Modeling Parkinson's Disease in Rats: An Evaluation of 6-OHDA Lesions of the Nigrostriatal Pathway

Deumens, Ronald; Blokland, Arjan; Prickaerts, Jos

doi:10.1006/exnr.2002.7891

Cited by 675 publications

(485 citation statements)

References 64 publications

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“…SChI stimulation also increased rotational behavior, a phenotype often observed in mice rendered parkinsonian by a 6-OHDA lesion (57). These results suggest that the exaggerated beta oscillations in PD may reflect an uncontrolled expression of a normal dynamical state of the CBT network, a state that is directly modulated by SChI excitability.…”

Section: M1 Superficialmentioning

confidence: 60%

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Kondabolu

Roberts

Bucklin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cortico-basal ganglia-thalamic (CBT) neural circuits are critical modulators of cognitive and motor function. When compromised, these circuits contribute to neurological and psychiatric disorders, such as Parkinson's disease (PD). In PD, motor deficits correlate with the emergence of exaggerated beta frequency (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) oscillations throughout the CBT network. However, little is known about how specific cell types within individual CBT brain regions support the generation, propagation, and interaction of oscillatory dynamics throughout the CBT circuit or how specific oscillatory dynamics are related to motor function. Here, we investigated the role of striatal cholinergic interneurons (SChIs) in generating beta and gamma oscillations in cortical-striatal circuits and in influencing movement behavior. We found that selective stimulation of SChIs via optogenetics in normal mice robustly and reversibly amplified beta and gamma oscillations that are supported by distinct mechanisms within striatal-cortical circuits. Whereas beta oscillations are supported robustly in the striatum and all layers of primary motor cortex (M1) through a muscarinic-receptor mediated mechanism, gamma oscillations are largely restricted to the striatum and the deeper layers of M1. Finally, SChI activation led to parkinsonianlike motor deficits in otherwise normal mice. These results highlight the important role of striatal cholinergic interneurons in supporting oscillations in the CBT network that are closely related to movement and parkinsonian motor symptoms.E xaggerated beta oscillations (15-30 Hz) within the cortico-basal ganglia-thalamic (CBT) neural network are putative electrophysiological correlates of bradykinesia and rigidity in Parkinson's disease (PD) (1-4). Therapies that effectively manage PD motor symptoms, such as dopamine replacement therapy and deep brain stimulation, are associated with a suppression of the exaggerated beta oscillations (4, 5). Beta oscillations are also found in the CBT circuits of patients with other movement-related disorders, such as epilepsy and dystonia (6, 7), and in normal, nonhuman primates (8, 9) and normal rodents (10, 11). Moreover, brief elevations (≤200 ms) of beta oscillations are observed in the basal ganglia of task-performing nonhuman primates and rodents during specific phases of behavioral tasks (10, 12, 13), indicating that beta oscillations may be important for motor and nonmotor functions. In contrast to the regulated temporal variability of beta oscillations in normal motor functions, temporal stability is correlated with the parkinsonian motor symptoms of bradykinesia and rigidity (2). Together, these findings suggest that brief epochs of beta oscillations are a normal aspect of basal ganglia dynamics, their temporal modulation is important for movement regulation, and loss of regulation or uncontrolled expression of beta oscillations may contribute to movement deficits, such as those observed in PD.Despite the clear link bet...

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Section: M1 Superficialmentioning

confidence: 60%

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Kondabolu

Roberts

Bucklin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The 6-OHDA model involves injection of the toxin directly in the striatum or in median forebrain bundle to cause retrograde degeneration of substantia nigra neurons. 6-OHDA lesions causes slow and partial lesion of these neurons over 2 weeks and mimic the slow progression of PD (Beal, 2001;Deumens et al, 2002). Noradrenergic neurons are required to transport the 6-OHDA inside the brain and after further traversal into the substantia nigra, it selectively accumulates in, and is toxic to, dopaminergic neurons probably by generation of free radicals.…”

Section: Discussionmentioning

confidence: 99%

Neurobehavioral assessment of hydroalcoholic extract ofTrigonella foenum-graecumseeds in rodent models of Parkinson’s disease

Gaur

Bodhankar

Thakurdesai

2013

Pharmaceutical Biology

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Context: Neuroprotective therapy to rescue dopaminergic neurons is an important trait in the management of Parkinson's disease (PD).Objective: The present study identified and evaluated SFSE-T, a standardized hydroalcoholic extract of Trigonella foenum-graecum L. seeds (Fabaceae), in animal models of PD. Materials and methods: The identification of SFSE-T was carried out by high-performance liquid chromatography for the marker compound trigonelline (TGN). The effects of single dose oral treatment of SFSE-T (10, 30 or 100 mg/kg) were studied using animal models of PD, namely, 6-hydroxydopamine (6-OHDA)-induced unilateral lesions in rats, and 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration in C57BL/6 mice. The effects of SFSE-T on monoamino oxidase (MAO) enzyme in vitro as well as possible side effects of SFSE-T in vivo were also evaluated. Results: The concentration of TGN in a test sample of SFSE-T was found to be 82%. SFSE-T (30 mg/kg, oral) showed a significant increase in the number of ipsilateral rotations (45.67 rotations in 30-min period) as compared with vehicle control group (no rotations) when tested in 6-OHDA-induced unilateral lesioned rats. SFSE-T (30 mg/kg, oral) showed significant reversal of motor dysfunction (spontaneous motor activity scores, speed, distance traveled and number of square crossed) caused by MPTP induced lesions in C57BL/6 mice in pretreatment (1 h) schedule but not in post-treatment (1 h) schedule. SFSE-T neither showed anticholinergic effects nor showed selective MAO-B enzyme inhibition in vitro. Discussion and conclusion: SFSE-T showed reversal of motor symptoms in an animal model of PD probably through neuroprotective properties. KeywordsAnimal model of disease, fenugreek, 6-hydroxydopamine lesions, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced neurotoxicity, neurodegenerative disease History

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“…For detecting the effect of estrogen in a PD model, experimental rats were treated with 6-OHDA, one of the neurotoxins most commonly used to model nigral degeneration experimentally (Deumens et al 2002). 6-OHDA (5.5 lL at 3.6 lg/mL) was dissolved in 2 mg/mL ascorbate-saline (0.2% ascorbic acid and 0.9% sodium chloride) as described previously (Zhou et al 2001) and unilaterally injected into the left medial forebrain bundle (MFB) of OVX rats.…”

Section: General Proceduresmentioning

confidence: 99%

Increased dopamine release in vivo by estradiol benzoate from the central amygdaloid nucleus of Parkinson's disease model rats

Liu

Xie

2004

Journal of Neurochemistry

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In addition to the dopaminergic neurons in the nigrostriatal system, the properties of dopaminergic neurons in the mesolimbic system, such as the amygdala, are also of interest and importance because of their specific neuromodulatory effects in the pathophysiology of Parkinson's disease (PD). Using the fast cyclic voltammetry (FCV) technique, we present evidence to indicate that electrically-evoked dopamine (DA) release from the amygdala, especially the central amygdaloid nucleus (CAN), of ovariectomized (OVX) female rats was significantly enhanced with increasing doses of estradiol benzoate (EB; 30, 50 and 100 lg/kg). Impaired DA release from the amygdala of an OVX rat PD model can also be increased by EB treatment (50 lg/kg) to a level similar to that of controls. The well established neuroprotective effects of estrogen may be beneficial for reducing the dysfunction of dopaminergic neurons in mesolimbic structures of rat PD models and PD patients.

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Modeling Parkinson's Disease in Rats: An Evaluation of 6-OHDA Lesions of the Nigrostriatal Pathway

Cited by 675 publications

References 64 publications

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Neurobehavioral assessment of hydroalcoholic extract ofTrigonella foenum-graecumseeds in rodent models of Parkinson’s disease

Increased dopamine release in vivo by estradiol benzoate from the central amygdaloid nucleus of Parkinson's disease model rats

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