| Author/Editor | Zherebitskaya, Elena; Schapansky, Jason; Akude, Eli; Smith, Darell R; Van der Ploeg, Randy; Solovyova, Natasha; Verkhratsky, Alexei; Fernyhough, Paul | |
| Title | Sensory neurons derived from diabetic rats have diminished internal Ca2+ stores linked to impaired re-uptake by the endoplasmic reticulum | |
| Type | članek | |
| Vol. and No. | Letnik 4, št. 1 | |
| Publication year | 2012 | |
| Volume | str. 1-10 | |
| ISSN | 1759-0914 - ASN neuro | |
| Language | eng | |
| Abstract | Distal symmetrical sensory neuropathy in diabetes involves the dying back of axons, and the pathology equates with axonal dystrophy generated under conditions of aberrant Ca2+ signalling. Previous work has described abnormalities in Ca2+ 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 Ca2+ homoeostasis and focused on the role of SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-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 Ca2+ homoeostasis including (i) axonal levels of intracellular Ca2+, (ii) Ca2+ uptake by the ER (endoplasmic reticulum), (iii) assessment of Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ homoeostasis possibly triggered by sub-optimal SERCA activity that could contribute to the distal axonopathy observed in diabetes. | |
| Keywords | neuropathy diabetes sensory neurons nevropatija diabetes senzotični nevroni |