Agomelatine attenuates cisplatin-induced cognitive impairment via modulation of BDNF/TrkB signaling in rat hippocampus

被引：8

作者：

Saral, Sinan ^{[1
]}

Topcu, Atilla ^{[2
]}

Alkanat, Mehmet ^{[3
]}

Mercantepe, Tolga ^{[4
]}

Sahin, Zafer ^{[5
]}

Akyildiz, Kerimali ^{[6
]}

Karatas, Kader Semra ^{[7
]}

Yildiz, Lamiye ^{[1
]}

Tumkaya, Levent ^{[4
]}

Yazici, Zihni Acar ^{[8
]}

机构：

[1] Recep Tayyip Erdogan Univ, Fac Med, Dept Physiol, Rize, Turkiye

[2] Recep Tayyip Erdogan Univ, Fac Med, Dept Pharmacol, Rize, Turkiye

[3] Giresun Univ, Fac Med, Dept Physiol, Giresun, Turkiye

[4] Recep Tayyip Erdogan Univ, Fac Med, Dept Histol & Embryol, Rize, Turkiye

[5] Karadeniz Tech Univ, Fac Med, Dept Physiol, Trabzon, Turkiye

[6] Recep Tayyip Erdogan Univ, Sch Healh Care Serv Vocat, Dept Med Serv & Tech, Rize, Turkiye

[7] Kutahya Hlth Sci Univ, Fac Med, Dept Mental Hlth & Dis, Kutahya, Turkiye

[8] Recep Tayyip Erdogan Univ, Fac Med, Dept Microbiol, Rize, Turkiye

来源：

JOURNAL OF CHEMICAL NEUROANATOMY | 2023年 / 130卷

关键词：

Agomelatine; Cisplatin; Memory; BDNF; nNOS; OXIDATIVE STRESS; BRAIN; BDNF; ANTIDEPRESSANT; NEUROTOXICITY; DYSFUNCTION; EXPRESSION;

D O I：

10.1016/j.jchemneu.2023.102269

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cisplatin is a drug used effectively in the treatment of malignant tumors. However, cisplatin has many side ef-fects, including cognitive impairment. Agomelatine, a synthetic melatonin analogue, is an important antide-pressant. Increasing evidence has shown that agomelatine may be a potential neuroprotective agent. The aim of this study was to investigate the effect of agomelatine on learning and memory functions in cisplatin-induced cognitive impairment in a rat model. Male rats were administered agomelatine and cisplatin for 4 weeks. Neurobehavioral tests were performed at the end of the 4th week. After behavioral tests, rats were euthanized and BDNF, TNF, IL-1 beta, MDA and GSH levels were measured in hippocampal homegenates by ELISA. In addition, nNOS and TrkB receptor activity were measured immunohistochemically. The results showed that agomelatine significantly improved cognitive functions in spatial memory tests in rats with cisplatin-induced cognitive impairment. In addition, agomelatine treatment positively affected the discrimination index (DI). On the other hand, agomelatine treatment elevated cisplatin-suppressed hippocampal BDNF levels. Agomelatine treatment reduced cisplatin-induced neuroinflammation by suppressing TNF and IL-1 beta levels. Similarly, agomelatine reduced oxidative stress in the hippocampus. Histological findings showed that agomelatine treatment reduced pyramidal neuron damage in hippocampal DG, CA1 and CA3. Cisplatin increased nNOS and TrkB positivity in DG, CA1 and CA3 neurons compared to control. In contrast, agomelatine treatment decreased both nNOS and TrkB positive scores. These findings indicate that agomelatine reduces cisplatin-related cognitive impairment by exerting anti-inflammatory action and possibly by the modulation of the BDNF/TrkB/nNOS pathways in the hippocampus.

引用

页数：11

共 45 条

[41] Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction [J].