Doran Sarah J, Trammel Cassandra, Benashaski Sharon E, Venna Venugopal Reddy, McCullough Louise D
Departments of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030.
Departments of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030; Departments of Neurology, University of Connecticut Health Center, Farmington, CT 06030.
Behav Brain Res. 2015 Apr 15;283:154-61. doi: 10.1016/j.bbr.2015.01.035. Epub 2015 Jan 31.
Speech impairments affect one in four stroke survivors. However, animal models of post-ischemic vocalization deficits are limited. Male mice vocalize at ultrasonic frequencies when exposed to an estrous female mouse. In this study we assessed vocalization patterns and quantity in male mice after cerebral ischemia. FOXP2, a gene associated with verbal dyspraxia in humans, with known roles in neurogenesis and synaptic plasticity, was also examined after injury. Using a transient middle cerebral artery occlusion (MCAO) model, we assessed correlates of vocal impairment at several time-points after stroke. Further, to identify possible lateralization of vocalization deficits induced by left and right hemispheric strokes were compared. Significant differences in vocalization quantity were observed between stroke and sham animals that persisted for a month after injury. Injury to the left hemisphere reduced early vocalizations more profoundly than those to the right hemisphere. Nuclear expression of Foxp2 was elevated early after stroke (at 6h), but significantly decreased 24h after injury in both the nucleus and the cytoplasm. Neuronal Foxp2 expression increased in stroke mice compared to sham animals 4 weeks after injury. This study demonstrates that quantifiable deficits in ultrasonic vocalizations (USVs) are seen after stroke. USV may be a useful tool to assess chronic behavioral recovery in murine models of stroke.
言语障碍影响四分之一的中风幸存者。然而，缺血后发声缺陷的动物模型有限。当暴露于处于发情期的雌性小鼠时，雄性小鼠会发出超声波频率的声音。在本研究中，我们评估了脑缺血后雄性小鼠的发声模式和发声量。FOXP2是一种与人类言语失用症相关的基因，在神经发生和突触可塑性中具有已知作用，在损伤后也进行了检测。使用短暂性大脑中动脉闭塞（MCAO）模型，我们在中风后的几个时间点评估了发声障碍的相关因素。此外，为了确定由左、右半球中风引起的发声缺陷是否可能存在侧化，我们进行了比较。在中风动物和假手术动物之间观察到发声量存在显著差异，这种差异在损伤后持续了一个月。左半球损伤比右半球损伤更显著地减少了早期发声。中风后早期（6小时）Foxp2的核表达升高，但在损伤后24小时，其在细胞核和细胞质中的表达均显著下降。与假手术动物相比，中风小鼠在损伤后4周时神经元Foxp2表达增加。本研究表明，中风后可观察到超声波发声（USV）的可量化缺陷。USV可能是评估中风小鼠模型慢性行为恢复的有用工具。
