BDNF prevents and reverses adult rat motor neuron degeneration and induces axonal outgrowth.
To assess the therapeutic potential of brain-derived neurotrophic factor (BDNF) in clinics, we extensively investigated the effects of BDNF on adult motor neurons in a rat spinal root avulsion model. Intrathecal administration of BDNF immediately after the spinal root avulsion greatly protected against the motor neuron cell death. BDNF also showed a protective effect on the atrophy of soma and on the reduction of transmitter-related enzymes such as choline acetyl transferase and acetylcholine esterase. Very interestingly, BDNF induced axonal outgrowth of severely damaged motor neurons at the avulsion site. The BDNF administration following 2-week treatment with phosphate-buffered saline after avulsion prevented further augmentation of cell death and reversed cholinergic transmitter-related enzyme deficiency. BDNF was demonstrated to possess a wide variety of biological effects on survival, soma size, cholinergic enzymes, and axonal outgrowth of adult motor neurons. These results provide a rationale for BDNF treatment in motor neuron diseases such as spinal cord injury and amyotrophic lateral sclerosis.
Kishino
A
A
Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
Ishige
Y
Y
Tatsuno
T
T
Nakayama
C
C
Noguchi
H
H
D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001369:Axons / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004334:Drug Administration Schedule; D005727:Ganglia, Spinal / Q000293:injuries* / Q000473:pathology; D007263:Infusions, Parenteral; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012183:Retrograde Degeneration / Q000187:drug effects*; D013116:Spinal Cord / Q000473:pathology; D013126:Spinal Nerve Roots / Q000293:injuries* / Q000473:pathology; D013346:Subarachnoid Space
D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase