Noradrenergic lesion of the locus coeruleus increases apomorphine-induced circling behavior and the firing activity of substantia nigra pars reticulata neurons in a rat model of Parkinson's disease

Wang, Yong; Zhang, Qiao Jun; Liu, Jian; Ali, Umar; Gui, Zhen; Hui, Yan Ping; Chen, Li; Wu, Zihui; Li, Qiang

doi:10.1016/j.brainres.2009.10.070

Cited by 37 publications

(26 citation statements)

References 56 publications

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“…In addition, NA seems to be involved also in modulating the activity of other types of neurons, such as SN pars reticulata neurons and cortical pyramidal neurons. For instance, bilateral lesions of LC NA neurons with 6-OHDA in DA lesioned rats increased the firing activity of SN pars reticulata neurons (Wang et al, 2010a) and medial prefrontal cortex pyramidal neurons (Wang et al, 2010b). In addition, firing rate of serotonin neurons (Haddjeri et al, 1996;Vandermaelen and Aghajanian, 1983;Svensson et al, 1975) and serotonin synthesis and release (Adell and Artigas, 1999;Pudovkina et al, 2002Pudovkina et al, , 2003Amargos-Bosch et al, 2003;Mongeau et al, 1997;Yoshioka et al, 1992) has been shown to be modified by NA input.…”

Section: Discussionmentioning

confidence: 99%

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Shin

Rogers

Devoto

et al. 2014

Experimental Neurology

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Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, studies of post-mortem PD brains have shown that not only DA neurons but also the noradrenergic (NA) neurons in the locus coeruleus degenerate, and that the NA neurodegeneration may be as profound, and also precede degeneration of the midbrain DA neurons. Previous studies in animal models of PD have suggested that loss of forebrain NA will add to the development of motor symptoms in animals with lesions of the nigrostriatal DA neurons, but the results obtained in rodents have been inconclusive due to the shortcomings of the toxin, DSP-4, used to lesion the NA projections. Here, we have developed an alternative double-lesion paradigm using injections of 6-OHDA into striatum in combination with intraventricular injections of a powerful NA immunotoxin, anti-DBH-Saporin, to eliminate the NA neurons in the brain.Animals with combined DA and NA lesions were more prone to develop L-DOPAinduced dyskinesia, even at low L-DOPA doses, and they performed significantly worse in tests of reflexive and skilled paw use, the stepping and staircase tests, compared to DA-only lesioned rats. Post-mortem analysis revealed that NA depletion did not affect the degree of DA depletion, or the loss of tyrosine hydroxylase-positive innervation in the striatum. Cell loss in the substantia nigra was similar in both single and double lesioned animals, showing that the worsening effect was not due to increased loss of nigral DA neurons. The results show that damage to the NA neurons in the central nervous system contributes to the development of motor impairments and the appearance of L-DOPAinduced dyskinesia in 6-OHDA lesioned rats, and provide support for the view that the development of motor symptoms and dyskinetic side effects in PD patients reflects the combined loss of midbrain DA neurons and NA neurons.3

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Section: Discussionmentioning

confidence: 99%

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Shin

Rogers

Devoto

et al. 2014

Experimental Neurology

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“…The eight regions targeted in each hemisphere were: rostral forelimb area (RFA; a rodent supplementary motor area), primary motor cortex (M1), dorsolateral striatum (DLS), dorsomedial striatum (DMS), GP, ventrolateral/ventroanterior nuclei of the thalamus (VL/ VA; projecting to motor cortex), STN, and substantia nigra pars reticulata (SNr). Center coordinates in relation to bregma and the cortical surface were in the following structures: Ϫ7.8 to Ϫ8.8 (Wang et al 2010). The implant was fixated with dental acrylic, which was attached to screws in the skull.…”

Section: Animalsmentioning

confidence: 99%

Systems-level neurophysiological state characteristics for drug evaluation in an animal model of levodopa-induced dyskinesia

Tamté

Brys

Richter

et al. 2016

Journal of Neurophysiology

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Disorders affecting the central nervous system have proven particularly hard to treat, and disappointingly few novel therapies have reached the clinics in recent decades. A better understanding of the physiological processes in the brain underlying various symptoms could therefore greatly improve the rate of progress in this field. We here show how systems-level descriptions of different brain states reliably can be obtained through a newly developed method based on large-scale recordings in distributed neural networks encompassing several different brain structures. Using this technology, we characterize the neurophysiological states associated with parkinsonism and levodopa-induced dyskinesia in a rodent model of Parkinson's disease together with pharmacological interventions aimed at reducing dyskinetic symptoms. Our results show that the obtained electrophysiological data add significant information to conventional behavioral evaluations and hereby elucidate the underlying effects of treatments in greater detail. Taken together, these results potentially open up for studies of neurophysiological mechanisms underlying symptoms in a wide range of neurological and psychiatric conditions that until now have been very hard to investigate in animal models of disease.

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“…In addition, reducing LC function alone by lesioning LC neurons can produce motor symptoms that are observed in PD (Grimbergen et al, 2009;Wang et al, 2010). In support of the LC lesion studies and the consequence of reduced NE content, DBH knockout mice, which do not synthesize NE, also exhibit PD motor symptoms with age .…”

Section: Lc Altered Dopaminergic Behaviormentioning

confidence: 69%

“…There have been several studies to indicate the ability of LC noradrenergic neurons to modulate dopamine-induced behavior, especially when LC noradrenergic neurons are reduced (Antelman & Caggiula, 1977;Archer & Fredriksson, 2006;Chopin et al, 1999;Grimbergen et al, 2009;Taylor et al, 2009;Villegier et al, 2003;Wang et al, 2010). In addition, reducing LC function alone by lesioning LC neurons can produce motor symptoms that are observed in PD (Grimbergen et al, 2009;Wang et al, 2010).…”

Section: Lc Altered Dopaminergic Behaviormentioning

confidence: 99%

“…The SN and VTA also have β-, α 1 -and α 2 -AR binding sites (Szot, Personal communication;Boyajian et al, 1987;Hudson et al, 1992;Lee et al, 1998;Rainbow et al, 1984;Rosin et al, 1996;Scheinin et al, 1994;Strazielle et al, 1999). The LC directly innervates and modifies the activity of midbrain dopaminergic neurons; the loss of LC noradrenergic neurons results in altered activity of dopaminergic neurons (Collingridge et al, 1979;Grenhoff et al, , 1995Grenhoff & Svensson, 1989Guiard et al, 2008;Wang et al, 2010).…”

Section: Lc Innervation To Midbrain Dopaminergic Neuronsmentioning

confidence: 99%

See 1 more Smart Citation

The Noradrenergic System is a Major Component in Parkinson’s Disease

Szot¹,

Franklin²,

Raskind³

2011

Etiology and Pathophysiology of Parkinson's Disease

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Noradrenergic lesion of the locus coeruleus increases apomorphine-induced circling behavior and the firing activity of substantia nigra pars reticulata neurons in a rat model of Parkinson's disease

Cited by 37 publications

References 56 publications

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Systems-level neurophysiological state characteristics for drug evaluation in an animal model of levodopa-induced dyskinesia

The Noradrenergic System is a Major Component in Parkinson’s Disease

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