NDLI: Defects in the Medial Entorhinal Cortex and Dentate Gyrus in the Mouse Model of Sanfilippo Syndrome Type B

Content Provider	PubMed Central
Author	Ohmi, Kazuhiro Zhao, Hui-zhi Neufeld, Elizabeth F.
Editor	Ginsberg, Stephen D.
Copyright Year	2011
Abstract	Sanfilippo syndrome type B (MPS IIIB) is characterized by profound mental retardation in childhood, dementia and death in late adolescence; it is caused by deficiency of α-N-acetylglucosaminidase and resulting lysosomal storage of heparan sulfate. A mouse model, generated by homologous recombination of the Naglu gene, was used to study pathological changes in the brain. We found earlier that neurons in the medial entorhinal cortex (MEC) and the dentate gyrus showed a number of secondary defects, including the presence of hyperphosphorylated tau (Ptau) detected with antibodies raised against Ptau in Alzheimer disease brain. By further use of immunohistochemistry, we now show staining in neurons of the same area for beta amyloid, extending the resemblance to Alzheimer disease. Ptau inclusions in the dentate gyrus of MPS IIIB mice were reduced in number when the mice were administered LiCl, a specific inhibitor of Gsk3β. Additional proteins found elevated in MEC include proteins involved in autophagy and the heparan sulfate proteoglycans, glypicans 1 and 5, the latter closely related to the primary defect. The level of secondary accumulations was associated with elevation of glypican, as seen by comparing brains of mice at different ages or with different mucopolysaccharide storage diseases. The MEC of an MPS IIIA mouse had the same intense immunostaining for glypican 1 and other markers as MPS IIIB, while MEC of MPS I and MPS II mice had weak staining, and MEC of an MPS VI mouse had no staining at all for the same proteins. A considerable amount of glypican was found in MEC of MPS IIIB mice outside of lysosomes. We propose that it is the extralysosomal glypican that would be harmful to neurons, because its heparan sulfate branches could potentiate the formation of Ptau and beta amyloid aggregates, which would be toxic as well as difficult to degrade.
Related Links	http://dx.doi.org/10.1371/journal.pone.0027461
Starting Page	27461
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	11
Volume Number	6
Language	English
Publisher	Public Library of Science
Publisher Date	2011-11-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Defects in the Medial Entorhinal Cortex and Dentate Gyrus in the Mouse Model of Sanfilippo Syndrome Type B

Development of Sensory, Motor and Behavioral Deficits in the Murine Model of Sanfilippo Syndrome Type B

Impaired Adult Neurogenesis in the Dentate Gyrus of a Triple Transgenic Mouse Model of Alzheimer's Disease

Upregulation of APP, ADAM10 and ADAM17 in the Denervated Mouse Dentate Gyrus

Stem- and Progenitor Cell Proliferation in the Dentate Gyrus of the Reeler Mouse

Reduced Rate of Neural Differentiation in the Dentate Gyrus of Adult Dysbindin Null (Sandy) Mouse

Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus

Outer layer of Vb neurons in medial entorhinal cortex project to hippocampal dentate gyrus in mice

Properties of Doublecortin-(DCX)-Expressing Cells in the Piriform Cortex Compared to the Neurogenic Dentate Gyrus of Adult Mice

Defects in the Medial Entorhinal Cortex and Dentate Gyrus in the Mouse Model of Sanfilippo Syndrome Type B

Similar Documents

Defects in the Medial Entorhinal Cortex and Dentate Gyrus in the Mouse Model of Sanfilippo Syndrome Type B

Development of Sensory, Motor and Behavioral Deficits in the Murine Model of Sanfilippo Syndrome Type B

Impaired Adult Neurogenesis in the Dentate Gyrus of a Triple Transgenic Mouse Model of Alzheimer's Disease

Upregulation of APP, ADAM10 and ADAM17 in the Denervated Mouse Dentate Gyrus

Stem- and Progenitor Cell Proliferation in the Dentate Gyrus of the Reeler Mouse

Reduced Rate of Neural Differentiation in the Dentate Gyrus of Adult Dysbindin Null (Sandy) Mouse

Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus

Outer layer of Vb neurons in medial entorhinal cortex project to hippocampal dentate gyrus in mice

Properties of Doublecortin-(DCX)-Expressing Cells in the Piriform Cortex Compared to the Neurogenic Dentate Gyrus of Adult Mice

Defects in the Medial Entorhinal Cortex and Dentate Gyrus in the Mouse Model of Sanfilippo Syndrome Type B