Degeneration of the Golgi and neuronal loss in dorsal root ganglia in diabetic BioBreeding/Worcester rats.
OBJECTIVE
The aim of this study was to evaluate the nature and extent of neuronal loss in dorsal root ganglia (DRG) in diabetic polyneuropathy.


METHODS
We examined 10-month diabetic BioBreeding/Worcester (BB/Wor) rats with respect to DRG ultrastructure and morphometry, sural nerve morphometry, pro- and anti-apoptotic proteins, the expression of neurotrophic factors and their receptors, and sensory nerve functions.


RESULTS
In diabetic rats, DRG neurons decreased to 73% of normal, owing to loss of substance P and calcitonin gene-related peptide-positive neurons. Levels of pro-apoptotic active caspase-3, Bax and low-affinity nerve growth factor (NGF) were increased in DRG. The concentration of anti-apoptotic heat shock protein (HSP) 70 in DRG was decreased, whereas concentrations of Bcl-xl and HSP27 were unaltered. Levels of poly(ADP-ribose) polymerase (PARP) and cleaved PARP were unaltered. Levels of NGF in sciatic nerve and concentrations of the high-affinity NGF receptor, insulin receptor and IGF-I receptor in DRG were significantly decreased. Sensory nerve conduction velocity decreased to 78% of normal. Hyperalgesia increased up to 6 months. Myelinated and unmyelinated fibre numbers of the sural nerve were significantly decreased in diabetic rats. DRG examinations revealed no evidence of apoptosis, mitochondrial changes or abnormalities of the endoplasmic reticulum. Instead, neurons demonstrated progressive vacuolar degenerative changes of the Golgi apparatus, with fragmentation and formation of large cytoplasmic vacuoles. These data show that sustained apoptotic stress is present in DRG of chronically diabetic BB/Wor rats, but fails to proceed to apoptotic cell death.


CONCLUSIONS
Progressive DRG neuronal loss, particularly of small neurons, occurs in the type 1 diabetic BB/Wor rat. This is associated with neurotrophic withdrawal and progressive degeneration of the Golgi apparatus.
Kamiya
H
H
Department of Pathology, Wayne State University, School of Medicine, Scott Hall 9275, 540 E. Canfield Avenue, Detroit, MI 48201, USA.
Zhang
W
W
Sima
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AA
D000818:Animals; D001369:Axons / Q000473:pathology; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000473:pathology*; D005727:Ganglia, Spinal / Q000473:pathology*; D006056:Golgi Apparatus / Q000473:pathology*; D006614:Hindlimb / Q000294:innervation; D006358:Hot Temperature; D009414:Nerve Growth Factors / Q000032:analysis; D009474:Neurons / Q000473:pathology*; D011236:Prediabetic State / Q000473:pathology; D051381:Rats; D011913:Rats, Inbred BB; D017526:Receptor, IGF Type 1 / Q000032:analysis; D011972:Receptor, Insulin / Q000032:analysis; D012584:Sciatic Nerve / Q000473:pathology; D013373:Substance P / Q000032:analysis
D009414:Nerve Growth Factors; D013373:Substance P; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D015740:Calcitonin Gene-Related Peptide