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

<p dir="ltr">Chronic use of synthetic <u>cannabinoids</u> (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...

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Main Author: Ayman Alzu'bi (18192898) (author)
Other Authors: Ejlal Abu-El-Rub (5168183) (author), Fatimah Almahasneh (21633368) (author), Lena Tahat (18192907) (author), Rabaa Y. Athamneh (21842702) (author), Ramada Khasawneh (21633371) (author), Hiba Alzoubi (18001609) (author), Doaa S. Ghorab (18192913) (author), Rawan Almazari (21842705) (author), Mazhar Salim Al Zoubi (17863880) (author), Raed M. Al-Zoubi (2037490) (author)
Published: 2024
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_version_ 1864513542118440960
author Ayman Alzu'bi (18192898)
author2 Ejlal Abu-El-Rub (5168183)
Fatimah Almahasneh (21633368)
Lena Tahat (18192907)
Rabaa Y. Athamneh (21842702)
Ramada Khasawneh (21633371)
Hiba Alzoubi (18001609)
Doaa S. Ghorab (18192913)
Rawan Almazari (21842705)
Mazhar Salim Al Zoubi (17863880)
Raed M. Al-Zoubi (2037490)
author2_role author
author
author
author
author
author
author
author
author
author
author_facet Ayman Alzu'bi (18192898)
Ejlal Abu-El-Rub (5168183)
Fatimah Almahasneh (21633368)
Lena Tahat (18192907)
Rabaa Y. Athamneh (21842702)
Ramada Khasawneh (21633371)
Hiba Alzoubi (18001609)
Doaa S. Ghorab (18192913)
Rawan Almazari (21842705)
Mazhar Salim Al Zoubi (17863880)
Raed M. Al-Zoubi (2037490)
author_role author
dc.creator.none.fl_str_mv Ayman Alzu'bi (18192898)
Ejlal Abu-El-Rub (5168183)
Fatimah Almahasneh (21633368)
Lena Tahat (18192907)
Rabaa Y. Athamneh (21842702)
Ramada Khasawneh (21633371)
Hiba Alzoubi (18001609)
Doaa S. Ghorab (18192913)
Rawan Almazari (21842705)
Mazhar Salim Al Zoubi (17863880)
Raed M. Al-Zoubi (2037490)
dc.date.none.fl_str_mv 2024-06-08T06:00:00Z
dc.identifier.none.fl_str_mv 10.1016/j.neuro.2024.05.009
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Delineating_the_molecular_mechanisms_of_hippocampal_neurotoxicity_induced_by_chronic_administration_of_synthetic_cannabinoid_AB-FUBINACA_in_mice/29716265
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Neurosciences
Pharmacology and pharmaceutical sciences
Synthetic cannabinoids
AB-FUBINACA
Neurotoxicity
Recognition memory
Psychosis
Oxidative stress
dc.title.none.fl_str_mv Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">Chronic use of synthetic <u>cannabinoids</u> (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 <u>hippocampus</u> 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 <u>oxidative stress, neuroinflammation,</u> and apoptosis markers, and reduced expression of brain-derived neurotrophic factor (BDNF), which plays an essential role in modulating <u>synaptic plasticity</u> 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.</p><h2>Other Information</h2><p dir="ltr">Published in: NeuroToxicology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.neuro.2024.05.009" target="_blank">https://dx.doi.org/10.1016/j.neuro.2024.05.009</a></p>
eu_rights_str_mv openAccess
id Manara2_540aa57adb4ac9aa7c8137520cb3ce5e
identifier_str_mv 10.1016/j.neuro.2024.05.009
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/29716265
publishDate 2024
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rights_invalid_str_mv CC BY 4.0
spelling Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in miceAyman Alzu'bi (18192898)Ejlal Abu-El-Rub (5168183)Fatimah Almahasneh (21633368)Lena Tahat (18192907)Rabaa Y. Athamneh (21842702)Ramada Khasawneh (21633371)Hiba Alzoubi (18001609)Doaa S. Ghorab (18192913)Rawan Almazari (21842705)Mazhar Salim Al Zoubi (17863880)Raed M. Al-Zoubi (2037490)Biomedical and clinical sciencesNeurosciencesPharmacology and pharmaceutical sciencesSynthetic cannabinoidsAB-FUBINACANeurotoxicityRecognition memoryPsychosisOxidative stress<p dir="ltr">Chronic use of synthetic <u>cannabinoids</u> (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 <u>hippocampus</u> 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 <u>oxidative stress, neuroinflammation,</u> and apoptosis markers, and reduced expression of brain-derived neurotrophic factor (BDNF), which plays an essential role in modulating <u>synaptic plasticity</u> 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.</p><h2>Other Information</h2><p dir="ltr">Published in: NeuroToxicology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.neuro.2024.05.009" target="_blank">https://dx.doi.org/10.1016/j.neuro.2024.05.009</a></p>2024-06-08T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.neuro.2024.05.009https://figshare.com/articles/journal_contribution/Delineating_the_molecular_mechanisms_of_hippocampal_neurotoxicity_induced_by_chronic_administration_of_synthetic_cannabinoid_AB-FUBINACA_in_mice/29716265CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/297162652024-06-08T06:00:00Z
spellingShingle Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice
Ayman Alzu'bi (18192898)
Biomedical and clinical sciences
Neurosciences
Pharmacology and pharmaceutical sciences
Synthetic cannabinoids
AB-FUBINACA
Neurotoxicity
Recognition memory
Psychosis
Oxidative stress
status_str publishedVersion
title Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice
title_full Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice
title_fullStr Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice
title_full_unstemmed Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice
title_short Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice
title_sort Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice
topic Biomedical and clinical sciences
Neurosciences
Pharmacology and pharmaceutical sciences
Synthetic cannabinoids
AB-FUBINACA
Neurotoxicity
Recognition memory
Psychosis
Oxidative stress