Sysoev Yuri I, Shkorbatova Polina Y, Prikhodko Veronika A, Kalinina Daria S, Bazhenova Elena Y, Okovityi Sergey V, Bader Michael, Alenina Natalia, Gainetdinov Raul R, Musienko Pavel E
Department of Neuroscience, Sirius University of Science and Technology, Sirius 353340, Russia.
Pavlov Institute of Physiology of the RAS, Saint Petersburg 199034, Russia.
Int J Mol Sci. 2025 Mar 19;26(6):2761. doi: 10.3390/ijms26062761.
Spinal cord injury (SCI) affects millions of people worldwide. One of the main challenges of rehabilitation strategies is re-training and enhancing the plasticity of the spinal circuitry that was preserved or rebuilt after the injury. The serotonergic system appears to be crucial in these processes, since recent studies have reported the capability of serotonergic (5-HT) axons for axonal sprouting and regeneration in response to central nervous system (CNS) trauma or neurodegeneration. We took advantage of tryptophan hydroxylase 2 knockout (TPH2 KO) rats, lacking serotonin specifically in the brain and spinal cord, to study the role of the serotonergic system in the recovery of sensorimotor function after SCI. In the present work, we compared the rate of sensorimotor recovery of TPH2 KO and wild-type (WT) female rats after SCI (lateral hemisection at the T8 spinal level). SCI caused severe motor impairments in the ipsilateral left hindlimb, the most pronounced in the first week after the hemisection with gradual functional recovery during the following 3 weeks. The results demonstrate that TPH2 KO rats have less potential to recover motor functions since the degree of sensorimotor deficit in the tapered beam walking test (TBW) and ladder walking test (LW) was significantly higher in the TPH2 KO group in comparison to the WT animals in the 3rd and 4th weeks after SCI. The recovery dynamics of the hindlimb muscle tone and voluntary movements was in agreement with the restoration of motor performance in TBW and LW. Compound muscle action potential analysis in the gastrocnemius (GM) and tibialis (TA) muscles of both hindlimbs after electrical stimulation of the sciatic nerve or lumbar region (L5-L6) of the spinal cord indicated slower recovery of sensorimotor pathways in the TPH2 KO group versus their WT counterparts. In general, the observed results confirm the significance of central serotonergic mechanisms in the recovery of sensorimotor functions in rats and the relevance of the TPH2 KO rat model in studying the role of the 5-HT system in neurorehabilitation.
脊髓损伤（SCI）影响着全球数百万人。康复策略的主要挑战之一是重新训练并增强损伤后保留或重建的脊髓神经回路的可塑性。血清素能系统在这些过程中似乎至关重要，因为最近的研究报道了血清素能（5-羟色胺，5-HT）轴突在中枢神经系统（CNS）创伤或神经退行性变后具有轴突发芽和再生的能力。我们利用色氨酸羟化酶2基因敲除（TPH2 KO）大鼠（大脑和脊髓中特异性缺乏血清素）来研究血清素能系统在脊髓损伤后感觉运动功能恢复中的作用。在本研究中，我们比较了脊髓损伤（T8脊髓节段侧方半横切）后TPH2 KO和野生型（WT）雌性大鼠的感觉运动恢复率。脊髓损伤导致同侧左后肢严重运动障碍，在半横切后的第一周最为明显，随后3周功能逐渐恢复。结果表明，TPH2 KO大鼠恢复运动功能的潜力较小，因为在脊髓损伤后的第3周和第4周，与WT动物相比，TPH2 KO组在锥形梁行走试验（TBW）和阶梯行走试验（LW）中的感觉运动缺陷程度明显更高。后肢肌肉张力和自主运动的恢复动态与TBW和LW中运动表现的恢复一致。在坐骨神经或脊髓腰段（L5-L6）电刺激后，对双后肢腓肠肌（GM）和胫前肌（TA）进行复合肌肉动作电位分析表明，与WT大鼠相比，TPH2 KO组感觉运动通路的恢复较慢。总体而言，观察结果证实了中枢血清素能机制在大鼠感觉运动功能恢复中的重要性，以及TPH2 KO大鼠模型在研究5-HT系统在神经康复中的作用方面的相关性。
