title: Afferent input modulates neurotrophins and synaptic plasticity in the spinal cord.
abstract: The effects of eliminating or decreasing neuromuscular activity on the expression of neurotrophins and associated molecules in the spinal cord and subsequent effects on spinal cord plasticity were determined. Spinal cord isolation (SI), which eliminates any supraspinal and peripheral monosynaptic input to the lumbar region but maintains the motoneuron-muscle connectivity, decreased the levels of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) mRNA and protein in the isolated segments. Synapsin I, an important mediator for the effects of BDNF on synaptic plasticity, also was lower in the lumbar region of SI rats. In contrast, the levels of BDNF, synapsin, and growth-associated protein (GAP-43) were increased in the cervical spinal cord enlargement rostral to the isolated region, most likely reflecting an increased use of the forelimbs in the SI rats. GAP-43 levels were also increased in the lumbar spinal cord region, probably associated with compensatory mechanisms related to the deafferentation. In a separate set of experiments, the soleus muscle was paralyzed unilaterally via intramuscular botulinum toxin type A (BTX-A) injection to determine the effects of reducing the propioceptive input, of this normally highly active muscle on neurotrophin expression in the spinal cord. BDNF and synapsin I mRNAs were lower and NT-3 levels were higher in the lumbar hemicord ipsilateral to the BTX-A injection. Combined, these results indicate that the level of supraspinal and muscle afferent input plays an important role in modulating the levels of BDNF and NT-3 in the spinal cord.
authors.affiliation: Department of Physiological Science, UCLA Brain Injury Research Center, Los Angeles, California 90095, USA. fgomezpi@ucla.edu
authors.forename: Fernando
authors.initials: F
authors.lastname: Gómez-Pinilla
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ying
authors.forename: Roland R
authors.initials: RR
authors.lastname: Roy
authors.forename: John
authors.initials: J
authors.lastname: Hodgson
authors.forename: V Reggie
authors.initials: VR
authors.lastname: Edgerton
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D066298:In Vitro Techniques; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation; D009465:Neuromuscular Agents / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D020933:Neurotrophin 3 / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D016704:Synapsins / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D009465:Neuromuscular Agents; D020933:Neurotrophin 3; D012333:RNA, Messenger; D016704:Synapsins; D019274:Botulinum Toxins, Type A