Polysialic Acid in Brain Development and Synaptic Plasticity

Vaithianathan

J of Neuroscience Research

et al. 2015

Type 1 diabetes is associated with cognitive dysfunction. Cognitive processing, particularly memory acquisition, depends on the regulated enhancement of expression and function of glutamate receptor subtypes in the hippocampus. Impairment of memory was been detected in rodent models of type 1 diabetes induced by streptozotocin (STZ). This study examines the functional properties of synaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the expression of synaptic molecules that regulate glutamatergic synaptic transmission in the hippocampus of STZ-diabetic rats. The AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and single-channel properties of synaptosomal AMPA receptors were examined after 4 weeks of diabetes induction. Results show that amplitude and frequency of mEPSCs recorded from CA1 pyramidal neurons were decreased in diabetic rats. In addition, the singlechannel properties of synaptic AMPA receptors from diabetic rat hippocampi were different from those of controls. These impairments in synaptic currents gated by AMPA receptors were accompanied by decreased protein levels of AMPA receptor subunit GluR1, the presynaptic protein synaptophysin, and the postsynaptic anchor protein postsynaptic density protein 95 in the hippocampus of diabetic rats. Neural cell adhesion molecule (NCAM), an extracellular matrix molecule abundantly expressed in the brain, and the polysialic acid (PSA) attached to NCAM were also downregulated in the hippocampus of diabetic rats. Insulin treatment, when initiated at the onset of diabetes induction, reduced these effects. These findings suggest that STZinduced diabetes may result in functional deteriorations in glutamatergic synapses in the hippocampus of rats and that these effects may be reduced by insulin treatment. V C 2015 Wiley Periodicals, Inc.

Section: Discussionmentioning

confidence: 99%

Insulin treatment restores glutamate (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid) receptor function in the hippocampus of diabetic rats

Vaithianathan

J of Neuroscience Research

et al. 2015

“…Some examples where the role of glycans in ID is rather clear exist: the overmigration in α-dystroglycanopathies and importance of PSA in both neurogenesis (neurite outgrowth and axon pathfinding) and synaptogenesis/synaptic plasticity (Hildebrandt & Dityatev 2013) as described above. Interestingly, NCAM has many splice versions of which one of the three most prominent ones, NCAM-120, is GPI anchored to the membrane (Senkov et al 2012).…”

Section: Basis Of Clinical Presentationsmentioning

confidence: 99%

Neurological Aspects of Human Glycosylation Disorders

Freeze

Eklund²,

et al. 2015

Annu. Rev. Neurosci.

202

170

This review will present principles of glycosylation, describe the relevant glycosylation pathways and their related disorders, and highlight some of the neurological aspects and issues that continue to challenge researchers. Over 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. Most of these disorders impact the central and/or peripheral nervous systems. Patients typically have developmental delay/intellectual disability, hypotonia, seizures, neuropathy, and metabolic abnormalities in multiple organ systems. Between these disorders there is great clinical diversity because all cell types differentially glycosylate proteins and lipids. The patients have hundreds of mis-glycosylated products afflicting a myriad of processes including cell signaling, cell-cell interaction and cell migration. This vast complexity in glycan composition and function, along with limited analytic tools has impeded the identification of key glycosylated molecules that cause pathologies, and to date few critical target proteins have been pinpointed.

Journal of Biological Chemistry

“…Synthesis of 2,4,7,8,9-Pentaacetyl-3F ax -Neu5Ac-CO 2 Me (3F-NeuAc)-Methyl 5-acetetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-galactonon-2-enonate (23.8 g, 50.3 mmol, 1 eq) was dissolved in nitromethane (197 ml), and H 2 O (33 ml) was added. Select-Fluor (71.3 g, 201.2 mmol, 4 eq) was added, and the reaction was left to vigorously stir for 2 days at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…For example, as ligands for sialic acid binding proteins, sialosides mediate cellular homing and adhesion of leukocytes (3), modulation of immune responses (4), and adhesion of viral and bacterial pathogens to host cells (5). Sialosides also play key roles in fertilization (6), brain development (7), muscular function (8), and kidney function (9). Genetic deficiency in the cellular biosynthesis of sialic acid results in lethality during embryonic development in mice (10), highlighting the importance of sialic acid at the organismal level.…”

mentioning

confidence: 99%

Systemic Blockade of Sialylation in Mice with a Global Inhibitor of Sialyltransferases

Macauley

Arlian

Rillahan

et al. 2014

100

Background:In vivo pharmacological inhibition of sialyltransferases has, to date, not been possible. Results: 3F-NeuAc acts as a global sialyltransferase inhibitor in mice and causes kidney and liver dysfunction. Conclusion: Sialoside expression can be modulated in vivo with a sialyltransferase inhibitor. Significance: Pharmacological blockade of sialoside expression will be an important tool for future exploration of sialic acid in health and disease.