Characterization of spinal cord glial cells in a model of hindlimb unloading in mice

Chelyshev, Yu. A.; Muhamedshina, Y.O.; Povysheva, T.V.; Shaymardanova, G. F.; Rizvanov, Albert A.; Nigmetzyanova, M. V.; Tiapkina, O.V.; Bondarenko, Natalya; Nikolskiy, E. E.; Islamov, R. R.

doi:10.1016/j.neuroscience.2014.09.004

Cited by 28 publications

(21 citation statements)

References 34 publications

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“…Only cells with clearly outlined nuclei were considered. 5 Genuine colocalization was confirmed by viewing the localization of immunopositive cells on orthogonal projections of all 3 channels. The threshold for counting cells as colocalized was a coefficient of colocalization of ≥ 0.5.…”

Section: Immunofluorescence Methodsmentioning

confidence: 95%

Post–spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG

Povysheva

Шмаров

Logunov

et al. 2017

Journal of Neurosurgery: Spine

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OBJECTIVEThe most actively explored therapeutic strategy for overcoming spinal cord injury (SCI) is the delivery of genes encoding molecules that stimulate regeneration. In a mouse model of amyotrophic lateral sclerosis and in preliminary clinical trials in patients with amyotrophic lateral sclerosis, the combined administration of recombinant adenoviral vectors (Ad5-VEGF+Ad5-ANG) encoding the neurotrophic/angiogenic factors vascular endothelial growth factor (VEGF) and angiogenin (ANG) was found to slow the development of neurological deficits. These results suggest that there may be positive effects of this combination of genes in posttraumatic spinal cord regeneration. The objective of the present study was to determine the effects of Ad5-VEGF+Ad5-ANG combination therapy on motor function recovery and reactivity of astrocytes in a rat model of SCI.METHODSSpinal cord injury was induced in adult Wistar rats by the weight-drop method. Rats (n = 51) were divided into 2 groups: the experimental group (Ad5-VEGF+Ad5-ANG) and the control group (Ad5-GFP [green fluorescent protein]). Recovery of motor function was assessed using the Basso, Beattie, and Bresnahan scale. The duration and intensity of infectivity and gene expression from the injected vectors were assessed by immunofluorescent detection of GFP. Reactivity of glial cells was assessed by changes in the number of immunopositive cells expressing glial fibrillary acidic protein (GFAP), S100β, aquaporin 4 (AQP4), oligodendrocyte transcription factor 2, and chondroitin sulfate proteoglycan 4. The level of S100β mRNA expression in the spinal cord was estimated by real-time polymerase chain reaction.RESULTSPartial recovery of motor function was observed 30 days after surgery in both groups. However, Basso, Beattie, and Bresnahan scores were 35.9% higher in the Ad5-VEGF+Ad5-ANG group compared with the control group. Specific GFP signal was observed at distances of up to 5 mm in the rostral and caudal directions from the points of injection. A 1.5 to 2.0–fold increase in the number of GFAP+, S100β+, and AQP4+ cells was observed in the white and gray matter at a distance of up to 5 mm from the center of the lesion site in the caudal and rostral directions. At 30 days after injury, a 2-fold increase in S100β transcripts was observed in the Ad5-VEGF+Ad5-ANG group compared with the control group.CONCLUSIONSIntraspinal injection of recombinant adenoviral vectors encoding VEGF and ANG stimulates functional recovery after traumatic SCI. The increased number of S100β+ astrocytes induced by this approach may be a beneficial factor for maintaining the survival and function of neurons. Therefore, gene therapy with Ad5-VEGF+Ad5-ANG vectors is an effective therapeutic method for SCI treatment.

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Section: Immunofluorescence Methodsmentioning

confidence: 95%

Post–spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG

Povysheva

Шмаров

Logunov

et al. 2017

Journal of Neurosurgery: Spine

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“…Chelyshev and colleagues (81), in a hind limb‐unloading model of bone desorption, demonstrated damage to the spinal cord in addition to changes in the bones and muscles, which paralleled a decrease in spinal OGN expression. Furthermore, in a chronic depression model in mice, OGN expression decreased in the amygdala, an important regulator of emotional behavior in mice, showing higher immobility (and thus severely depressed mice), whereas control mice and stressed mice with lower immobility (less depressed mice) had similar OGN expression (82).…”

Section: Ogn In Diseasementioning

confidence: 99%

The diverse functions of osteoglycin: a deceitful dwarf, or a master regulator of disease?

2016

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Small leucine-rich proteoglycans are emerging as important regulatory proteins within the extracellular matrix, where they exert both structural and nonstructural functions and hence are modulators of numerous biological processes, such as inflammation, fibrosis, and cell proliferation. One proteoglycan in particular, osteoglycin (OGN), also known as mimecan, shows great structural and functional diversity in normal physiology and in disease states, therefore making it a very interesting candidate for the development of novel therapeutic strategies. Unfortunately, the literature on OGN is confusing, as it has different names, and different transcript and protein variants have been identified. This review will give a clear overview of the different structures and functions of OGN that have been identified to date, portray its central role in pathophysiology, and highlight the importance of posttranslational processing, such as glycosylation, for the diversity of its functions.-Deckx, S., Heymans, S., Papageorgiou, A.-P. The diverse functions of osteoglycin: a deceitful dwarf, or a master regulator of disease? FASEB J. 30, 2651-2661 (2016). www.fasebj.orgThe extracellular matrix is a complex network of structural and nonstructural matrix proteins with a fundamental role in development, homeostasis, and pathophysiology. Small leucine-rich proteoglycans (SLRPs) are proteoglycans present in the extracellular matrix, where they are involved in a wide range of processes such as inflammation, fibrosis, and cell proliferation (1-4). Given the diversity of SLRPs, these proteoglycans are interesting targets for matrix-related research. In particular, osteoglycin (OGN), a class III SLRP member with multiple glycosylation sites, has been shown to be involved in many physiological processes (e.g., collagen fibrillogenesis, cell proliferation, and development), and in diverse pathologic entities, such as cardiovascular disease, cancer, and eye disease. Despite extensive research on OGN, the literature is rather confusing, because different names have been used for OGN, such as osteoinductive factor or mimecan, and different transcript and protein variants have been identified. Moreover, posttranslational processing, such as glycosylation, paramount in providing diversity in structure and function, is often poorly described. Hence, an identified function of OGN is rarely annotated to a certain transcript or glycosylated protein variant, adding to the confusion. Therefore, the purpose of this review is to give a clear overview of the different structures and functions of OGN known so far, highlight the importance of its glycosylation for the diversity in function, and describe its central role during normal physiology and in different pathological conditions. OGN: A DECEITFUL DWARFSLRPs have leucine-rich repeats (LRRs) (5), which are conserved motifs that are present from bacteria to humans and are critical for many processes, such as proteinprotein interactions, signal transduction, cell adhesion, and DNA repair (5). ...

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“…Moreover, Pmp22 exhibits a dose dependent function as both overexpression and deletion result in hereditary neuropathy (Han et al, 2013 ). Dhh is essential for the structural and functional integrity of the peripheral nerve (Sharghi-Namini et al, 2006 ) and Osteglycine, Claudin -19 and Smoothelin together with Pmp22 and Prx are associated with reduced myelination of the spinal cord in the hypogravity motor syndrome (Chelyshev et al, 2014 ). Moreover, mutations in Mpz, Pmp22, Egr2, and Prx are associated with Charcot–Marie–Tooth neuropathy in which the over expression of these genes leads to defective myelination processes.…”

Section: Discussionmentioning

confidence: 99%

Muscle Expression of SOD1G93A Modulates microRNA and mRNA Transcription Pattern Associated with the Myelination Process in the Spinal Cord of Transgenic Mice

Dobrowolny

Bernardini

Martini

et al. 2015

Front. Cell. Neurosci.

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A crucial system severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues. One of the best examples of impaired interplay between muscle and nerve is Amyotrophic Lateral Sclerosis, a neurodegenerative disease characterized by degeneration of motor neurons and muscle atrophy. Increasing evidences suggest that damage to motor neurons is enhanced by alterations in the neighboring non-neuronal cells and indicate that altered skeletal muscle might be the source of signals that impinge motor neuron activity and survival. Here we investigated whether muscle selective expression of SOD1G93A mutant gene modulates mRNAs and miRNAs expression at the level of spinal cord of MLC/SOD1G93A mice. Using a Taqman array, the Affymetrix Mouse Gene 2.0 ST approach and the MiRwalk 2.0 database, which provides information on miRNA and their predicted target genes, we revealed that muscle specific expression of SOD1G93A modulates relevant molecules of the genetic and epigenetic circuitry of myelin homeostasis in spinal cord of transgenic mice. Our study provides insights into the pathophysiological interplay between muscle and nerve and supports the hypothesis that muscle is a source of signals that can either positively or negatively affect the nervous system.

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Characterization of spinal cord glial cells in a model of hindlimb unloading in mice

Cited by 28 publications

References 34 publications

Post–spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG

Post–spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG

The diverse functions of osteoglycin: a deceitful dwarf, or a master regulator of disease?

Muscle Expression of SOD1G93A Modulates microRNA and mRNA Transcription Pattern Associated with the Myelination Process in the Spinal Cord of Transgenic Mice

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