Functional recovery and axonal growth following spinal cord transection is accelerated by sustained <scp>l</scp>‐DOPA administration

Doyle, Louise; Roberts, Barry L.

doi:10.1111/j.1460-9568.2004.03658.x

Cited by 12 publications

(3 citation statements)

References 41 publications

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“…2004). Furthermore, functional recovery and axonal growth after spinal cord transection are accelerated by sustained l ‐DOPA administration (Doyle and Roberts 2004).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of l‐DOPA on monoamine metabolism, cell survival and glutathione production in midbrain neuronal‐enriched cultures from parkin knockout and wild‐type mice

Casarejos

Solano

Menéndez

et al. 2005

Journal of Neurochemistry

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L-DOPA is the most effective treatment for Parkinson's disease but in isolated neuronal cultures it is neurotoxic for dopamine (DA) neurones. Experiments in vivo and clinical studies have failed to show toxicity of L-DOPA in animals or patients but that does not exclude the possibility of a toxic effect of L-DOPA on patients with certain genetic risk factors. Mutations of the parkin gene are the most frequent cause of hereditary parkinsonism. Parkin null mice have a mild phenotype that could be modified by different neurotoxins. The aim of this study was to investigate whether the toxic effects of L-DOPA on DA neurones are amplified in parkin null mice. We have measured the effects of L-DOPA on cell viability, tyrosine hydroxylase (TH) expression, DA metabolism and glutathione levels of parkin knockout (PK-KO) midbrain cultures. Neuronal-enriched cultures from PK-KO mice have similar proportions of the different cell types with the exception of a significant increment of microglial cells. L-DOPA (400 lM for 24 h) reduced the number of TH-immunoreactive cells to 50% of baseline and increased twofold the percentage of apoptotic cells in cultures of wild-type (WT) animals. The PK-KO mice, however, are not only resistant to the L-DOPA-induced pro-apoptotic effects but they have an increased number of TH-immunoreactive neurones after treatment with L-DOPA, suggesting that L-DOPA is toxic for neurones of WT mice but not those of parkin null mice. MAPK and phosphatidylinositol-3 kinase signalling pathways are not involved in the differential L-DOPA effects in WT and PK-KO cultures. Intracellular levels of L-DOPA were not different in WT and parkin null mice but the intracellular and extracellular levels of DA and 3-4-dihydroxyphenylacetic acid, however, were significantly increased in parkin null animals. Furthermore, monoamine oxidase activity was significantly increased in parkin null mice, suggesting that these animals have an increased metabolism of DA. The levels of glutathione were further increased in parkin null mice than in controls both with and without treatment with L-DOPA, suggesting that a compensatory mechanism may protect DA neurones from neuronal death. This study opens new avenues for understanding the mechanisms of action of L-DOPA on DA neurones in patients with Park-2 mutations.

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“…2004). Furthermore, functional recovery and axonal growth after spinal cord transection are accelerated by sustained l ‐DOPA administration (Doyle and Roberts 2004).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of l‐DOPA on monoamine metabolism, cell survival and glutathione production in midbrain neuronal‐enriched cultures from parkin knockout and wild‐type mice

Casarejos

Solano

Menéndez

et al. 2005

Journal of Neurochemistry

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“…For example, L-DOPA, a DA precursor (Fig. 1), enhances tail beat frequency and swimming speed in the European eel (Doyle & Roberts, 2004). L-DOPA also induced dominance in the Arctic charr (Salmonid), while high doses led to dyskinesia (Winberg and Nilsson, 1992).…”

Section: Dopamine and Locomotionmentioning

confidence: 98%

Dopaminergic systems in the European eel: characterization, brain distribution, and potential role in migration and reproduction

Sébert

Weltzien

Moisan³

et al. 2008

Hydrobiologia

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In fish like in mammals, dopamine (DA) is a major catecholaminergic neurotransmitter that contributes to many functions of the nervous system like sensory perception, tuning of sensori-motor cues, and hypothalamic and pituitary functions. In the eel, DA inhibits gonadal development, and juvenile silver eels remain blocked at a prepubertal stage if their reproductive migration does not occur. From data in other teleosts and vertebrates, it is suggested that DA would be involved also in the last steps of eel reproduction (oocyte maturation, ovulation, and spermiation) as well as in eel reproductive migration (locomotion and olfaction). Investigating dopaminergic systems in the eel may help in understanding the mechanisms of its complex life cycle and provide new data for its conservation and reproduction. In this article we review the biosynthesis and catabolism of catecholamines and discuss available methods to investigate brain dopaminergic systems in vertebrates and their application to the eel. Immunocytochemistry, in situ hybridization, and different tracing methods are used to map dopaminergic neurons and projections in the brain and pituitary and infer their potential functions. Moreover, variations in dopaminergic activity may be approached by means of quantitative methods like quantitative real-time RT-PCR and HPLC. These tools are currently used to study dopaminergic systems in the eel brain, their anatomy, regulation, and potential roles with special emphasis on the regulation of reproduction and reproductive migration.

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“…Treatments using quipazine (Antri et al, 2002; Barbeau and Rossignol, 1990; Feraboli-Lohnherr et al, 1999; Fong et al, 2005; Guertin, 2004a, b), clonidine (Barbeau and Rossignol, 1991; Chau et al, 1998; Cote et al, 2003), L-DOPA (Barbeau and Rossignol, 1991; Guertin, 2004b; De Mello et al, 2004; Doyle and Roberts, 2004; McEwen and Stehouwer, 2001), strychnine (De Leon et al, 1999b; Edgerton et al, 1997a, b), and/or bicuculline (Edgerton et al, 1997a, b; Robinson and Goldberger, 1986) have been shown to facilitate locomotor recovery. The enhanced synaptic transmission generated by using these drugs potentiates other treatments, including spinal cord stimulation and locomotor training, by lowering the activation threshold of the neurons associated with locomotion.…”

Section: Treatment Paradigms For Restoring Locomotor Control After a mentioning

confidence: 99%

Recovery of control of posture and locomotion after a spinal cord injury: solutions staring us in the face

Fong

Roy

Ichiyama

et al. 2009

Progress in Brain Research

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Over the past 20 years, tremendous advances have been made in the field of spinal cord injury research. Yet, consumed with individual pieces of the puzzle, we have failed as a community to grasp the magnitude of the sum of our findings. Our current knowledge should allow us to improve the lives of patients suffering from spinal cord injury. Advances in multiple areas have provided tools for pursuing effective combination of strategies for recovering stepping and standing after a severe spinal cord injury. Muscle physiology research has provided insight into how to maintain functional muscle properties after a spinal cord injury.Understanding the role of the spinal networks in processing sensory information that is important for the generation of motor functions has focused research on developing treatments that sharpen the sensitivity of the locomotor circuitry and that carefully manage the presentation of proprioceptive and cutaneous stimuli to favor recovery. Pharmacological facilitation or inhibition of neurotransmitter systems, spinal cord stimulation, and rehabilitative motor training, which all function by modulating the physiological state of the spinal circuitry, have emerged as promising approaches. Early technological developments, such as robotic training systems and high-density electrode arrays for stimulating the spinal cord, can significantly enhance the precision and minimize the invasiveness of treatment after an injury.Strategies that seek out the complementary effects of combination treatments and that efficiently integrate relevant technical advances in bioengineering represent an untapped potential and are likely to have an immediate impact. Herein, we review key findings in each of these areas of research and present a unified vision for moving forward. Much work remains, but we already have the capability, and more importantly, the responsibility, to help spinal cord injury patients now. Keywordsspinal cord injury; rehabilitation; robotic motor training; pharmacological intervention; skeletal muscle adaptation; proprioception; epidural stimulation; locomotion Why does spinal cord injury result in a loss of movement control?Movements are defined by the combination of motor pools activated, the level at which they are recruited, and the effectiveness with which the corresponding muscles generate force. The diminished level of movement that follows a spinal cord injury has been attributed generally to an inability to activate motor pools. For most individuals with a spinal cord injury, however, this is less of a factor than typically assumed. Three more salient issues are linked to the impaired ability to recruit appropriate ensembles of motor units in a manner that yields effective movement. First, a significant portion of movement loss is attributable to functional alterations of the spinal circuitry that disrupt the coordination of the motor pools. Second, when a person with a severe, incomplete spinal cord lesion attempts to perform a movement, the level of recruitment is insuffi...

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Functional recovery and axonal growth following spinal cord transection is accelerated by sustained l‐DOPA administration

Cited by 12 publications

References 41 publications

Differential effects of l‐DOPA on monoamine metabolism, cell survival and glutathione production in midbrain neuronal‐enriched cultures from parkin knockout and wild‐type mice

Differential effects of l‐DOPA on monoamine metabolism, cell survival and glutathione production in midbrain neuronal‐enriched cultures from parkin knockout and wild‐type mice

Dopaminergic systems in the European eel: characterization, brain distribution, and potential role in migration and reproduction

Recovery of control of posture and locomotion after a spinal cord injury: solutions staring us in the face

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