Afferent Input Modulates Neurotrophins and Synaptic Plasticity in the Spinal Cord

Abstract

son, and V. Reggie Edgerton. Afferent input modulates neurotrophins and synaptic plasticity in the spinal cord. J Neurophysiol 92: 3423-3432, 2004; doi:10.1152/jn.00432.2004. 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 motoneuronmuscle 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.

Activity-Dependent Increase in Neurotrophic Factors Is Associated with an Enhanced Modulation of Spinal Reflexes after Spinal Cord Injury

“…Rehabilitative strategies routinely integrate activity-based therapies to induce repetitive activation of the neuromuscular system, to limit further structural/ anatomical loss and facilitate functional recovery. Activitydependent processes triggered by exercise affect multiple neurotrophic factors by increasing the level of brain-derived neurotrophic factor (BDNF; Dupont-Versteegden et al, 2004;Gomez-Pinilla et al, 2004;Hutchinson et al, 2004), glial cellderived neurotrophic factor (GDNF; Dupont-Versteegden et al, 2004), neurotrophin-3 (NT-3;Gomez-Pinilla et al, 2004;Hutchinson et al, 2004), and neurotrophin-4 (NT-4; Skup et al, 2002) in the spinal cord and hindlimb muscles. Neurotrophic factors are powerful regulators of neuronal survival, maintenance, and synaptic strength.…”

Spontaneous and Forced Exercise Promotes Cognitive Function and Expression of GAP-43 and NT-3 in the Hippocampus of Aged Rats

“…Even though NT-3 potentiates action potential-dependent excitatory synaptic activity (sEPSCs) and increases GAP-43 expression, NT-3 expression involves a very complicated process, which changes according to its subordinate activities 20) . At this point, the significant increase in the FE group has similarities to the expression pattern of GAP-43.…”

Sprouting, regeneration and circuit formation in the injured spinal cord: factors and activity

“…mRNA levels of BDNF receptor, synapsin I, GAP-43 and cyclic AMP response element binding protein (CREB) were also increased in the lumbar spinal cord after exercise. In turn, muscle paralysis by injection of botulinum-toxin A resulted in a decrease in BDNF and synapsin I in the spinal cord (Gomez-Pinilla et al 2004).…”