Etanercept improves aging-induced cognitive deficits by reducing inflammation and vascular dysfunction in rats.

Autor: Gocmez SS; Kocaeli University Faculty of Medicine, Department of Pharmacology, Kocaeli, Turkey., Yazir Y; Kocaeli University Faculty of Medicine, Department of Histology and Embryology, Kocaeli, Turkey; Kocaeli University Center for Stem Cell and Gene Therapies Research and Practice, Institute of Health Sciences, Kocaeli, Turkey., Gacar G; Kocaeli University Center for Stem Cell and Gene Therapies Research and Practice, Institute of Health Sciences, Kocaeli, Turkey., Demirtaş Şahin T; Kocaeli University Faculty of Medicine, Department of Pharmacology, Kocaeli, Turkey., Arkan S; Kocaeli University Faculty of Medicine, Department of Physiology, Kocaeli, Turkey., Karson A; Kocaeli University Faculty of Medicine, Department of Physiology, Kocaeli, Turkey., Utkan T; Kocaeli University Faculty of Medicine, Department of Pharmacology, Kocaeli, Turkey; Kocaeli University Experimental Medical Research and Application Centre, Kocaeli, Turkey. Electronic address: tijenutkan@hotmail.com.
Jazyk: angličtina
Zdroj: Physiology & behavior [Physiol Behav] 2020 Oct 01; Vol. 224, pp. 113019. Date of Electronic Publication: 2020 Jun 20.
DOI: 10.1016/j.physbeh.2020.113019
Abstrakt: Normal aging may lead to cognitive deficits, which is associated with endothelial dysfunction and neuroinflammation. Dysregulation of TNFα expression contributes to vascular aging and dementia. In this study, we investigated the effects of etanercept, which is a TNFα inhibitor, on cognitive and endothelial function in aged rats. Male Wistar albino rats were divided into 3 groups: Young (4 month), aged (24 month) aged+ETA (24 month+etanercept). Etanercept (0.8 mg/kg/weekly) was given to the aged+ETA group subcutaneously for 8 weeks. Then passive avoidance test (PAT) and the Morris water maze test (MWMT) were used to evaluate cognitive functions of rats. After the behavioral tests, the rats were subjected to systolic blood pressure (SBP) measurement, and then endothelial function of thoracic aorta was evaluated by isolated organ bath system. Thoracic eNOS expression, hippocampal BDNF expression and serum and hippocampal TNF levels were also measured. In aged rats, it was shown that cognitive performances in MWMT and PAT were abolished whereas SBP unchanged. Furthermore, aging resulted in endothelial dysfunction, decreased expressions of thoracic eNOS and hippocampal BDNF, and increased level of TNF in serum and hippocampus. In contrast, ETA improved age-related cognitive deficits and endothelial dysfunction. In addition, ETA reversed changes in protein expression in aged rats. The results of this study indicate that ETA prevents cognitive deficits, endothelial dysfunction, peripheral and neuro-inflammation and decreament of neurotrophin expression in aged rats. These findings suggest that ETA may be beneficial with neuroprotective and vasculoprotective effects in elderly patients.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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