Age-related decline in dopamine transporter in human brain using PET with a new radioligand [18F]FE-PE2I

Shingai, Yoshitoshi; Tateno, Amane; Arakawa, Ryosuke; Sakayori, Takeshi; Kim, Woochan; Suzuki, Hidenori; Okubo, Yoshiro

doi:10.1007/s12149-013-0798-1

Cited by 28 publications

(37 citation statements)

References 40 publications

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“…Imaging studies have revealed gradual and region-specific reductions in DAT density with age (Shingai et al, 2014; Volkow et al, 1998, 1996), supporting post-mortem findings of significant loss of nigrostriatal DA neurons even in the absence of neurodegenerative disease (Fearnley and Lees, 1991). Additionally, several major age-dependent disorders are known to be associated with DAT polymorphisms, such as Alzheimer’s disease (Lin et al, 2012) and Parkinson’s disease (le Couteur et al, 1997; Ritz et al, 2009).…”

Section: Introductionmentioning

confidence: 54%

Dopaminergic control of anxiety in young and aged zebrafish

Kacprzak

Patel

Riley

et al. 2017

Pharmacology Biochemistry and Behavior

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Changes in the expression of the dopamine transporter (DAT), or the sensitivity of dopamine receptors, are associated with aging and substance abuse and may underlie some of the symptoms common to both conditions. In this study, we explored the role of the dopaminergic system in the anxiogenic effects of aging and acute cocaine exposure by comparing the behavioral phenotypes of wildtype (WT) and DAT knockout zebrafish (DAT-KO) of different ages. To determine the involvement of specific dopamine receptors in anxiety states, antagonists to D1 (SCH23390) and D2/D3 (sulpiride) were employed. We established that DAT-KO results in a chronic anxiety-like state, seen as an increase in bottom-dwelling and thigmotaxis. Similar effects were produced by aging and acute cocaine administration, both leading to reduction in DAT mRNA abundance (qPCR). Inhibition of D1 activity counteracted the anxiety-like effects associated with DAT deficit, independent of its origin. Inhibition of D2/D3 receptors reduced anxiety in young DAT-KO, enhanced the anxiogenic effects of cocaine in WT, but did not affect aged WT or DAT-KO fish. These findings provide new evidence that the dopaminergic system plays a critical role in anxiety-like states, and suggest that adult zebrafish provide a sensitive diurnal vertebrate model for elucidating the molecular mechanisms of anxiety and a platform for anxiolytic drug screens.

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Section: Introductionmentioning

confidence: 54%

Dopaminergic control of anxiety in young and aged zebrafish

Kacprzak

Patel

Riley

et al. 2017

Pharmacology Biochemistry and Behavior

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“…The dopamine transporter (DAT) is a presynaptic protein with a key role in dopamine neurotransmission and is a sensitive marker of the dopaminergic neuronal integrity [10]. Available striatal DAT sites diminish in the course of PD [11], and age is proposed to have a slight and uneven effect on it, as compared to the physiological decline that occurs with aging [12,13]. In vivo imaging of the DAT with SPECT [14] has become available in an increasing number of movement disorders clinics.…”

Section: I-fp-cit Spect Imaging Data Analysismentioning

confidence: 99%

“…Imaging studies in controls propose that there is a physiological decline of the striatal DAT expression that is age-related [26] and that this decline is even for the caudate and the putamen [13]. In PD, studies suggest that striatal DAT availabilities decline to a greater extent than in controls Representative images (on the axial plane) of 123 I-FP-CIT specific to non-specific binding in the striatum of two Parkinson's disease (PD) patients at baseline (upper row) and at follow-up (lower row).…”

Section: S9mentioning

confidence: 99%

Parkinson’s Disease Dyskinesias Possibly Relate to Greater Dopamine Transporter Losses in the Putamen Over Time

Roussakis¹,

Towey²,

Gennaro³

et al. 2019

J Neurol Exp Neurosci

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The pathophysiology of levodopa-induced dyskinesias in Parkinson's disease is incompletely understood. This study was designed to investigate in Parkinson's patients, whether time-related changes in striatal dopamine transporter availability are associated to the appearance of dyskinesias. 15 Parkinson's patients had dopamine transporter-specific SPECT imaging with 123 I-FP-CIT twice: at baseline (when they were drug naïve) and at follow-up (6.31 ± 2.29 years from baseline), and were followed up clinically every six months. At the end of the study, patients were divided in two groups according to whether they had developed dyskinesias or not. Semiquantification of 123 I-FP-CIT data was performed using the occipital cortex as the reference region. Specific binding ratios were calculated for the putamen and the caudate. During the clinical follow-up, all Parkinson's patients were treated pharmaceutically. 8 patients developed dyskinesias, while 7 remained nondyskinetic. At baseline, the two groups had similar 123 I-FP-CIT specific binding ratio values for the putamen and the caudate (p > 0.05). Also, between-group differences in age, disease duration, and Hoehn & Yahr scores were not statistically significant. Overtime, the putaminal 123 I-FP-CIT specific binding ratio values in the dyskinetic group decreased significantly (p < 0.01). The nondyskinetic patients had smaller reductions (p < 0.05) during the same period of time. At follow-up, the dyskinetic patients had significantly higher Hoehn & Yahr scores (p < 0.01) and were taking higher levodopa equivalent doses (p < 0.001), as compared to the nondyskinetic patients. The development of Parkinson's dyskinesias is related to a faster progression rate, as reflected by marked putaminal dopamine transporter decreases.

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“…12,13 The overdosing effect of dopaminergic drugs may be more severe in patients with younger PD onset, considering that dopaminergic function physiologically declines with aging. 14 Dopaminergic drugs interfere with phasic processing of rewards provided by ventral striatum dopamine neurons, strengthening dopaminergic peaks (associated with unexpected rewards), and preventing dopaminergic dips (associated with failures of expected rewards), as confirmed by impairments in reward learning induced by dopaminergic therapy in the early stages of PD; 15,16 this effect is stronger for the tonic stimulation provided by dopamine agonists in comparison with the phasic stimulation provided by levodopa. 17,18 The alteration of reward learning (strengthened dopaminergic peaks associated with rewards, prevented dopaminergic dips associated with failures of expected rewards) induced especially by dopamine agonists represents the pathophysiological basis 19,20 of behavioral addictions in PD patients.…”

Section: Introductionmentioning

confidence: 99%

The dark side of dopaminergic therapies in Parkinson’s disease: shedding light on aberrant salience

Poletti

2017

CNS Spectr.

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Psychotic subjects and patients with Parkinson's disease (PD) "on" dopaminergic drugs, especially on dopamine agonists, present a hyperdopaminergic state that interferes with learning processing. These clinical populations present with distinct alterations of learning that share an increased potential motivational significance of stimuli: psychotic subjects may attribute salience to neutral stimuli, while medicated PD patients may overvalue rewards. Herein is discussed the speculative hypothesis that the hyperdopaminergic state induced by dopaminergic treatments, especially with dopamine agonists, may also facilitate the attribution of salience to neutral stimuli in PD patients, altering the physiological attribution of salience. Preliminary empirical evidence is in agreement with this speculative hypothesis, which needs further empirical investigation. The clinical implications of this hypothesis are discussed in relation to behavioral addictions, psychosis proneness, and enhanced creativity in medicated PD patients.

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Age-related decline in dopamine transporter in human brain using PET with a new radioligand [18F]FE-PE2I

Cited by 28 publications

References 40 publications

Dopaminergic control of anxiety in young and aged zebrafish

Dopaminergic control of anxiety in young and aged zebrafish

Parkinson’s Disease Dyskinesias Possibly Relate to Greater Dopamine Transporter Losses in the Putamen Over Time

The dark side of dopaminergic therapies in Parkinson’s disease: shedding light on aberrant salience

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