孟鲁司特减轻阿尔茨海默病Aβ1-42暴露模型小鼠记忆衰退、神经炎症和神经退行性生物标志物。

IF 3.3 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2025-08-07 DOI:10.1007/s00213-025-06865-0

Sneha Balki, Avtar Singh Gautam, Paul Gajanan Balaji, Awesh Kumar Yadav, Rakesh Kumar Singh

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引用次数: 0

摘要

阿尔茨海默病（AD）是老年患者认知和记忆能力下降的主要表现。虽然孟鲁司特传统上用于治疗哮喘，但其在预防AD的神经病理改变和记忆下降方面的作用最近在文献中有所报道。然而，由于孟鲁司特的血脑屏障渗透性差，口服孟鲁司特的脑可用性受到限制。本研究强调鼻内给药孟鲁司特可以在小鼠中提供相当大的孟鲁司特脑生物利用度。此外，在淀粉样β1-42 （a β1-42）诱导的AD动物模型中，经鼻给药孟鲁司特可显著改善空间和认知记忆，防止a β积累，星形胶质细胞活化，并改善海马和皮质区氧化还原平衡和神经元密度。这些神经保护作用被发现通过鼻内给药孟鲁司特比其口服给药在同等剂量下更好。这些结果表明，孟鲁司特可能通过鼻内给药，在阿尔茨海默病的病理生理上取得显著的治疗效果。

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Montelukast attenuated memory decline, neuroinflammatory and neurodegenerative biomarkers in Aβ_1-42 exposed model of alzheimer's disease in mice.

Alzheimer's disease (AD) represents major cognitive and memory decline in the elderly patients. Although Montelukast has traditionally been used for the treatment of asthma, its role in prevention of neuropathological changes and memory decline in AD have recently been reported in literature. However, the brain availability through oral administration of Montelukast is limited due to its poor blood-brain barrier permeation. This study has highlighted that the intranasal administration of Montelukast can provide a considerable brain bioavailability of Montelukast in mice. In addition, intranasal administration of Montelukast showed a significant improvement of spatial and cognitive memory, prevention of Aβ accumulation, astrocyte activation, along with improved redox balance and neuronal density in the hippocampus and cortex regions in the amyloid-beta_1-42 (Aβ_1-42)-induced animal model of AD. These neuroprotective effects were found to be better through intranasal administration of Montelukast in comparison to its oral administration at the equivalent dose. These results suggest that Montelukast may be administered through intranasal route to achieve a significant therapeutic effect in the pathophysiology of AD.

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.