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

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Gocmez S. S., Yazir Y., Gacar G., Demirtaş Şahin Ş., Arkan S., Karson A., ...Daha Fazla

Physiology & behavior, cilt.224, ss.113019, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 224
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.physbeh.2020.113019
  • Dergi Adı: Physiology & behavior
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index (SSCI), Scopus, Academic Search Premier, PASCAL, Animal Behavior Abstracts, Aquatic Science & Fisheries Abstracts (ASFA), Artic & Antarctic Regions, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Psycinfo, Veterinary Science Database
  • Sayfa Sayıları: ss.113019
  • Anahtar Kelimeler: Etanercept, TNF alpha, Learning, Memory, Aging, Vascular dementia, Inflammation, NECROSIS-FACTOR-ALPHA, TNF-ALPHA, CARDIOVASCULAR EVENTS, ALZHEIMERS-DISEASE, OXIDATIVE STRESS, RISK-FACTORS, DEMENTIA, EXPRESSION, IMPAIRMENT, PLASMA
  • Kocaeli Üniversitesi Adresli: Evet

Özet

Normal aging may lead to cognitive deficits, which is associated with endothelial dysfunction and neuroinflammation. Dysregulation of TNFa expression contributes to vascular aging and dementia. In this study, we investigated the effects of etanercept, which is a TNFa 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 agerelated 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.