%0 Journal Article
%T Sensory neurons derived from diabetic rats have diminished internal Ca2+ stores linked to impaired re-uptake by the endoplasmic reticulum
%A Elena Zherebitskaya
%A Jason Schapansky
%A Eli Akude
%A Darrell R Smith
%J ASN Neuro
%D 2012
%I 
%R 10.1042/an20110038
%X 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¨C5-month-old STZ (streptozotocin)-diabetic rats (an experimental model of Type 1 diabetes) were cultured. At 1¨C2 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+ homoeo<1?show=[fo]?>stasis possibly triggered by sub-optimal SERCA activity that could contribute to the distal axonopathy observed in diabetes.
%K axon plasticity
%K diabetic neuropathy
%K dorsal root ganglia (DRG)
%K neurodegeneration
%K sarco/endoplasmic reticulum Ca2+-ATPase (SERCA)
%U http://www.asnneuro.org/an/004/e072/an004e072.htm