Central Serotonin Deficiency Impairs Recovery of Sensorimotor Abilities After Spinal Cord Injury in Rats

Yuri I. Sysoev ^{1, 2}

Polina Y Shkorbatova ^{2, 3}

Veronika A. Prikhodko ⁴

Daria S Kalinina ^{1, 3, 5}

Elena Y Bazhenova ^{2, 3}

Sergey V. Okovityi ⁴

Michael Bader ⁶

Natalia Alenina ⁶

RAUL R. GAINETDINOV ³

Pavel E Musienko ^{1, 7, 8}

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Department of Neuroscience, Sirius University of Science and Technology, Sirius 353340, Russia

Pavlov Institute of Physiology of the RAS, Saint Petersburg 199034, Russia

Institute of Translational Biomedicine, Saint Petersburg State University, 7–9 Universitetskaya Emb., Saint Petersburg 199034, Russia

⁴

Department of Pharmacology and Clinical Pharmacology, Saint Petersburg State Chemical and Pharmaceutical University, Saint Petersburg 197022, Russia

⁵

Sechenov Institute of Evolutionary Physiology and Biochemistry of the RAS, Saint Petersburg 194223, Russia

⁶

Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany |

⁷

Federal Center of Brain Research and Neurotechnologies, Moscow 199330, Russia

⁸

Life Improvement by Future Technologies Center, Moscow 143025, Russia

Publication type: Journal Article

Publication date: 2025-03-19

MDPI

Journal: International Journal of Molecular Sciences

scimago Q1

SJR: 1.179

CiteScore: 8.1

Impact factor: 4.9

ISSN: 16616596, 14220067

DOI: 10.3390/ijms26062761

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Abstract

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.