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Phospholipid synthesis is decreased in neuronal tissue in a mouse model of Sandhoff disease
Author(s) -
Buccoliero Rosaria,
Bodennec Jacques,
Van EchtenDeckert Gerhild,
Sandhoff Konrad,
Futerman Anthony H.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02457.x
Subject(s) - sandhoff disease , biology , phospholipid , phosphocholine , choline , biochemistry , endocrinology , enzyme , phosphatidylcholine , membrane
Sandhoff disease is a progressive neurodegenerative disorder caused by mutations in the HEXB gene which encodes for the β‐subunit of β‐hexosaminidase A and B, resulting in ganglioside GM 2 accumulation in the brain. We now demonstrate that phospholipid metabolism is altered in both cultured neurons and in brain tissue from a mouse model of Sandhoff disease, the Hexb–/– mouse. Metabolic labelling using [methyl‐ 14 C]choline and l ‐[3‐ 3 H]serine demonstrated reduced incorporation of [methyl‐ 14 C]choline into phospholipids in brain tissue but not in liver or spleen. Phospholipid mass was also reduced in brain. The activities of CTP : phosphocholine cytidylyltransferase (CCT) and phosphatidylserine synthase were also reduced in brain tissue from Hexb–/– mice, probably because of post‐translational modification as no changes were observed in levels of enzyme expression. The relevance of these findings to Sandhoff disease in human patients is strengthened by observations made over 30 years ago on autopsy tissue of Tay Sachs and Sandhoff disease patients, in which reduced phospholipid levels were observed. We suggest that changes in phospholipid metabolism are not simply because of loss of neuronal tissue as a result of degeneration but rather may cause degeneration, and we discuss the possible effects that changes in phospholipid metabolism could play in the neuropathophysiology of Sandhoff disease.