Melatonin rescues pregnant female mice and their juvenile offspring from high fat diet-induced alzheimer disease neuropathy.

Autor:	Jan A; Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan., Shah M; Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan., Shah SA; Department of Biochemistry, Haripur University, Haripur, Pakistan., Habib SH; Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan., Ehtesham E; Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan., Ahmed N; Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Aug 24; Vol. 10 (17), pp. e36921. Date of Electronic Publication: 2024 Aug 24 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e36921
Abstrakt:	High fat diet (HFD) is a prime factor, which contributes to the present epidemic of metabolic syndrome. Prolonged intake of HFD induces oxidative stress (OS) that in turn causes neuroinflammation, neurodegeneration, insulin resistance, amyloid burden, synaptic dysfunction and cognitive impairment hence leading to Alzheimer's disease neuropathy. Melatonin (secreted by the Pineal gland) has the potential to nullify the toxic effects of reactive oxygen species (ROS) and have been shown to ameliorate various complications induced by HFD in rodent models. This study aimed to assess the neurotherapeutic effects of melatonin on HFD-induced neuroinflammation and neurodegeneration mediated by OS in pregnant female mice and their offspring. Western blotting, immunohistochemistry and antioxidant enzyme assays were used for quantification of samples from the hippocampal region of the brain of pregnant albino mice and their offspring. Short- and long-term memory was assessed by Y-maze and Morris Water Maze tests. HFD significantly induced OS leading to AD like neuropathology in the pregnant mice and their offspring while melatonin administration simultaneously with the HFD significantly prevented this neuropathy. This study reports that melatonin exerts these effects through the stimulation of SIRT1/Nrf2/HO-1 pathway that in turn reduces the HFD-induced OS and its downstream signaling. In conclusion melatonin prevents HFD-induced multiple complications that ultimately leads to the memory dysfunction in pregnant female mice and their successive generation via activation of SIRT1/Nrf2 signaling pathway. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors. Published by Elsevier Ltd.)
Databáze:	MEDLINE
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