Research Interests
Our neuroscience research is focused on changes in the structure and
function of glycosylations from embryonic development to aging and in
neurodegenerative disease.
We began this study focusing on neutral glycosylations expressed on the
surface of sensory afferent neurons. For technical reasons, so far, it
has not been possible to study the biological functions of such glycosylation
in vertebrate organisms. Therefore, we used the leech embryo whose intact
nervous system can be experimentally manipulated with Fab fragments, enzymes
and neoglycoproteins. We found that sensory afferents used a constitutive
mannosidic epitope to sprout filopodia and proliferate synaptic vesicles
during their initial exploration of central target regions.
Subsequently, galactosidic epitopes emerge that divide these sensory
afferents into subsets correlating with their different sensory modalities.
These developmentally regulated galactosidic epitopes now oppose the function
of the constitutive mannosidic epitope by inhibiting filopodial sprouting
and synaptic vesicle hypertrophy. As a result, afferent subset consolidate
into different lamina and form en passant synapses. The transformation
of sensory afferent growth, progressing from mannose- to galactose-specific
recognition, is consistent with a change from cell-matrix to cell-cell
contact. While the constitutive mannosidic glycosylation promotes dynamic
growth, developmentally regulated galactosidic glycosylations promote
tissue stability. The persistence of both types of neutral glycans beyond
embryonic age allows their function in synaptic plasticity during habituation
and learning.
Currently, we are studying neutral polysaccharides in the human brain.
In our initial studies, we found that Alzheimer’s disease brains
accumulate amylose, the unbranched alpha- (1,4) linked glucose polymer
that is resistant to degradation by glycolytic enzymes. Five percent of
the neutral polysaccharides (50 mg [0.3mmol]/g of wet weight brain tissue)
purified from Alzheimer frontal cerebrum consisted of amylose with molecular
weights exceeding 600,000Da. There is no evidence for 1,6 branching indicating
that the polymer is not a form of high molecular weight glycogen. A synthesis
of amylose in AD brains at the expense of glycogen would compromise glucose
metabolism and enhance neural degeneration. Now, we are studying a novel
type of polysaccharides, termed chitinaceous polymers. Chitinaceous polymers
change in molecular size and composition with age and disease.
Please feel free to contact me if you have any questions about my research.
Selected Publications
Search all publications in the NCBI Journal Database
Huang, L. Hollingsworth, R. I., Castellani, R., and Zipser, B. (2004). Accumulation of high molecular weight amylose in Alzheimer's disease brains. Glycobiology 14:409-416.
Zipser B, Bradford JJ, Hollingsworth RI (1998) Structural analysis of leech galactocerebrosides using one and two dimensional NMR spectroscopy, GC-MS, ESI and FAB mass spectrometry. Carbohydrate Research 308: 47-55.
Song, J and Zipser, B (1995) Targeting of axonal subsets mediated by their sequentially expressed carbohydrate markers. Neuron 14: 537-547.
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Birgit
Zipser