Survival of retinal ganglion cells in transgenic mice with deficiencies in sialyltransferases or neural cell adhesion molecule (NCAM) or after the administration of neuraminidase

Natalia Lobanovskaya,Monika Jürgenson,Külli Jaako,Anu Aonurm-Helm,Tamara Zharkovsky,Alexander Zharkovsky

doi:10.1186/2193-1801-4-s1-p24

Abstract

Neural cell adhesion molecule (NCAM) plays important roles in the regulation of the brain plasticity during its development and in adulthood. NCAM functions may be regulated by the addition of long linear homopolymers of alpha 2-8-linked sialic acid (PSA). PSA is attached to NCAM via either of two specific sialyltransferases: ST8SiaII and ST8SiaIV. PSA-NCAM is expressed abundantly in the retina and optic nerve during development and adulthood. In the retina PSA-NCAM is expressed in the glial cells in close proximity to retinal ganglion cell (RGC). The functions of the PSA-NCAM in the retina remain unknown. The aim of this study was to investigate the roles of PSA-NCAM in the survival of RGCs after administration of the exitotoxin kainic acid (KA). Intraocular administration of KA induced reduction in the density of RGCs approximately by 60%. Administration of endoneuraminidase (Endo-N) an enzyme, which removes PSA residues from the surface of NCAM, enhanced the toxic effect of KA on RGC. In knockout mice with constitutive deficiency of either ST8SiaII or ST8SiaIV genes, the levels of PSA-NCAM did not differ from those in wild type mice. The toxicity of KA on RGC in these animals also did not differ from control. It should be noted, however, that in knockout ST8SiaII-/- adult mice a reduced number of RGCs was found despite the presence of high levels of PSA-NCAM. These data suggest that during development ST8SiaII ensures high levels of PSA-NCAM, which necessary for the developmental survival of RGCs. The PSA-NCAM in the adult retina ensures the resistance of RGCs to injury.

Highlights

Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia
The results of the present study indicate that development of the neuronal hypoxic tolerance induced by the three-trial, in contrast to one-trial, mild hypoxic preconditioning is apparently largely associated with the activation of CREB, as well as brain-derived neurotrophic factor (BDNF) and Bcl-2 overexpression
No significant differences in serum level of Solubile form of RAGE (sRAGE) where found between rapidly progressing and slow progressing subgroup of multiple sclerosis (MS) patients.Our results suggest for the role of sRAGE in MS ethiopathogenesis, but we did not find any association of sRAGE in serum with the rate of MS disability progression

Summary

Introduction

Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia. The aim of the study was to characterize the effects of streptozocin (STZ)-indced diabetes on learning and memory of 5XFAD and wild-type (WT) mice in Morris water maze (MWM) at ages 2 and 6 months and on brain amyloid load. Existing evidence suggests GABAergic system is involved in pathophysiology of Alzheimer’s disease (AD) via inhibitory interneuron deficits (Verret et al, 2012) and decrease in functional GABAA receptors (Limon et al, 2012). Our concept: low doses of muscimol may prevent learning/memory deficits in intracerebroventricular (icv) streptozocin (STZ)-induced AD nontransgenic rat model. The Sigma-1 receptor is a chaperone protein that modulates intracellular calcium signalling of the endoplasmatic reticulum and is involved in learning and memory processes.The aim of the present study was to compare in vitro Ca2+ concentration modulating activity and in vivo behavioural effects of enantiomers of methylphenylpiracetam, a novel positive allosteric modulator of Sigma-1 receptors

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