Sex-differences in catecholamine transporter expression in the rodent prefrontal cortex following repetitive mild traumatic brain injury and methylphenidate treatment.

IF 3.7 2区医学 Q1 CLINICAL NEUROLOGY

International Journal of Neuropsychopharmacology Pub Date : 2025-09-22 DOI:10.1093/ijnp/pyaf070

Eleni Papadopoulos, Anna Abrimian, Christopher P Knapp, Jessica A Loweth, Barry D Waterhouse, Rachel L Navarra

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引用次数: 0

Abstract

Background: Irregular transmitter activity is theorized to underly impaired prefrontal cortex (PFC)-mediated executive functions following repetitive mild traumatic brain injury (rmTBI). The psychostimulant, methylphenidate (MPH), enhances catecholamine neurotransmission by blocking reuptake transporters and is used off-label to treat post-TBI executive dysfunction. Both rmTBI and MPH are known to independently alter catecholamine transporter levels.

Methods: The present report evaluated the interactive effects of rmTBI and a sub-chronic therapeutic dose of MPH on expression levels of vesicular monoamine transporter-2 (VMAT2) and norepinephrine reuptake transporter (NET) within the medial, anterior cingulate, and orbitofrontal subregions of the PFC in both male and female rats.

Results: MPH failed to rescue, and in some cases exacerbated, rmTBI-induced reductions in VMAT2 and NET expression in males, whereas transporter expression was largely unaltered in females.

Conclusion: These results suggest MPH treatment produces further protein-level perturbations of catecholaminergic activity that are proposed to underlie executive dysfunction in males, but negligible effects in females, following rmTBI.

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重复性轻度创伤性脑损伤和哌甲酯治疗后啮齿动物前额叶皮层儿茶酚胺转运体表达的性别差异。

背景：不规则的递质活动被认为是重复性轻度创伤性脑损伤（rmTBI）后前额叶皮质（PFC）介导的执行功能受损的潜在原因。精神兴奋剂哌醋甲酯（MPH）通过阻断再摄取转运体来增强儿茶酚胺的神经传递，并在标签外用于治疗脑外伤后的执行功能障碍。已知rmTBI和MPH都能独立改变儿茶酚胺转运蛋白水平。方法：本报告评估了rmTBI和亚慢性治疗剂量的MPH对雄性和雌性大鼠PFC内侧、前扣带和眶额亚区囊泡单胺转运蛋白-2 （VMAT2）和去甲肾上腺素再摄取转运蛋白（NET）表达水平的相互作用。结果：MPH未能挽救rmtbi诱导的雄性VMAT2和NET表达的减少，在某些情况下加重，而雌性转运蛋白表达基本不变。结论：这些结果表明，在rmTBI后，MPH治疗会产生进一步的蛋白质水平的儿茶酚胺活性扰动，这可能是男性执行功能障碍的基础，但对女性的影响可以忽略不计。

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

International Journal of Neuropsychopharmacology 医学-精神病学

CiteScore

8.40

自引率

2.10%

发文量

230

审稿时长

4-8 weeks

期刊介绍： The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.