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促性腺激素释放激素（GnRH）和/或生长激素（GH）对大鼠脊髓损伤后运动功能的神经营养和突触作用。

Neurotrophic and synaptic effects of GnRH and/or GH upon motor function after spinal cord injury in rats.

机构信息

Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, México.

Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, México.

出版信息

Sci Rep. 2024 Nov 2;14(1):26420. doi: 10.1038/s41598-024-78073-3.

DOI:10.1038/s41598-024-78073-3
PMID:39488642
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11531546/
Abstract

Thoracic spinal cord injury (SCI) profoundly impairs motor and sensory functions, significantly reducing life quality without currently available effective treatments for neuroprotection or full functional regeneration. This study investigated the neurotrophic and synaptic recovery potential of gonadotropin-releasing hormone (GnRH) and growth hormone (GH) treatments in ovariectomized rats subjected to thoracic SCI. Employing a multidisciplinary approach, we evaluated the effects of these hormones upon gene expression of classical neurotrophins (NGF, BDNF, and NT3) as well as indicative markers of synaptic function (Nlgn1, Nxn1, SNAP25, SYP, and syntaxin-1), together with morphological assessments of myelin sheath integrity (Klüver-Barrera staining and MBP immunoreactivity) and synaptogenic proteins (PSD95, SYP) by immunohystochemistry (IHC) , and also on the neuromotor functional recovery of hindlimbs in the lesioned animals. Results demonstrated that chronic administration of GnRH and GH induced notable upregulation in the expression of several neurotrophic and synaptogenic activity genes. Additionally, the treatment showed a significant impact on the restoration of functional synaptic markers and myelin integrity. Intriguingly, while individual GnRH application induced certain recovery benefits, the combined treatment with GH appeared to inhibit neuromotor recovery, suggesting a complex interplay in hormonal regulation post-SCI. GnRH and GH are bioactive and participate in modulating neurotrophic responses and synaptic restoration under neural damage conditions, offering insights into novel therapeutic approaches for SCI. However, the intricate effects of combined hormonal treatment accentuate the necessity for further investigation that conduce to optimal and novel therapeutic strategies for patients with spinal cord lesions.

摘要

胸段脊髓损伤（SCI）严重损害运动和感觉功能，极大地降低了生活质量，目前尚无有效的神经保护或完全功能再生治疗方法。本研究探讨了促性腺激素释放激素（GnRH）和生长激素（GH）治疗对去卵巢胸段 SCI 大鼠的神经营养和突触恢复潜力。采用多学科方法，我们评估了这些激素对经典神经营养因子（NGF、BDNF 和 NT3）以及突触功能标志物（Nlgn1、Nxn1、SNAP25、SYP 和 syntaxin-1）的基因表达的影响，以及形态学评估髓鞘完整性（Klüver-Barrera 染色和 MBP 免疫反应性）和突触形成蛋白（PSD95、SYP）的免疫组织化学（IHC），以及损伤动物后肢的运动神经功能恢复情况。结果表明，慢性 GnRH 和 GH 给药可显著上调几种神经营养和突触形成活性基因的表达。此外，该治疗对功能突触标志物和髓鞘完整性的恢复有显著影响。有趣的是，虽然单独应用 GnRH 诱导出某些恢复益处，但与 GH 联合治疗似乎抑制了运动神经恢复，表明在 SCI 后激素调节中存在复杂的相互作用。GnRH 和 GH 是生物活性的，参与调节神经损伤条件下的神经营养反应和突触恢复，为 SCI 的新治疗方法提供了新的见解。然而，联合激素治疗的复杂影响强调了进一步研究的必要性，以制定出针对脊髓损伤患者的最佳和新颖的治疗策略。

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