation antigen