title: NGF protects paravertebral but not prevertebral sympathetic neurons against exposure to high glucose in vitro.
abstract: In diabetes, sympathetic neuroaxonal dystrophy occurs in prevertebral celiac/superior mesenteric ganglia (CG/SMG) but not in paravertebral superior cervical ganglia (SCG). Changes in neurotrophic support by NGF occur during postnatal development and are implicated in diabetic neuropathy. Therefore, our aim was to compare the effects of age and NGF on the responses of CG/SMG and SCG neurons to high glucose levels in vitro. Neurons were dissociated from neonatal (5 days) and adult (12 weeks) rat ganglia and maintained in serum-free media containing glucose (10-100 mM) in the presence or absence of NGF (50 ng/ml) for 48 h. Cultures were immunostained for the pan neuronal marker, PGP9.5, and TUNEL. Neurons were assessed for viability, the presence of neurite outgrowth and for TUNEL-positive nuclei as a marker of apoptosis. Glucose caused significant concentration-dependent decreases in both viability and the proportion of neurons developing neurites together with significant increases in TUNEL-positive staining. Neonatal SCG neurons with neurites were significantly more susceptible to high glucose than adult SCG neurons whereas postnatal age had no influence on the response of CG/SMG neurons to high glucose. NGF protected adult SCG but not adult CG/SMG neurite-bearing neurons against the induction of TUNEL staining by high glucose. In the presence of NGF, CG/SMG neurons were markedly more susceptible to high glucose than SCG neurons. The greater susceptibility of CG/SMG neurons to diabetic neuropathy may be due to a selective inability of NGF to protect this particular population of sympathetic neurons against hyperglycaemia.
authors.affiliation: Research Department of Cell and Developmental Biology, Division of Biosciences, UCL, London, UK.
authors.forename: Yemane K
authors.initials: YK
authors.lastname: Semra
authors.forename: Sara
authors.initials: S
authors.lastname: Sherif
authors.forename: Jill
authors.initials: J
authors.lastname: Lincoln
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001342:Autonomic Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology* / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D043222:Ubiquitin Thiolesterase / Q000187:drug effects / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D020932:Nerve Growth Factor; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase