Transection of preganglionic axons leads to CNS neuronal plasticity followed by survival and target reinnervation

Abstract

The goals of the present study were to investigate the changes in sympathetic preganglionic neurons following transection of distal axons in the cervical sympathetic trunk (CST) that innervate the superior cervical ganglion (SCG) and to assess changes in the protein expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB in the thoracic spinal cord. . At 1 week, a significant decrease in soma volume and reduced soma expression of choline acetyltransferase (ChAT) in the intermediolateral cell column (IML) of T1 spinal cord were observed, with both ChAT-ir and non-immunoreactive neurons expressing the injury marker activating transcription factor 3. . These changes were transient, and at later time points, ChAT expression and soma volume returned to control values and the number of ATF3 neurons declined. No evidence for cell loss or neuronal apoptosis was detected at any time point. Protein levels of BDNF and/or full length TrkB in the spinal cord were increased throughout the survival period. In the SCG, both ChAT-ir axons and ChAT protein remained decreased at 16 weeks, but were increased compared to the 10 week time point. These results suggest that though IML neurons show reduced ChAT expression and cell volume at 1 week following CST transection, at later time points, the neurons recovered and exhibited no significant signs of neurodegeneration. The alterations in BDNF and/or TrkB may have contributed to the survival of the IML neurons and the recovery of ChAT expression, as well as to the reinnervation of the SCG.

Regeneration of sensory but not motor axons following visceral nerve injury

“…Furthermore, there was no significant effect of injury on the number of retrogradely labelled motor neurons with injured pelvic ganglia, which is especially surprising given that these motor neurons remained chronically axotomised after transection. In support, other studies on injured visceral circuits support our findings by failing to demonstrate substantial loss of neurons after axotomy of autonomic preganglionic neurons or penis-projecting motor neurons (Coulibaly et al, 2013;Nangle and Keast, 2009;Palma and Keast, 2006;Peddie and Keast, 2011;Vizzard et al, 1995). The ability of pelvic motor neurons to survive axotomy is further indicated by their high survival rate following transplantation into the bladder wall .…”

Complementariness and Functional Parcellation of Neurotrophin Actions on the Oculomotor System

“…The increased expression of TrkB mRNA is indicative of an enhanced responsiveness of these motoneurons to BDNF after axon injury. Indeed, BDNF has been reported to exert important functions for the survival and regeneration of axotomized cranial and spinal motoneurons [1,66,79,85,86]. In contrast, the expression of the specific receptor for NT-3, TrkC, was downregulated in ocular motoneurons at the same post-lesion periods in which TrkB was upregulated ( Figure 3A).…”

“…The downregulation of the cholinergic phenotype is a commom phenomenon in lesioned motoneurons [60,86,91,99]. The time course evolution of choline acetyltransferase (ChAT) expression after enucleation (an initial decrease by day 15 followed by a recovery; Figure 3A We can conclude that extraocular motoneurons differentially modify their requirement of neurotrophins as a consequence of their target removal.…”

Distribution and phenotype of TrkB oligodendrocyte lineage cells in the adult rat spinal cord

“…For example the TrkB population in the ventral horn has been shown to exhibited plasticity following exercise (Skup et al, 2002), and TrkB cells in the IML, which houses sympathetic preganglionic neuronal cell bodies, were increased following distal transection of preganglionic axons (Coulibaly and Isaacson, 2012), possibly to contribute to neuronal survival and regeneration (Coulibaly et al, 2013). …”

“…Similarly, the majority of TrkB perineuronal cells in adult spinal cord expressed the OL phenotype and comprised approximately 15%-20% of all TrkB cells in the ventral horn. Portions of this study have been previously published in abstract form (Coulibaly and Isaacson, 2013). …”