Behavioral effects of 6-hydroxydopamine-induced damage to nigro-striatal pathway and Locus coeruleus as a rodent model of Parkinson's disease.

Autor: Bustelli IB; Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, São Paulo, SP 01221-020, Brazil., Oliveira LM; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA., Correa-Netto NF; Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, São Paulo, SP 01221-020, Brazil., Stilhano RS; Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, São Paulo, SP 01221-020, Brazil., Caetano AL; Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, São Paulo, SP 01221-020, Brazil. Electronic address: ariadiny.caetano@fcmsantacasasp.edu.br.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2024 Mar 28; Vol. 462, pp. 114873. Date of Electronic Publication: 2024 Jan 23.
DOI: 10.1016/j.bbr.2024.114873
Abstrakt: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc), which leads to motor and non-motor symptoms (NMS). NMS can appear many years before the classical motor symptoms and are associated with the neurodegeneration of several nuclei; in this work, we highlight the neurodegeneration of Locus coeruleus (LC) in PD. The aim was to investigate the effects of depleting SNpc and LC catecholaminergic neurons on behavioral and neurobiological endpoints. Here we used 6-hydroxydopamine (6-OHDA) in order to induced neurotoxic damage in three independent experimental groups: SNpc lesion group, which 6-OHDA was injected into CPu (CPu-6-OHDA), LC lesion group, which 6-OHDA was injected directly on LC to selectively caused a damage on this nucleus (LC-6-OHDA), and the combined SNpc and LC lesion group (CL-6-OHDA). Next, the behavioral studies were performed using the Morris water maze (MWM), open field (OF), and elevated plus maze (EPM). After stereotaxic surgeries, the animals showed a loss of 67% and 77% of Tyrosine hydroxylase (TH) reactive neurons in the SNpc and LC, respectively. The behavioral analysis showed the anxiety-like behavior in CL-6-OHDA group in the EPM test; in the MWM test, the combined lesions (CL-6-OHDA) showed an impairment in memory acquisition and spatial memory; and no changes were observed in locomotor activity in all the tests. Furthermore, our investigation demonstrating the effects of depleting SN and LC catecholaminergic neurons on behavioral and neurobiological parameters. All these data together lead us to believe that a bilateral PD model including a LC bilateral degeneration is potentially a more accurate model to evaluate the NMS in the pathological development of the disease in rodents.
Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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