Volume 29, Issue 3 (September 2025)                   Physiol Pharmacol 2025, 29(3): 260-271 | Back to browse issues page

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Mirehei M, Motamedi F, Maghsoudi N, Khodagholi F, Abbaszadeh F. The role of Bufexamac in reducing anxiety levels: focus on HPA axis dysfunction and neurotransmitter regulation in a rat model of Alzheimer’s disease. Physiol Pharmacol 2025; 29 (3) : 4
URL: http://ppj.phypha.ir/article-1-2413-en.html
The role of Bufexamac in reducing anxiety levels: focus on HPA axis dysfunction and neurotransmitter regulation in a rat model of Alzheimer’s disease
Monireh Mirehei , Fereshteh Motamedi , Nader Maghsoudi , Fariba Khodagholi , Fatemeh Abbaszadeh
Abstract:   (1248 Views)
Introduction: Alzheimer’s disease (AD) is a neurocognitive disorder characterized by neuropsychiatric symptoms (NPS), particularly anxiety. The underlying mechanisms involve disruptions in the hypothalamic-pituitary-adrenal (HPA) axis, and altered serotonergic signaling due to amyloid-beta (Aβ) accumu-lation. This study investigates the effects of Bufexamac, a Cyclooxygenase-2 (COX-2), and HDAC Class IIb inhibitor, on anxiety-like behaviors and neurochemical changes in a rat model of AD induced by Aβ. Methods: 18 adult Wistar rats were divided into three groups: Saline, Aβ, and Aβ + Bufexamac. Aβ25-35 was administered via intracerebroventricular injection, followed by daily Bufexamac treatment for eight days. Anxiety-like behaviors were assessed using the open-field test, while Western blotting and ELISA measured levels of glucocorticoid receptors (GR), corticotropin releasing factor (CRF), and serotonin in the amygdala. Results: Bufexamac significantly mitigated Aβ-induced anxiety-like behaviors, as evidenced by increased line crossings and time spent in the center of the arena (P<0.05). Western blot analysis revealed that Bufexamac reduced elevated GR levels in the Aβ group (P<0.05). Additionally, Bufexamac treat-ment significantly regulated serotonin (P<0.01) and CRF levels (P<0.05) in the amygdala compared to the Aβ group. Conclusion: Bufexamac effectively alleviates anxiety-like behaviors and restores neurochemical alterations in a rat model of AD, suggesting its potential as a possible therapeutic agent targeting neuropsychiatric symptoms associated with AD. Further research is warranted to explore its clinical applicability.
Article number: 4
Keywords: Alzheimer’s disease, Bufexamac, Glucocorticoid receptor, Serotonin, Histone deacetylase inhibitors
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Type of Manuscript: Experimental research article | Subject: Neurophysiology/Pharmacology
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