สืบค้นงานวิจัย
Histopathological defects in intestine in severe spinal muscular atrophy mice are improved by systemic antisense oligonucleotide treatment
Sintusek P. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Histopathological defects in intestine in severe spinal muscular atrophy mice are improved by systemic antisense oligonucleotide treatment
ผู้แต่ง / หัวหน้าโครงการ (EN): Sintusek P.
บทคัดย่อ (EN): Gastrointestinal (GI) defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA). Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN) protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON) designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome. © 2016 Sintusek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-84968867089&doi=10.1371%2fjournal.pone.0155032&partnerID=40&md5=538739f4300efda906fbab45bd154681
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): Survival of Motor Neuron 1 Protein
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
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การอ้างอิง

Sintusek P.. "Histopathological defects in intestine in severe spinal muscular atrophy mice are improved by systemic antisense oligonucleotide treatment". ไม่ระบุหน่วยงาน. ม.ป.ป.

Sintusek P.. "Histopathological defects in intestine in severe spinal muscular atrophy mice are improved by systemic antisense oligonucleotide treatment". ไม่ระบุหน่วยงาน. ม.ป.ป.. Print.



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Histopathological defects in intestine in severe spinal muscular atrophy mice are improved by systemic antisense oligonucleotide treatment
Sintusek P.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
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