Melatonin rescues the mice brain against cisplatin-induced neurodegeneration, an insight into antioxidant and anti-inflammatory effects
ORCID Identifiers
Document Type
Article
Source of Publication
Neurotoxicology
Publication Date
8-25-2021
Abstract
Herein, we evaluated the neuroprotective effect of melatonin against cisplatin-induced oxidative damage, neuroinflammation, and synaptic dysfunction in mice. Cisplatin was administered at a dose of 2 mg/kg for eleven consecutive days to induce symptoms of cognitive impairment and neurodegeneration, while melatonin was administered at a 20 mg/kg dose for thirty consecutive days. We used various experimental techniques such as western blotting, immunofluorescence analysis, and oxidative stress marker assays to support our notion. Moreover, for cognitive impairment, we conducted behavioral analyses such as Morris Water Maze (MWM) and Y-Maze tests. The results indicated that melatonin attenuated oxidative stress by upregulating the expression of NF-E2-related factor-2 (Nrf2) dependent anti-oxidative protein levels. Similarly, melatonin positively modulated the expression of Sirt1 (a member of the sirtuin family), Phospho-AMPKα (Thr172), peroxisome proliferator-activated receptor (PPARγ), PPAR gamma coactivator 1 alpha (PGC-1α) coupled to downregulation of neuroinflammatory mediators and markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). Moreover, melatonin significantly upregulated the expression of synaptic markers such as postsynaptic density protein -95 (PSD-95), synaptosomal-associated protein 23 (SNAP-23), and synaptophysin compared to the cisplatin alone group. Furthermore, the results of behavior tests suggested that melatonin significantly improved the cognitive functions of the cisplatin injected mice.
DOI Link
Publisher
Elsevier BV
Disciplines
Medicine and Health Sciences
Keywords
Cisplatin, chemotherapy, melatonin, neurodegeneration
Scopus ID
Recommended Citation
Zakria, Muhammad; Ahmad, Nasir; Al Kury, Lina; Alattar, Abdullah; Uddin, Zia; Siraj, Sami; Ullah, Shakir; Alshaman, Reem; Khan, Muhammad; and Shah, Fawad, "Melatonin rescues the mice brain against cisplatin-induced neurodegeneration, an insight into antioxidant and anti-inflammatory effects" (2021). All Works. 4454.
https://zuscholars.zu.ac.ae/works/4454
Indexed in Scopus
yes
Open Access
no