Melittin ameliorates motor function and prevents autophagy-induced cell death and astrogliosis in rat models of cerebellar ataxia induced by 3-acetylpyridine.


Journal

Neuropeptides
ISSN: 1532-2785
Titre abrégé: Neuropeptides
Pays: Netherlands
ID NLM: 8103156

Informations de publication

Date de publication:
Dec 2022
Historique:
received: 24 08 2022
revised: 10 10 2022
accepted: 11 10 2022
pubmed: 25 10 2022
medline: 15 11 2022
entrez: 24 10 2022
Statut: ppublish

Résumé

Cerebellar ataxia (CA) is a form of ataxia that adversely affects the cerebellum. This study aims to investigate the therapeutic effects of melittin (MEL) on a 3-acetylpyridine-induced (3-AP) cerebellar ataxia (CA) rat model. Initially, CA rat models were generated by 3-AP administration followed by the subcutaneous injection of MEL. The open-field test was used for the evaluation of locomotion and anxiety. Immunohistochemistry was also conducted for the autophagy markers of LC3 and Beclin1. In the next step, the morphology of the astrocyte, the cell responsible for maintaining homeostasis in the CNS, was evaluated by the Sholl analysis. The findings suggested that the administration of MEL in a 3-AP model of ataxia improved locomotion and anxiety (P < 0.001), decreased the expression of LC3 (P < 0.01) and Beclin1 (P < 0.05), increased astrocyte complexity (P < 0.05) and reduced astrocyte cell soma size (P < 0.001). Overall, the findings imply that the MEL attenuates the 3-AP-induced autophagy, causes cell death and improves motor function. As such, it could be used as a therapeutic procedure for CA due to its neuroprotective effects.

Sections du résumé

BACKGROUND BACKGROUND
Cerebellar ataxia (CA) is a form of ataxia that adversely affects the cerebellum. This study aims to investigate the therapeutic effects of melittin (MEL) on a 3-acetylpyridine-induced (3-AP) cerebellar ataxia (CA) rat model.
METHODS METHODS
Initially, CA rat models were generated by 3-AP administration followed by the subcutaneous injection of MEL. The open-field test was used for the evaluation of locomotion and anxiety. Immunohistochemistry was also conducted for the autophagy markers of LC3 and Beclin1. In the next step, the morphology of the astrocyte, the cell responsible for maintaining homeostasis in the CNS, was evaluated by the Sholl analysis.
RESULTS RESULTS
The findings suggested that the administration of MEL in a 3-AP model of ataxia improved locomotion and anxiety (P < 0.001), decreased the expression of LC3 (P < 0.01) and Beclin1 (P < 0.05), increased astrocyte complexity (P < 0.05) and reduced astrocyte cell soma size (P < 0.001).
CONCLUSIONS CONCLUSIONS
Overall, the findings imply that the MEL attenuates the 3-AP-induced autophagy, causes cell death and improves motor function. As such, it could be used as a therapeutic procedure for CA due to its neuroprotective effects.

Identifiants

pubmed: 36280441
pii: S0143-4179(22)00070-1
doi: 10.1016/j.npep.2022.102295
pii:
doi:

Substances chimiques

3-acetylpyridine 00QT8FX306
Beclin-1 0
Melitten 20449-79-0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

102295

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no conflict of interest.

Auteurs

Zahra Aghighi (Z)

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

Zeynab Ghorbani (Z)

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

Meysam Hassani Moghaddam (MH)

Department of Anatomical Sciences, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran.

Mobina Fathi (M)

Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Mohammad-Amin Abdollahifar (MA)

Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Mansoureh Soleimani (M)

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

Fariba Karimzadeh (F)

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

Homa Rasoolijazi (H)

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address: rasooli.h@iums.ac.ir.

Abbas Aliaghaei (A)

Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: abbas.aliaghaei@sbmu.ac.ir.

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Classifications MeSH