Differential regulation of dendritic plasticity by neurotrophins following deafferentation of the adult spinal cord is independent of p75(NTR).

Spontaneous and/or treatment-evoked re-modeling of the CNS following spinal cord injury is a prerequisite for functional recovery. While there has been considerable interest in the role of endogenous neurotrophins in spontaneous plasticity of several populations of spinal axons, the same cannot be said for morphological changes to dendrites. Here, we examined the responses of dendrites in the mouse lateral spinal nucleus (LSN, a site of sensory integration in the dorsolateral white matter) to exogenous and endogenous neurotrophins. We performed a septuple dorsal rhizotomy, which permanently eliminates sensory input to the spinal cord, and stimulates sprouting of spinal axons. While dendrites showed no change in density following injury alone, they sprouted vigorously (a two-fold increase in density) upon addition of exogenous brain-derived neurotrophic factor (BDNF). On the other hand, endogenous nerve growth factor (NGF) severely restricted dendritic sprouting, as TrkA-Fc treatment also roughly doubled the density of dendritic processes in the LSN. Spontaneous, BDNF- and TrkA-Fc mediated sprouting was unaffected by the absence of p75(NTR). Importantly, TrkA-Fc treatment markedly reduced expression of the truncated BDNF receptor TrkBT1 in both p75(+/+) and p75(-/-) mice, which was robustly-upregulated by deafferentation in both genotypes. We propose that the upregulation of TrkBT1 by NGF results in a reduced availability of endogenous BDNF to dendrites. Accordingly, sprouting of serotonergic axons, a BDNF-dependent consequence of dorsal root injury, was significantly enhanced in TrkA-Fc-treated animals. These results suggest that NGF and BDNF signaling differentially regulates dendritic plasticity in the deafferented spinal cord.