RNAseq dataset describing transcriptional changes in cervical sensory ganglia after bilateral pyramidotomy and forelimb intramuscular gene therapy with AAV1 encoding human neurotrophin-3

Abstract

Unilateral or bilateral corticospinal tract injury in the pyramids of adult rats causes changes in proprioceptive axon terminal arborization in the cervical spinal cord accompanied by hyperreflexia and abnormal movements including spasms [1, 2]. Treatment of affected forelimb muscles with an Adeno-Associated Viral Vector (AAV) encoding human neurotrophin-3 (NT3) normalizes many of these anatomical, neurophysiological and behavioural changes [1]. Interestingly, in several studies, neurotrophin-3 protein accumulates in cervical dorsal root ganglia (DRG) on the side ipsilateral to AAV injection [1, 3]. We hypothesize that neurotrophin-3 induces these changes (in proprioceptive axon wiring, proprioceptive reflex neurophysiology and sensorimotor behaviors involving proprioception) by modifying gene expression in affected cervical dorsal root ganglia (DRG). As a first step in testing this hypothesis, we analyzed the transcriptomes of cervical DRGs obtained during a previous study from naive rats and from rats after bilateral pyramidotomy (bPYX) with unilateral intramuscular injections of either AAV1-CMV-NT3 or AAV1-CMV-EGFP made 24h after injury [1]. Ten weeks after surgery, Poly(A) RNAs and small RNAs from C6 to C8 DRGs on the treated side were sequenced. We detected mRNAs or small RNAs that were significantly regulated under three conditions (bPYX+GFP vs naive; bPYX+NT3 versus naive; bPYX+NT3 vs bPYX+GFP). We identified mRNAs and small RNAs whose expression level was altered after pyramidotomy and normalized by neurotrophin-3 treatment. A bioinformatic analysis enabled us to identify genes that are likely to be expressed in proprioceptors after injury and which were regulated by neurotrophin-3 in the direction expected from other datasets involving knockout or overexpression of neurotrophin-3. This dataset will help us and others identify genes in sensory neurons whose expression levels are regulated by neurotrophin-3 treatment. This may help identify novel therapeutic targets to improve sensation and movement after neurological injury. Data has been deposited in the Gene Expression Omnibus (GSE82197).