The effect of gamma-linolenic acid-alpha-lipoic acid on functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats

Diabetes mellitus can lead to functional and structural deficits in both th e peripheral and central nervous system. The pathogenesis of these deficits is multifactorial, probably involving among others, microvascular dysfunct ion and oxidative stress. The present study examined the effects of 12 week s of treatment with a conjugate of the essential fatty acid gamma-linolenic acid and the anti-oxidant alpha-lipoic acid (GLA-LA) on functional deficit s in the peripheral and central nervous system in streptozotocin-diabetic r ats. Treatment was initiated 16 weeks after diabetes induction. Sciatic ner ve motor and sensory conduction velocity, brainstem auditory evoked potenti als and visual evoked potentials were measured in control, untreated and GL A-LA treated diabetic rats. Also, long-term potentiation, a form of synapti c plasticity used as a model for learning and memory at the cellular level, was examined in hippocampal slices. GLA-LA treatment (50 mg/kg/day) did no t reverse established deficits in nerve conduction velocity or in evoked po tential latencies in diabetic rats. However, GLA-LA treatment did improve l ong-term potentiation in the hippocampus. It is concluded that GLA-LA, whic h is known to improve early deficits in peripheral nerve conduction in diab etic rats, is unable to reverse late deficits. However, the compound does r everse established deficits in long-term potentiation, suggesting that at l east part of its activity is specifically directed at synaptic plasticity. (C) 2001 Elsevier Science B.V. All rights reserved.