Brain proteoglycans in postnatal development and during behavior decline in senescence-accelerated OXYS rats

Рыкова, В. И.; Leberfarb, Elena Yu; Stefanova, Natalia A.; Shevelev, Oleg B.; Dymshits, G. M.; Kolosova, N. G.

doi:10.1134/s2079057012010134

Cited by 4 publications

(3 citation statements)

References 29 publications

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“…Tissue from the 60-year old autistic individual did not display reduced HS relative to its TD pair-member. However, HS levels declined sharply and systematically with increasing age for the 4 TD individuals, consistent with previous findings in both human and rodent brain tissue [29–31] and HS was extremely low in the 60-year old TD pair member, with levels converging for the two members of this pair. Thus, the lack of a substantial autistic-TD difference in this oldest pair appears to reflect this decline in HS with age, in the LV-SVZ for TD individuals.…”

Section: Discussionsupporting

confidence: 90%

Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles

Pearson¹,

Corley²,

Vasconcellos³

et al. 2013

Behavioural Brain Research

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Abnormal cellular growth and organization have been characterized in postmortem tissue from brains of autistic individuals, suggestive of pathology in a critical neurogenic niche, the subventricular zone (SVZ) of the brain lateral ventricles (LV). We examined cellular organization, cell proliferation, and constituents of the extracellular matrix such as N-sulfated heparan sulfate (HS) and laminin (LAM) in postmortem brain tissue from the LV-SVZ of young to elderly individuals with autism (n = 4) and age-matched typically developing (TD) individuals (n = 4) using immunofluorescence techniques. Strong and systematic reductions in HS immunofluorescence were observed in the LV-SVZ of the TD individuals with increasing age. For young through mature, but not elderly, autistic pair members, HS was reduced compared to their matched TDs. Cellular proliferation (Ki67+) was higher in the autistic individual of the youngest age-matched pair. These preliminary data suggesting that HS may be reduced in young to mature autistic individuals are in agreement with previous findings from the BTBR T+tf/J mouse, an animal model of autism; from mice with genetic modifications reducing HS; and with genetic variants in HS-related genes in autism. They suggest that aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism, and potentially involved in the etiology of the disorder.

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Section: Discussionsupporting

confidence: 90%

Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles

Pearson¹,

Corley²,

Vasconcellos³

et al. 2013

Behavioural Brain Research

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“…Indeed, GAGs were attributed amyloid modifying properties in vitro depending on the size (Vieira et al, 2014 ) and charge (Lawson et al, 2010 ) of the GAG chain. Given that the proteoglycan expression and GAG-composition are cell-specific and vary with brain development and senescence (Rykova et al, 2011 ), it can be speculated that ageing-related changes in cell-surface proteoglycan patterns will influence HSPG-mediated prion-like propagation.…”

Section: Amyloid Aggregationmentioning

confidence: 99%

Legal but lethal: functional protein aggregation at the verge of toxicity

Falsone

2015

Front. Cell. Neurosci.

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Many neurodegenerative disorders are linked to irreversible protein aggregation, a process that usually comes along with toxicity and serious cellular damage. However, it is emerging that protein aggregation can also serve for physiological purposes, as impressively shown for prions. While the aggregation of this protein family was initially considered exclusively toxic in mammalians organisms, it is now almost clear that many other proteins adopt prion-like attributes to rationally polymerize into higher order complexes with organized physiologic roles. This implies that cells can tolerate at least in some measure the accumulation of inherently dangerous protein aggregates for functional profit. This review summarizes currently known strategies that living organisms adopt to preserve beneficial aggregation, and to prevent the catastrophic accumulation of toxic aggregates that frequently accompany neurodegeneration.

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“…Recently Yuan et al 112 analyzed the proteome of early/middle-stage AMD, and the results were indicative of hematologic malfunctions, weakened ECM structural integrity and disrupted ECM cellular interactions. Given that OXYS rats exhibit significant changes in the content and composition of extracellular proteoglycans in the brain, 113 alterations of expression of genes regulating cell adhesion can be related to the systemic neurodegeneration observed in OXYS rats. 114 Summing up, our results indicate that combining different methods for reads counting is required for adequate detection of DE genes.…”

Section: Allmentioning

confidence: 99%

Rat retinal transcriptome: Effects of aging and AMD-like retinopathy

et al. 2013

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Pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, remains poorly understood due to the paucity of animal models that fully replicate the human disease. Recently, we showed that senescence-accelerated OXYS rats develop a retinopathy similar to human AMD. To identify alterations in response to normal aging and progression of AMD-like retinopathy, we compared gene expression profiles of retina from 3- and 18-mo-old OXYS and control Wistar rats by means of high-throughput RNA sequencing (RNA-Seq). We identified 160 and 146 age-regulated genes in Wistar and OXYS retinas, respectively. The majority of them are related to the immune system and extracellular matrix turnover. Only 24 age-regulated genes were common for the two strains, suggestive of different rates and mechanisms of aging. Over 600 genes showed significant differences in expression between the two strains. These genes are involved in disease-associated pathways such as immune response, inflammation, apoptosis, Ca ( 2+) homeostasis and oxidative stress. The altered expression for selected genes was confirmed by qRT-PCR analysis. To our knowledge, this study represents the first analysis of retinal transcriptome from young and old rats with biologic replicates generated by RNA-Seq technology. We can conclude that the development of AMD-like retinopathy in OXYS rats is associated with an imbalance in immune and inflammatory responses. Aging alters the expression profile of numerous genes in the retina, and the genetic background of OXYS rats has a profound impact on the development of AMD-like retinopathy.

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Brain proteoglycans in postnatal development and during behavior decline in senescence-accelerated OXYS rats

Cited by 4 publications

References 29 publications

Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles

Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles

Legal but lethal: functional protein aggregation at the verge of toxicity

Rat retinal transcriptome: Effects of aging and AMD-like retinopathy

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