Changes in mRNA in the dorsal root ganglion after stroke and subcutaneous neurotrophin-3 infusion in elderly rats

Brain and spinal injury often impair sensorimotor processing in the spinal cord and reduce mobility. Cortical stroke in rats leads to long-term deficits in dexterity and walking. Subcutaneous neurotrophin-3 infusion initiated at a clinically-feasible time-point after injury improved walking and dexterity. We discovered that Neurotrophin-3 is transported in sensory afferents from muscles to the dorsal root ganglia. Using genome-wide RNA sequencing of the whole cervical level 6-8 dorsal root ganglia, we sought gene changes in afferent neurons that were present at two timepoints after stroke. RNA-Seq was performed on whole C6-8 dorsal root ganglia of rats from three different groups: naïve rats, rats after unilateral cortical stroke+vehicle infusion and rats after unilateral cortical stroke and NT3 infusion. Differential expression was analyzed between each of the groups.

脑与脊髓损伤常可损害脊髓内的感觉运动加工功能，降低机体活动能力。大鼠皮层脑卒中会引发灵巧运动与行走功能的长期缺陷。在损伤后临床可行的时间节点启动皮下神经营养因子-3（Neurotrophin-3, NT3）输注，能够改善大鼠的行走与灵巧运动功能。本研究发现，神经营养因子-3可通过感觉传入神经从肌肉转运至背根神经节（dorsal root ganglia）。我们针对完整的颈6-8节段背根神经节开展全基因组RNA测序，旨在探究脑卒中后两个时间点传入神经元的基因表达变化。本研究对三组大鼠的颈6-8全段背根神经节进行了RNA测序：未造模的正常大鼠、单侧皮层脑卒中+溶剂输注组大鼠，以及单侧皮层脑卒中+NT3输注组大鼠，并对各组间的差异基因表达进行了分析。