Silymarin recovers 6-hydroxydopamine-induced motor deficits in mice

2018 ◽  
Vol 118 ◽  
pp. 549-556 ◽  
Author(s):  
Catiuscia Molz de Freitas ◽  
Bárbara Nunes Krum ◽  
Ana Paula Chiapinotto Ceretta ◽  
Larissa Finger Schaffer ◽  
Elizete de Moraes Reis ◽  
...  
Keyword(s):  
Motor Deficits ◽  
6 Hydroxydopamine

scholarly journals In vivo electrophysiology of nigral and thalamic neurons in alpha-synuclein-overexpressing mice highlights differences from toxin-based models of parkinsonism

2013 ◽  
Vol 110 (12) ◽  
pp. 2792-2805 ◽  
Author(s):  
C. J. Lobb ◽  
A. K. Zaheer ◽  
Y. Smith ◽  
D. Jaeger
Keyword(s):  
Primary Motor Cortex ◽  
Alpha Synuclein ◽  
Motor Dysfunction ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Wild Type ◽  
Beta Oscillations ◽  
Nigrostriatal Dopamine ◽  
6 Hydroxydopamine

Numerous studies have suggested that alpha-synuclein plays a prominent role in both familial and idiopathic Parkinson's disease (PD). Mice in which human alpha-synuclein is overexpressed (ASO) display progressive motor deficits and many nonmotor features of PD. However, it is unclear what in vivo pathophysiological mechanisms drive these motor deficits. It is also unknown whether previously proposed pathophysiological features (i.e., increased beta oscillations, bursting, and synchronization) described in toxin-based, nigrostriatal dopamine-depletion models are also present in ASO mice. To address these issues, we first confirmed that 5- to 6-mo-old ASO mice have robust motor dysfunction, despite the absence of significant nigrostriatal dopamine degeneration. In the same animals, we then recorded simultaneous single units and local field potentials (LFPs) in the substantia nigra pars reticulata (SNpr), the main basal ganglia output nucleus, and one of its main thalamic targets, the ventromedial nucleus, as well as LFPs in the primary motor cortex in anesthetized ASO mice and their age-matched, wild-type littermates. Neural activity was examined during slow wave activity and desynchronized cortical states, as previously described in 6-hydroxydopamine-lesioned rats. In contrast to toxin-based models, we found a small decrease, rather than an increase, in beta oscillations in the desynchronized state. Similarly, synchronized burst firing of nigral neurons observed in toxin-based models was not observed in ASO mice. Instead, we found more subtle changes in pauses of SNpr firing compared with wild-type control mice. Our results suggest that the pathophysiology underlying motor dysfunction in ASO mice is distinctly different from striatal dopamine-depletion models of parkinsonism.

Effect of subthalamic nucleus lesions in a 6-hydroxydopamine–induced rat parkinsonian model: behavioral and biochemical studies

2006 ◽  
Vol 105 (2) ◽  
pp. 284-287 ◽  
Author(s):  
Yong Sup Hwang ◽  
Insop Shim ◽  
Bom Bee Lee ◽  
Jin Woo Chang
Keyword(s):  
Kainic Acid ◽  
Subthalamic Nucleus ◽  
Behavioral Changes ◽  
Motor Deficits ◽  
Biochemical Studies ◽  
Tissue Dissection ◽  
Neurochemical Changes ◽  
6 Hydroxydopamine ◽  
Behavioral Improvement ◽  
Globus Pallidus Externus

Object The purpose of this study was to determine whether subthalamic nucleus (STN) ablation caused by kainic acid can restore dopaminergic neurotransmission and improve motor deficits in a 6-hydroxydopamine (6-OHDA)–induced hemiparkinsonian model. Methods The authors investigated behavioral changes in rats displaying parkinsonian symptoms (6-OHDA–lesioned rats) after an STN lesion was created using kainic acid. They also measured levels of dopamine and its metabolites following tissue dissection. The results of this study showed that STN ablation led to behavioral improvement in parkinsonian motor deficits. Increased levels of dopamine were also observed in the striatum and globus pallidus externus (GPE). Conclusions The results indicate that creation of an STN lesion in this hemiparkinsonian rat model may counteract some of the neurochemical changes within the striatum and GPE caused by the 6-OHDA, and influence striatal dopaminergic metabolism.

scholarly journals Changes in day/night activity in the 6-OHDA-induced experimental model of Parkinson´s disease: Exploring prodromal biomarkers

2020 ◽  
Author(s):  
Catalina Requejo ◽  
Karmele Lopez de-Ipiña ◽  
José Ángel Ruiz-Ortega ◽  
Elsa Fernández ◽  
Pilar M. Calvo ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Motor Impairment ◽  
Experimental Models ◽  
Nigrostriatal System ◽  
Motor Deficits ◽  
Dark Phase ◽  
Suitable Model ◽  
Model Following ◽  
6 Hydroxydopamine

Abstract Background: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder for which there is not currently a cure and when it is clinically diagnosed is likely too late. The search for experimental models mimicking an early stage of PD before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal injection of 6-OHDA to detect and analyze physiological changes underlying prodromal PD. Methods: Rats were unilaterally injected with 6-OHDA or saline solution into the striatum and placed in enriched environment cages where the activity was monitored. After two weeks, the amphetamine test was performed before the sacrifice. Immunohistochemistry was developed for the morphological evaluation and western blot analysis to assess molecular changes. Results: Home-cage monitoring revealed behavioral changes in response to 6-OHDA administration including significant hyperactivity and hypoactivity during the light and dark phase respectively turning out in a change of the circadian timing. A preclinical stage of PD was functionally confirmed with the amphetamine test. Moreover, the loss of tyrosine hydroxylase expression was significantly correlated with the motor results, and 6-OHDA induced early proapoptotic events. Conclusions: Our findings provide evidence for a novel prodromal 6-OHDA model following a customized monitoring system that could give insights to detect non-motor deficits and molecular targets to test neuroprotective/neurorestorative agents.

scholarly journals Ceftriaxone Ameliorates Motor Deficits and Protects Dopaminergic Neurons in 6-Hydroxydopamine-Lesioned Rats

2011 ◽  
Vol 3 (1) ◽  
pp. 22-30 ◽  
Author(s):  
T. C. H. Leung ◽  
C. N. P. Lui ◽  
L. W. Chen ◽  
W. H. Yung ◽  
Y. S. Chan ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Motor Deficits ◽  
6 Hydroxydopamine

scholarly journals Chondroitinase ABC reduces dopaminergic nigral cell death and striatal terminal loss in a 6-hydroxydopamine partial lesion mouse model of Parkinson’s disease

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Edward J. R. Fletcher ◽  
Lawrence D. F. Moon ◽  
Susan Duty
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Chondroitin Sulphate ◽  
Neurological Injury ◽  
Substantia Nigra Pars Compacta ◽  
Motor Deficits ◽  
Chondroitinase Abc ◽  
Chondroitin Sulphate Proteoglycans ◽  
Partial Lesion ◽  
6 Hydroxydopamine

Abstract Background Parkinson’s disease (PD) is characterised by dopaminergic cell loss within the substantia nigra pars compacta (SNc) that leads to reduced striatal dopamine content and resulting motor deficits. Identifying new strategies to protect these cells from degeneration and retain striatal dopaminergic innervation is therefore of great importance. Chondroitin sulphate proteoglycans (CSPGs) are recognised contributors to the inhibitory extracellular milieu known to hinder tissue recovery following CNS damage. Digestion of these molecules by the bacterial lyase chondroitinase ABC (ChABC) has been shown to promote functional recovery in animal models of neurological injury. Although ChABC has been shown to promote sprouting of dopaminergic axons following transection of the nigrostriatal pathway, its ability to protect against nigrostriatal degeneration in a toxin-based module with better construct validity for PD has yet to be explored. Here we examined the neuroprotective efficacy of ChABC treatment in the full and partial 6-hydroxydopamine (6-OHDA) lesion mouse models of PD. Results In mice bearing a full 6-OHDA lesion, ChABC treatment failed to protect against the loss of either nigral cells or striatal terminals. In contrast, in mice bearing a partial 6-OHDA lesion, ChABC treatment significantly protected cells of the rostral SNc, which remained at more than double the numbers seen in vehicle-treated animals. In the partial lesion model, ChABC treatment also significantly preserved dopaminergic fibres of the rostral dorsal striatum which increased from 15.3 ± 3.5% of the intact hemisphere in saline-treated animals to 36.3 ± 6.5% in the ChABC-treated group. These protective effects of ChABC treatment were not accompanied by improvements in either the cylinder or amphetamine-induced rotations tests of motor function. Conclusions ChABC treatment provided significant protection against a partial 6-OHDA lesion of the nigrostriatal tract although the degree of protection was not sufficient to improve motor outcomes. These results support further investigations into the benefits of ChABC treatment for providing neuroprotection in PD.

scholarly journals Magnetothermal nanoparticle technology alleviates parkinsonian-like symptoms in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarah-Anna Hescham ◽  
Po-Han Chiang ◽  
Danijela Gregurec ◽  
Junsang Moon ◽  
Michael G. Christiansen ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Motor Behavior ◽  
Receptor Potential ◽  
Motor Deficits ◽  
Subcortical Structures ◽  
Hardware Failure ◽  
Implanted Electrodes ◽  
Therapeutic Benefits ◽  
6 Hydroxydopamine ◽  
Deep Brain

AbstractDeep brain stimulation (DBS) has long been used to alleviate symptoms in patients suffering from psychiatric and neurological disorders through stereotactically implanted electrodes that deliver current to subcortical structures via wired pacemakers. The application of DBS to modulate neural circuits is, however, hampered by its mechanical invasiveness and the use of chronically implanted leads, which poses a risk for hardware failure, hemorrhage, and infection. Here, we demonstrate that a wireless magnetothermal approach to DBS (mDBS) can provide similar therapeutic benefits in two mouse models of Parkinson’s disease, the bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and in the unilateral 6-hydroxydopamine (6-OHDA) model. We show magnetothermal neuromodulation in untethered moving mice through the activation of the heat-sensitive capsaicin receptor (transient receptor potential cation channel subfamily V member 1, TRPV1) by synthetic magnetic nanoparticles. When exposed to an alternating magnetic field, the nanoparticles dissipate heat, which triggers reversible firing of TRPV1-expressing neurons. We found that mDBS in the subthalamic nucleus (STN) enables remote modulation of motor behavior in healthy mice. Moreover, mDBS of the STN reversed the motor deficits in a mild and severe parkinsonian model. Consequently, this approach is able to activate deep-brain circuits without the need for permanently implanted hardware and connectors.

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