Effects of 6-hydroxydopamine-induced severe or partial lesion of the nigrostriatal pathway on the neuronal activity of pallido-subthalamic network in the rat

2007 ◽  
Vol 205 (1) ◽  
pp. 36-47 ◽  
Author(s):  
S BREIT ◽  
R BOUALIBENAZZOUZ ◽  
R POPA ◽  
T GASSER ◽  
A BENABID ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Nigrostriatal Pathway ◽  
Partial Lesion ◽  
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 ◽  
Author(s):  
Edward JR Fletc ◽  
Lawrence DF Moon ◽  
Susan Duty
Keyword(s):  
Chondroitin Sulphate ◽  
Neurological Injury ◽  
Substantia Nigra Pars Compacta ◽  
Motor Deficits ◽  
Protective Effects ◽  
Nigrostriatal Pathway ◽  
Chondroitinase Abc ◽  
Chondroitin Sulphate Proteoglycans ◽  
Partial Lesion ◽  
6 Hydroxydopamine

Abstract BackgroundParkinson'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. ResultsIn 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. ConclusionsChABC 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.

6-Hydroxydopamine Injections into the Nigrostriatal Pathway Attenuate Striatal Malonate and 3-Nitropropionic Acid Lesions

1998 ◽  
Vol 154 (2) ◽  
pp. 637-644 ◽  
Author(s):  
William F. Maragos ◽  
Rebekah J. Jakel ◽  
Zhen Pang ◽  
James W. Geddes
Keyword(s):  
Nigrostriatal Pathway ◽  
Nitropropionic Acid ◽  
6 Hydroxydopamine ◽  
3 Nitropropionic Acid

scholarly journals Adeno-Associated Viral Delivery of GDNF Promotes Recovery of Dopaminergic Phenotype following a Unilateral 6-Hydroxydopamine Lesion

2002 ◽  
Vol 11 (3) ◽  
pp. 215-227 ◽  
Author(s):  
John Mcgrath ◽  
Elishia Lintz ◽  
Barry J. Hoffer ◽  
Greg A. Gerhardt ◽  
E. Matthew Quintero ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Viral Vectors ◽  
Medial Forebrain Bundle ◽  
Therapeutic Potential ◽  
Clinical Situation ◽  
Dopamine Neurons ◽  
Nigrostriatal System ◽  
Nigrostriatal Pathway ◽  
Neurotoxic Lesion ◽  
6 Hydroxydopamine

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for dopamine neurons that has been proposed for use in the treatment of Parkinson's disease (PD). Previous studies using viral vectors to deliver GDNF in rodent models of PD have entailed administering the virus either prior to or immediately after neurotoxin-induced lesions, when the nigrostriatal pathway is largely intact, a paradigm that does not accurately reflect the clinical situation encountered with Parkinson's patients. In this study, recombinant adeno-associated virus carrying the gene encoding GDNF (rAAV-GDNF) was administered to animals bearing a maximal lesion in the nigrostriatal system, more closely resembling fully developed PD. Rats were treated with 6-hydroxydopamine into the medial forebrain bundle and assessed by apomorphine-induced rotational behavior for 5 weeks prior to virus administration. Within 4 weeks of a single intrastriatal injection of rAAV-GDNF, unilaterally lesioned animals exhibited significant behavioral recovery, which correlated with increased expression of dopaminergic markers in the substantia nigra, the medial forebrain bundle, and the striatum. Our findings demonstrate that rAAV-GDNF is capable of rescuing adult dopaminergic neurons from near complete phenotypic loss following a neurotoxic lesion, effectively restoring a functional dopaminergic pathway and diminishing motoric deficits. These data provide further support for the therapeutic potential of rAAV-GDNF-based gene therapy in the treatment of PD.

Locus ceruleus modulates migrating myoelectric complex in rats

1992 ◽  
Vol 262 (6) ◽  
pp. G1121-G1126 ◽  
Author(s):  
B. Bonaz ◽  
L. Martin ◽  
E. Beurriand ◽  
M. Manier ◽  
J. Hostein ◽  
...  
Keyword(s):  
Locus Ceruleus ◽  
Intracerebroventricular Injection ◽  
Conscious Rats ◽  
Migrating Myoelectric Complex ◽  
Cell Groups ◽  
Partial Lesion ◽  
Central Tegmental Tract ◽  
6 Hydroxydopamine ◽  
Bilateral Lesions

The role of the locus ceruleus (LC) in the control of migrating myoelectric complex (MMC) was investigated in rats with lesions induced by injections of 6-hydroxydopamine (6-OHDA). Control animals received the vehicle alone. MMC was recorded in conscious rats chronically fitted with electrodes. After 6-OHDA was injected into the LC, lesions of the LC were total, partial (mostly rostral), or ineffective. The MMC period was significantly longer in animals with a total or partial lesion but was unchanged in animals with an ineffective lesion. No lesion of other brain noradrenergic nuclei was observed. The longer MMC period is comparable to that obtained after intracerebroventricular injection of 6-OHDA, which is responsible for a more diffuse destruction of brain noradrenergic systems, including LC itself. Bilateral lesions of the central tegmental tract, which carries ascending noradrenergic axons from the medullary and pontine cell groups outside the LC, do not alter the MMC cycle. Consequently, the LC is most likely the major brain noradrenergic candidate for modulating the MMC pattern in rats.

scholarly journals The action of prolyl-leucyl-glycinamide (PLG) on the nigrostriatal pathway of the rat

1990 ◽  
Vol 48 (2) ◽  
pp. 156-160
Author(s):  
João S. Pereira ◽  
Luiz Augusto F. Andrade ◽  
Paulo H. F. Bertolucci ◽  
J. Geraldo Camargo Lima ◽  
Henrique B. Ferraz
Keyword(s):  
Wistar Rats ◽  
Electrolytic Lesion ◽  
Behavior Model ◽  
Low Doses ◽  
Nigrostriatal Pathway ◽  
Rem Sleep Deprivation ◽  
Hypothalamic Region ◽  
Male Wistar Rats ◽  
6 Hydroxydopamine ◽  
Higher Doses

In order to study the nigrostriatal pathway, we obtained the rotatory behavior model in male Wistar rats by electrolytic lesion of the left lateral hypothalamic region. Animals thus lesioned displayed rotations toward the same side of lesion when apomorphine was administered, a result in disagreement with what has been obtained in the model with 6-hydroxydopamine lesion. The administration of PLG alone was not followed by rotatory behavior but when the compound was administered in low doses (0.25 to 1mg/kg) simultaneously with apomorphine to animals previously submitted to REM sleep deprivation, a significant increase in the number of rotations was observed in comparison with controls and groups receiving higher doses of PLG. These results indicate that PLG may act as, a modulator on dopamine receptors in the striatum.

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