BDNF attenuates functional and structural disorders in nerves of galactose-fed rats.
Galactose intoxication of rats was used to disrupt metabolism of Schwann cells and skeletal muscle, two sites that contain the polyol-forming enzyme aldose reductase (AR). Galactose-fed rats develop a neuropathy characterized by nerve conduction deficits and axonal atrophy. To investigate the possibility that galactose metabolism by AR influences axonal function and structure by altering production of neurotrophic factors, the impact of galactose intoxication on nerve and muscle BDNF levels and the effects of exogenous BDNF treatment on galactose neuropathy were examined using biochemical, electrophysiologic and morphometric techniques. Galactose feeding increased BDNF protein in peripheral nerve and muscle. Exogenous BDNF treatment attenuated motor nerve conduction velocity deficits in the sciatic nerve of galactose-fed animals and myelin splitting of motor axons in the ventral root. In contrast, sensory nerve conduction velocity (SNCV) deficits in the sciatic nerve and myelin splitting in the central projections of sensory neurons were not prevented by BDNF treatment. BDNF treatment did not attenuate reduced axonal caliber in the sciatic nerve, but did ameliorate the diminution of the caliber of central sensory projections in the dorsal root. These findings point to the potential use of BDNF in the treatment of peripheral neuropathies.
Mizisin
A P
AP
Department of Pathology, University of California, San Diego, La Jolla 92093-0612, USA.
Bache
M
M
DiStefano
P S
PS
Acheson
A
A
Lindsay
R M
RM
Calcutt
N A
NA
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005690:Galactose; D009046:Motor Neurons / Q000187:drug effects / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000648:ultrastructure; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012584:Sciatic Nerve / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000648:ultrastructure
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D000449:Aldehyde Reductase; D005690:Galactose