Ferulic Acid-Loaded Nanostructure Maintains Brain Levels of ACh, Glutamate, and GABA and Ameliorates Anxiety and Memory Impairments Induced by the d-Galactose Aging Process in Rats

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Domenika R. Rossato, Jéssica L. O. Rosa, Murilo B. Fontoura, Leana E. M. de Souza, Tielle M. de Almeida, Kathiane B. Kudrna, Scheila R. Schaffazick, Cristiane B. da Silva, Letícia Birk, Sarah Eller, Tiago F. de Oliveira, Marilise E. Burger
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Abstract

Population aging is a global reality driven by increased life expectancy. This demographic phenomenon is intrinsically linked to the epidemic of cognitive disorders such as dementia and Alzheimer's disease, posing challenges for elderly and their families. In this context, the search for new therapeutic strategies to prevent or minimize cognitive impairments becomes urgent, as these deficits are primarily associated with oxidative damage and increased neuroinflammation. Ferulic acid (FA), a natural and potent antioxidant compound, is proposed to be nanoencapsulated to target the central nervous system effectively with lower doses and an extended duration of action. Here, we evaluated the effects of the nanoencapsulated FA on d-galactose (d-Gal)- induced memory impairments. Male Wistar adult rats were treated with ferulic acid-loaded nanocapsules (FA-Nc) or non-encapsulated ferulic acid (D-FA) for 8 weeks concurrently with d-Gal (150 mg/kg s.c.) injection. As expected, our findings showed that d-Gal injection impaired memory processes and increased anxiety behavior, whereas FA-Nc treatment ameliorated these behavioral impairments associated with the aging process induced by d-Gal. At the molecular level, nanoencapsulated ferulic acid (FA-Nc) ameliorated the decrease in ACh and glutamate induced by d-galactose (d-Gal), and also increased GABA levels in the dorsal hippocampus, indicating its therapeutic superiority. Additional studies are needed to elucidate the mechanisms underlying our current promising outcomes. Nanoscience applied to pharmacology can reduce drug dosage, thereby minimizing adverse effects while enhancing therapeutic response, particularly in neurodegenerative diseases associated with aging. Therefore, the strategy of brain-targeted drug delivery through nanoencapsulation can be effective in mitigating aging-related factors that may lead to cognitive deficits.

Graphical Abstract

阿魏酸负载的纳米结构可维持大鼠大脑中 ACh、谷氨酸和 GABA 的水平,并改善 D-半乳糖老化过程引起的焦虑和记忆损伤。
人口老龄化是预期寿命延长所导致的全球现实。这一人口现象与痴呆症和阿尔茨海默病等认知障碍的流行有着内在联系,给老年人及其家庭带来了挑战。在这种情况下,寻找新的治疗策略来预防或最大限度地减少认知障碍已成为当务之急,因为这些缺陷主要与氧化损伤和神经炎症加剧有关。阿魏酸(FA)是一种天然、强效的抗氧化化合物,有人建议将其纳米化,以更低的剂量和更长的作用时间有效地靶向中枢神经系统。在此,我们评估了纳米囊化 FA 对 d-半乳糖(d-Gal)诱导的记忆损伤的影响。雄性 Wistar 成年大鼠在注射 d-半乳糖(150 毫克/千克静脉注射)的同时,接受阿魏酸纳米胶囊(FA-Nc)或无胶囊阿魏酸(D-FA)治疗 8 周。正如预期的那样,我们的研究结果表明,注射d-Gal会损害记忆过程并增加焦虑行为,而FA-Nc治疗可改善这些与d-Gal诱导的衰老过程相关的行为损害。 在分子水平上,纳米阿魏酸胶囊(FA-Nc)可改善d-半乳糖(d-Gal)诱导的ACh和谷氨酸的减少,还可增加海马背侧的GABA水平,这表明它具有治疗优势。我们还需要进行更多的研究,以阐明目前取得的可喜成果背后的机制。将纳米科学应用于药理学可以减少药物剂量,从而最大限度地减少不良反应,同时提高治疗效果,尤其是在与衰老相关的神经退行性疾病方面。因此,通过纳米封装进行脑靶向给药的策略可以有效缓解可能导致认知障碍的衰老相关因素。
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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