Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice.

Autor: Alzu'bi A; Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan. Electronic address: ayman.alzubi@yu.edu.jo., Abu-El-Rub E; Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan., Almahasneh F; Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan., Tahat L; Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 211-63, Jordan., Athamneh RY; Department of Medical Laboratory Sciences, Faculty of Allied Science, Zarqa University, Zarqa 13110, Jordan., Khasawneh R; Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan., Alzoubi H; Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan., Ghorab DS; Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan; Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Almazari R; Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan., Zoubi MSA; Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan., Al-Zoubi RM; Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar; Department of Biomedical Sciences, QU-Health, College of Health Sciences, Qatar University, Doha 2713, Qatar; Department of Chemistry, Jordan University of Science and Technology, P.O.Box 3030, Irbid 22110, Jordan. Electronic address: ralzoubi@hamad.qa.
Jazyk: angličtina
Zdroj: Neurotoxicology [Neurotoxicology] 2024 Jul; Vol. 103, pp. 50-59. Date of Electronic Publication: 2024 May 31.
DOI: 10.1016/j.neuro.2024.05.009
Abstrakt: Chronic use of synthetic cannabinoids (SCs) has been associated with cognitive and behavioural deficits and an increased risk of neuropsychiatric disorders. The underlying molecular and cellular mechanisms of the neurotoxic effects of long-term use of SCs have not been well investigated in the literature. Herein, we evaluated the in vivo effects of chronic administration of AB-FUBINACA on the hippocampus in mice. Our results revealed that the administration of AB-FUBINACA induced a significant impairment in recognition memory associated with histopathological changes in the hippocampus. These findings were found to be correlated with increased level of oxidative stress, neuroinflammation, and apoptosis markers, and reduced expression of brain-derived neurotrophic factor (BDNF), which plays an essential role in modulating synaptic plasticity integral for promoting learning and memory in the hippocampus. Additionally, we showed that AB-FUBINACA significantly decreased the expression of NR1, an important functional subunit of glutamate/NMDA receptors and closely implicated in the development of toxic psychosis. These findings shed light on the long-term neurotoxic effects of SCs on hippocampus and the underlying mechanisms of these effects. This study provided new targets for possible medical interventions to improve the treatment guidelines for SCs addiction.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ayman AlZu’bi reports financial support was provided by Yarmouk University.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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