title: alpha-Lipoic acid corrects neuropeptide deficits in diabetic rats via induction of trophic support.
abstract: This study compared the effects of treatment of diabetic rats with either alpha-lipoic acid (100 mg/kg/day i.p. 5 days/week) or with recombinant human nerve growth factor (rhNGF; 0.2 mg/kg s.c. 3 days/week) on NGF-like immunoreactivity (NGFLI) and neuropeptide Y-like immunoreactivity (NPYLI) levels in the sciatic nerve and on the release of substance P-like immunoreactivity (SPLI) from the spinal cord in response to electrical stimulation of the dorsal roots in vitro. Diabetic rats showed depletion of NGFLI and NPYLI, together with reduced release of SPLI. Treatment with NGF increased the sciatic nerve NGFLI (to four times that seen in untreated diabetic rats) and normalised stimulus-evoked release of SPLI, but did not affect the sciatic nerve NPYLI. Treatment with alpha-lipoic acid caused a small non-significant increase in sciatic nerve NGFLI, but normalised both NPYLI levels and stimulus-evoked release of SPLI. These findings indicate that alpha-lipoic acid can boost neurotrophic support in diabetic rats, with effects beyond those related to NGF.
authors.affiliation: Department of Pharmacology, St. Bartholomew's, Queen Mary and Westfield College, London, UK.
authors.forename: N E
authors.initials: NE
authors.lastname: Garrett
authors.forename: M
authors.initials: M
authors.lastname: Malcangio
authors.forename: M
authors.initials: M
authors.lastname: Dewhurst
authors.forename: D R
authors.initials: DR
authors.lastname: Tomlinson
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000032:analysis / Q000494:pharmacology*; D009478:Neuropeptide Y / Q000032:analysis*; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D013373:Substance P / Q000378:metabolism; D008063:Thioctic Acid / Q000627:therapeutic use*
chemical_list: D009414:Nerve Growth Factors; D009478:Neuropeptide Y; D009479:Neuropeptides; D011994:Recombinant Proteins; D013373:Substance P; D008063:Thioctic Acid