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 the peripheral and central nervous system. The pathogenesis of these deficits is multifactorial, probably involving, among others, microvascular dysfunction and oxidative stress. The present study examined the effects of 12 weeks of treatment with a conjugate of the essential fatty acid gamma-linolenic acid and the anti-oxidant alpha-lipoic acid (GLA-LA) on functional deficits in the peripheral and central nervous system in streptozotocin-diabetic rats. Treatment was initiated 16 weeks after diabetes induction. Sciatic nerve motor and sensory conduction velocity, brainstem auditory evoked potentials and visual evoked potentials were measured in control, untreated and GLA-LA treated diabetic rats. Also, long-term potentiation, a form of synaptic 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 not reverse established deficits in nerve conduction velocity or in evoked potential latencies in diabetic rats. However, GLA-LA treatment did improve long-term potentiation in the hippocampus. It is concluded that GLA-LA, which is known to improve early deficits in peripheral nerve conduction in diabetic rats, is unable to reverse late deficits. However, the compound does reverse established deficits in long-term potentiation, suggesting that at least part of its activity is specifically directed at synaptic plasticity.
Biessels
G J
GJ
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, University Medical Center, Utrecht, The Netherlands. g.j.biessels@neuro.azu.nl
Smale
S
S
Duis
S E
SE
Kamal
A
A
Gispen
W H
WH
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002490:Central Nervous System / Q000187:drug effects* / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology*; D004359:Drug Therapy, Combination; D008297:Male; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D010525:Peripheral Nerves / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D008063:Thioctic Acid / Q000627:therapeutic use*; D017965:gamma-Linolenic Acid / Q000627:therapeutic use*
D001786:Blood Glucose; D008063:Thioctic Acid; D017965:gamma-Linolenic Acid