Perturbed Development of Striatal Dopamine Transporters in Fatty Versus Lean Zucker Rats: a Follow-up Small Animal PET Study

Cumming, Paul; Maschauer, Simone; Riss, Patrick J.; Grill, Eva; Pischetsrieder, Monika; Kuwert, Torsten; Prante, Olaf

doi:10.1007/s11307-014-0811-7

Cited by 9 publications

(5 citation statements)

References 44 publications

(58 reference statements)

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“…We also measured the DAT density availability at baseline and on day 14 of HAL treatment (follow-up). Pairs of BP ND maps were calculated relative to the cerebellum TAC, as documented in our previous characterization of this DAT ligand [20,23].…”

Section: Micropet Brain Studymentioning

confidence: 99%

A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter

et al. 2018

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Antipsychotic drugs are effective interventions in schizophrenia. However, the efficacy of these agents often decreases over time, which leads to treatment failure and symptom recurrence. We report that antipsychotic efficacy in rat models declines in concert with extracellular striatal dopamine levels rather than insufficient dopamine D2 receptor occupancy. Antipsychotic efficacy was associated with a suppression of dopamine transporter activity, which was reversed during failure. Antipsychotic failure coincided with reduced dopamine neuron firing, which was not observed during antipsychotic efficacy. Synaptic field responses in dopamine target areas declined during antipsychotic efficacy and showed potentiation during failure. Antipsychotics blocked synaptic vesicle release during efficacy but enhanced this release during failure. We found that the pharmacological inhibition of the dopamine transporter rescued antipsychotic drug treatment outcomes, supporting the hypothesis that the dopamine transporter is a main target of antipsychotic drugs and predicting that dopamine transporter blockers may be an adjunct treatment to reverse antipsychotic treatment failure.

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Section: Micropet Brain Studymentioning

confidence: 99%

A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter

et al. 2018

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“…Comparisons of rats using PET or single-photon emission computerized tomography have also shown reduced DAT density in older rats [24,25]. However, in a study using DAT PET, Cumming et al showed that the binding potential in the striatum of Zucker rats was higher at 6 months of age than at 6 weeks of age [26]. This conflicting result suggests that the binding potential at 6 weeks of age was a greater influence than age-related decline in DAT expression at 6 months of age.…”

Section: Discussionmentioning

confidence: 99%

Effects of Maturation on Striatal Dopamine Transporter Availability in Rats

et al. 2019

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Objectives We investigated the effects of maturation on dopamine transporter (DAT) availability in the rat via longitudinal monitoring with positron emission tomography (PET). Methods Eight 5-week-old male Sprague-Dawley rats (113–186 g) were used. Four 18F-FP-CIT PET scans were taken at 5, 10, 15, and 20 weeks. Baseline PET images were manually fused with the built-in magnetic resonance imaging template; volumes of interest (VOIs) were manually defined by placing a spherical region around the hot spot with the maximum count rate. VOIs were placed on bilateral caudate and putamen (CPu), nucleus accumbens (NAc), and cerebellum. Specific binding ratios (SBRs) were calculated as follows: (mean uptake of bilateral targets – mean uptake of bilateral cerebellum)/(mean uptake of bilateral cerebellum). Results In CPu, SBRs at 5 weeks (3.25 ± 0.66) were lower than those at 10 weeks (4.59 ± 0.78, p = 0.1151) and at 15 weeks (5.56 ± 0.92, p = 0.0182). In NAc, SBRs at 5 weeks (1.41 ± 0.47) were lower than those at 10 weeks (2.03 ± 0.36, p = 0.1960) and at 15 weeks (2.43 ± 0.50, p = 0.0427). SBRs in CPu and NAc significantly increased with maturation until 15 weeks. However, differences in SBR between 15 and 20 weeks were not significant. Conclusions Striatal DAT availability increases until 15 weeks postnatally, then remains stable, reflecting maturation of the dopaminergic system in rats.

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“…Thus far, few imaging studies have been reported on alterations in the central nervous system of T2DM models, including [ 18 F]FP-CMT for dopamine innervation[44] and [ 18 F]FDG for metabolism. Cognitive impairment, cortical thinning, and hippocampal synaptic reorganization have been observed in T2DM rats [6].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reduced SV2A and GABA_Areceptor levels in the brains of type 2 diabetic rats revealed by [¹⁸F]SDM-8 and [¹⁸F]flumazenil PET

Kong,

Xie,

Wang

et al. 2023

Preprint

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PurposeType 2 diabetes mellitus (T2DM) is associated with a greater risk of Alzheimer’s disease. Synaptic impairment and protein aggregates have been reported in the brains of T2DM models. Here, we assessed whether neurodegenerative changes in synaptic vesicle 2A (SV2A), γ;-aminobutyric acid type A (GABAA) receptor, amyloid-β, tau and receptor for advanced glycosylation end product (RAGE) can be detected in vivo in T2DM rats.MethodsPositron emission tomography (PET) using [18F]SDM-8 (SV2A), [18F]flumazenil (GABAAreceptor), [18F]florbetapir (amyloid-β), [18F]PM-PBB3 (tau), and [18F]FPS-ZM1 (RAGE) was carried out in 12-month-old diabetic Zucker diabetic fatty (ZDF) and Sprague□Dawley (SD) rats. Proteomic profiling and pathway analysis of the hippocampus of ZDF and SD rats were performed.ResultsReduced cortical [18F]SDM-8 and cortical and hippocampal [18F]flumazenil uptake were observed in 12-month-old ZDF rats compared to SD rats. [18F]florbetapir and [18F]PM-PBB3 uptake were comparable in the brains of 12-month-old ZDF rats and SD rats.ConclusionThe findings provide in vivo evidence for regional reductions in SV2A and GABAAreceptor levels in the brains of aged T2DM ZDF rats.

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Perturbed Development of Striatal Dopamine Transporters in Fatty Versus Lean Zucker Rats: a Follow-up Small Animal PET Study

Abstract: Maturation of the striatal dopamine innervation is impaired in this model of obesity/hyperlipidaemia without diabetes, implying an acquired trait of reduced dopamine reuptake capacity.

Cited by 9 publications

References 44 publications

A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter

A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter

Effects of Maturation on Striatal Dopamine Transporter Availability in Rats

Reduced SV2A and GABA_Areceptor levels in the brains of type 2 diabetic rats revealed by [¹⁸F]SDM-8 and [¹⁸F]flumazenil PET

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Perturbed Development of Striatal Dopamine Transporters in Fatty Versus Lean Zucker Rats: a Follow-up Small Animal PET Study

Abstract: Maturation of the striatal dopamine innervation is impaired in this model of obesity/hyperlipidaemia without diabetes, implying an acquired trait of reduced dopamine reuptake capacity.

Cited by 9 publications

References 44 publications

A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter

A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter

Effects of Maturation on Striatal Dopamine Transporter Availability in Rats

Reduced SV2A and GABAAreceptor levels in the brains of type 2 diabetic rats revealed by [18F]SDM-8 and [18F]flumazenil PET

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Product

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Reduced SV2A and GABA_Areceptor levels in the brains of type 2 diabetic rats revealed by [¹⁸F]SDM-8 and [¹⁸F]flumazenil PET