التفاصيل البيبلوغرافية
| العنوان: |
Sensory Neurons Derived from Diabetic Rats Have Diminished Internal Ca 2+ Stores Linked to Impaired Re-uptake by the Endoplasmic Reticulum |
| المؤلفون: |
Zherebitskaya, Elena, Schapansky, Jason, Akude, Eli, Smith, Darrell R, Van der Ploeg, Randy, Solovyova, Natasha, Verkhratsky, Alexei, Fernyhough, Paul |
| المصدر: |
ASN Neuro ; volume 4, issue 1, page AN20110038 ; ISSN 1759-0914 1759-0914 |
| بيانات النشر: |
SAGE Publications |
| سنة النشر: |
2012 |
| مصطلحات موضوعية: |
Neurology (clinical), General Neuroscience |
| الوصف: |
Distal symmetrical sensory neuropathy in diabetes involves the dying back of axons, and the pathology equates with axonal dystrophy generated under conditions of aberrant Ca 2+ signalling. Previous work has described abnormalities in Ca 2+ homoeostasis in sensory and dorsal horn neurons acutely isolated from diabetic rodents. We extended this work by testing the hypothesis that sensory neurons exposed to long-term Type 1 diabetes in vivo would exhibit abnormal axonal Ca 2+ homoeostasis and focused on the role of SERCA (sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase). DRG (dorsal root ganglia) sensory neurons from age-matched normal and 3–5-month-old STZ (streptozotocin)-diabetic rats (an experimental model of Type 1 diabetes) were cultured. At 1–2 days in vitro an array of parameters were measured to investigate Ca 2+ homoeostasis including (i) axonal levels of intracellular Ca 2+ , (ii) Ca 2+ uptake by the ER (endoplasmic reticulum), (iii) assessment of Ca 2+ signalling following a long-term thapsigargin-induced blockade of SERCA and (iv) determination of expression of ER mass and stress markers using immunocytochemistry and Western blotting. KCl- and caffeine-induced Ca 2+ transients in axons were 2-fold lower in cultures of diabetic neurons compared with normal neurons indicative of reduced ER calcium loading. The rate of uptake of Ca 2+ into the ER was reduced by 2-fold ( P<0.05) in diabetic neurons, while markers for ER mass and ER stress were unchanged. Abnormalities in Ca 2+ homoeostasis in diabetic neurons could be mimicked via long-term inhibition of SERCA in normal neurons. In summary, axons of neurons from diabetic rats exhibited aberrant Ca 2+ homoeostasis possibly triggered by suboptimal SERCA activity that could contribute to the distal axonopathy observed in diabetes. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1042/an20110038 |
| DOI: |
10.1042/AN20110038 |
| الإتاحة: |
https://doi.org/10.1042/an20110038Test |
| حقوق: |
http://journals.sagepub.com/page/policies/text-and-data-mining-licenseTest |
| رقم الانضمام: |
edsbas.8A40ADCE |
| قاعدة البيانات: |
BASE |
