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单次原发性爆炸暴露后啮齿动物的性别特异性差异:聚焦于单胺和甘丙肽系统。

Sex-Specific Differences in Rodents Following a Single Primary Blast Exposure: Focus on the Monoamine and Galanin Systems.

作者信息

Kawa Lizan, Arborelius Ulf P, Hökfelt Tomas, Risling Mårten

机构信息

Department of Neuroscience, Karolinska Institutet, Solna, Sweden.

出版信息

Front Neurol. 2020 Oct 15;11:540144. doi: 10.3389/fneur.2020.540144. eCollection 2020.

Abstract

Most blast-induced traumatic brain injuries (bTBI) are mild in severity and culpable for the lingering and persistent neuropsychological complaints in affected individuals. There is evidence that the prevalence of symptoms post-exposure may be sex-specific. Our laboratory has focused on changes in the monoamine and the neuropeptide, galanin, systems in male rodents following primary bTBI. In this study, we aimed to replicate these findings in female rodents. Brainstem sections from the locus coeruleus (LC) and dorsal raphe nuclei (DRN) were processed for hybridisation at 1 and 7 days post-bTBI. We investigated changes in the transcripts for tyrosine hydroxylase (TH), tryptophan hydroxylase two (TPH2) and galanin. Like in males, we found a transient increase in TH transcript levels bilaterally in the female LC. Changes in TPH2 mRNA were more pronounced and extensive in the DRN of females compared to males. Galanin mRNA was increased bilaterally in the LC and DRN, although this increase was not apparent until day 7 in the LC. Serum analysis revealed an increase in corticosterone, but only in exposed females. These changes occurred without any visible signs of white matter injury, cell death, or blood-brain barrier breakdown. Taken together, in the apparent absence of visible structural damage to the brain, the monoamine and galanin systems, two key players in emotional regulation, are activated deferentially in males and females following primary blast exposure. These similarities and differences should be considered when developing and evaluating diagnostic and therapeutic interventions for bTBI.

摘要

大多数爆炸所致创伤性脑损伤(bTBI)严重程度较轻,但却是受影响个体长期存在神经心理学主诉的原因。有证据表明,暴露后症状的发生率可能存在性别差异。我们实验室专注于原发性bTBI后雄性啮齿动物单胺和神经肽甘丙肽系统的变化。在本研究中,我们旨在在雌性啮齿动物中重复这些发现。在bTBI后1天和7天,对来自蓝斑(LC)和中缝背核(DRN)的脑干切片进行杂交处理。我们研究了酪氨酸羟化酶(TH)、色氨酸羟化酶2(TPH2)和甘丙肽转录本的变化。与雄性一样,我们发现雌性LC中双侧TH转录本水平短暂升高。与雄性相比,雌性DRN中TPH2 mRNA的变化更明显且更广泛。LC和DRN中双侧甘丙肽mRNA均增加,尽管LC中直到第7天才明显增加。血清分析显示皮质酮增加,但仅在暴露的雌性中出现。这些变化发生时没有任何白质损伤、细胞死亡或血脑屏障破坏的明显迹象。综上所述,在大脑明显没有可见结构损伤的情况下,单胺和甘丙肽系统这两个情绪调节的关键参与者,在原发性爆炸暴露后在雄性和雌性中被差异性激活。在开发和评估bTBI的诊断和治疗干预措施时,应考虑这些异同点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8055/7593658/4b3bd07db9c8/fneur-11-540144-g0001.jpg

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