Decreased striatal dopamine transporter density in JNCL patients with parkinsonian symptoms

Åberg, L.; Liewendahl, K.; Nikkinen, Päivi; Autti, Taina; Rinne, Juha O.; Santavuori, Pirkko

doi:10.1212/wnl.54.5.1069

Cited by 52 publications

(37 citation statements)

References 20 publications

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“…To our knowledge, this is the first report showing quantitatively the amount of the mean gray matter loss be as high as 2.4% per year in JNCL patients during the adolescence, the time period when the clinical symptoms progresses fast [22]. The Cln3 mice model, in contrast to our JNCL patients, have not shown any brain volume loss in their adolescence or middle age [7].…”

Section: Discussionmentioning

confidence: 43%

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JNCL patients show marked brain volume alterations on longitudinal MRI in adolescence

et al. 2008

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Section: Discussionmentioning

confidence: 43%

“…One male patient was compound heterozygotes for the major mutation. All patients received antioxidants and epileptic drug treatment [22]. All patients were blind, had mental decline, epilepsy and parkinsonian symptoms, at least at the time of the last MRI examination.…”

Section: Methodsmentioning

confidence: 99%

JNCL patients show marked brain volume alterations on longitudinal MRI in adolescence

et al. 2008

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“…Psychotic, affective, and schizophreniform features are managed with citalopram, risperidone, olanzapine, or quetiapine. 9 Reports of decreased D1 dopamine transporter density in JNCL by PET, 1, 80 along with similar findings in one of the Cln3 −/− mouse models, 95 suggest that JNCL patients may have a dysregulation of the dopamine system, offering a rationale for a trial of dopaminergic medications. 3 …”

Section: Treatmentmentioning

confidence: 90%

“…1, 2, 3, 83 Regardless of the specific anticonvulsant used, many JNCL patients’ seizures are well controlled.…”

Section: Treatmentmentioning

confidence: 99%

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) and the Eye

Bozorg

Ramirez-Montealegre

Chung

et al. 2009

Survey of Ophthalmology

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Juvenile neuronal ceroid lipofuscinoses (JNCL) or Batten disease is the most common type of NCL in the United States and Europe. This devastating disorder presents with vision failure and progresses to include seizures, motor dysfunction, and dementia. Death usually occurs in the third decade, but some patients die before age twenty. Though the mechanism of visual failure remains poorly understood, recent advances in molecular genetics have improved diagnostic testing and suggested possible therapeutic strategies. The ophthalmologist plays a crucial role in both early diagnosis and documentation of progression of JNCL. We update Batten disease research, particularly as it relates to the eye, and present various theories on the pathophysiology of retinal degeneration.

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“…Imaging studies in JNCL patients have shown dysfunction in the striatum as measured by a reduction in dopamine transporter (DAT) levels and [ 18 F] fluorodopa uptake, an analog of dopamine (Ruottinen et al, 1997;Aberg et al, 2000). Once released into the synaptic cleft, dopamine activates either the D1 or D2 class of receptors.…”

Section: Introductionmentioning

confidence: 99%

Alterations in striatal dopamine catabolism precede loss of substantia nigra neurons in a mouse model of juvenile neuronal ceroid lipofuscinosis

et al. 2007

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Batten disease, or juvenile neuronal ceroid lipofuscinosis (JNCL), results from mutations in the CLN3 gene. This disorder presents clinically around the age of five years with visual deficits progressing to include seizures, cognitive impairment, motor deterioration, hallucinations, and premature death by the third to forth decade of life. The motor deficits include coordination and gait abnormalities, myoclonic jerks, inability to initiate movements, and spasticity. Previous work from our laboratory has identified an early reduction in catechol-O-methyltransferase (COMT), an enzyme responsible for the efficient degradation of dopamine. Alterations in the kinetics of dopamine metabolism could cause the accumulation of undegraded or unsequestered dopamine leading to the formation of toxic dopamine intermediates. We report an imbalance in the catabolism of dopamine in three month Cln3 -/-mice persisting through nine months of age that may be causal to oxidative damage within the striatum at nine months of age. Combined with the Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript previously reported inflammatory changes and loss of post-synaptic D1α receptors, this could facilitate cell loss in striatal projection regions and underlie a general locomotion deficit that becomes apparent at twelve months of age in Cln3 -/-mice. This study provides evidence for early changes in the kinetics of COMT in the Cln3 -/-mouse striatum, affecting the turnover of dopamine, likely leading to neuron loss and motor deficits. These data provide novel insights into the basis of motor deficits in JNCL and how alterations in dopamine catabolism may result in oxidative damage and localized neuronal loss in this disorder.

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Decreased striatal dopamine transporter density in JNCL patients with parkinsonian symptoms

Abstract: The observed decrease in the striatal dopamine transporter density in JNCL offers a rational basis for a trial of dopaminergic drugs in this disease.

Cited by 52 publications

References 20 publications

JNCL patients show marked brain volume alterations on longitudinal MRI in adolescence

JNCL patients show marked brain volume alterations on longitudinal MRI in adolescence

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) and the Eye

Alterations in striatal dopamine catabolism precede loss of substantia nigra neurons in a mouse model of juvenile neuronal ceroid lipofuscinosis

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