Investigating the role of the brain-derived neurotrophic factor Val66Met polymorphism in repetitive mild traumatic brain injury outcomes in rats.

IF 4.7 2区心理学 Q1 BEHAVIORAL SCIENCES

Behavioral and Brain Functions Pub Date : 2025-03-05 DOI:10.1186/s12993-025-00270-5

Lauren P Giesler, William T O'Brien, Jesse Bain, Gershon Spitz, Emily J Jaehne, Maarten van den Buuse, Sandy R Shultz, Richelle Mychasiuk, Stuart J McDonald

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引用次数: 0

Abstract

Background: Mild traumatic brain injury (mTBI) poses a significant public health concern, particularly regarding repetitive injury, with outcomes ranging from acute neurobehavioral deficits to long-term impairments. While demographic factors like age and sex influence outcomes, the understanding of genetic contributions, particularly the role of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, remains limited. This study aimed to characterize acute effects of repetitive mTBI (rmTBI) in rats with the Val68Met SNP, the rodent equivalent of the human Val66Met, focusing on behavioral, fluid biomarker, and histological changes.

Methods: Using a closed-head injury model, rats underwent five mTBIs over consecutive days. Behavioral assessments included sensorimotor function, anxiety-like behavior, spatial learning and memory, and nociceptive response. Plasma neurofilament light (NfL) levels served as a biomarker of axonal injury and immunohistochemistry evaluated microglial activation.

Results: Sensorimotor deficits and increased anxiety-like behavior were found in rats with rmTBI, but these changes were not affected by sex or genotype. Plasma NfL levels were higher in rmTBI compared with sham rats, with levels greater in female rmTBI when compared with male rmTBI rats. Microglial activation was observed in the hypothalamus of injured rats, but was not influenced by genotype or sex.

Conclusions: While the Val68Met SNP did not significantly influence acute responses to rmTBI in this study, further investigation into alternative functional and pathophysiological outcomes, as well as long-term effects, is required.

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探讨脑源性神经营养因子Val66Met多态性在大鼠重复性轻度创伤性脑损伤预后中的作用。

背景：轻度创伤性脑损伤（mTBI）引起了重大的公共卫生关注，特别是关于重复性损伤，其结果从急性神经行为缺陷到长期损伤。虽然年龄和性别等人口统计学因素会影响结果，但对遗传因素的理解，特别是脑源性神经营养因子（BDNF） Val66Met多态性的作用仍然有限。本研究旨在表征具有Val68Met SNP（相当于人类Val66Met的啮齿动物）的大鼠的重复性mTBI （rmTBI）的急性效应，重点关注行为、液体生物标志物和组织学变化。方法：采用闭合性颅脑损伤模型，对大鼠进行连续5天的mtbi。行为评估包括感觉运动功能、焦虑样行为、空间学习记忆和伤害反应。血浆神经丝光（NfL）水平可作为轴突损伤的生物标志物，免疫组织化学可评估小胶质细胞的活化。结果：rmTBI大鼠存在感觉运动缺陷和焦虑样行为增加，但这些变化不受性别或基因型的影响。与假手术大鼠相比，rmTBI大鼠的血浆NfL水平更高，雌性rmTBI大鼠的血浆NfL水平高于雄性rmTBI大鼠。在损伤大鼠下丘脑观察到小胶质细胞的激活，但不受基因型和性别的影响。结论：虽然在本研究中，Val68Met SNP对rmTBI的急性反应没有显著影响，但需要进一步研究其他功能和病理生理结果以及长期影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Behavioral and Brain Functions 医学-行为科学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： A well-established journal in the field of behavioral and cognitive neuroscience, Behavioral and Brain Functions welcomes manuscripts which provide insight into the neurobiological mechanisms underlying behavior and brain function, or dysfunction. The journal gives priority to manuscripts that combine both neurobiology and behavior in a non-clinical manner.