Increased vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) expression in adolescent brain development

A longitudinal micro-PET/CT study in rodent

Donglang Jiang, Xiuhong Lu, Zijing Li, Nicklas Rydberg, Chuantao Zuo, Fangyu Peng, Fengchun Hua, Yihui Guan, Fang Xie

Research output: Contribution to journalArticle

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Abstract

Background: Brain development and maturation in adolescence is a complex process with active changes of metabolic and neurotransmission pathways. Positron emission tomography (PET) is a useful imaging modality for tracking metabolic and functional changes in adolescent brain. In this study, changes of glucose metabolism, expression of vesicular monoamine transporter 2 and dopamine transporter during adolescent brain development in rats were investigated with PET/CT. Methods: A longitudinal PET/CT study of age-dependent changes of VMAT2, DAT and glucose metabolism in adolescent brain was conducted in a group of Wistar rats (n = 6) post sequential intravenous injection of 18 F-PF-(+)-DTBZ, 11 C-CFT, and 18 F-FDG, respectively. PET acquisition was performed at 2, 4, 9, and 12 months of age. Radiotracer uptake in different brain regions, including the striatum, cerebellum, and hippocampus, were quantified and recorded as Standardized uptake value (SUV) and striatal specific uptake ratio (SUVR: SUV in brain regions/SUV in cerebellum). Results: Variable uptake of 18 F-PF-(+)-DTBZ and 11 C-CFT were detected, with highest level uptake in the striatum and accumbens. There was significant age-dependent increase of 18 F-PF-(+)-DTBZ and 11 C-CFT uptake in the striatum from 2 months of age (SUV: 1.36 ± 0.22, 1.37 ± 0.39, respectively), to 4 months (SUV: 2.22 ± 0.29, 2.04 ± 0.33), 9 months (1.98 ± 0.34, 2.09 ± 0.18), 12 months (SUV: 1.93 ± 0.19, 2.00 ± 0.17) of age, SUV of 18 F-FDG also increased from 2 months of age to older ages (SUV in the striatum: 3.71 ± 0.78 at 2 month, 5.28 ± 0.81, 5.14 ± 0.73, 4.94 ± 0.50 at 4, 9, 12 month, respectively). Conclusion: Age-dependent increases of striatal of 18 F-FDG, 18 F-PF-(+)-DTBZ, and 11 C-CFT uptake were detected in rats from 2 to 4 month of age, demonstrating striatal development presents over the first 4 months of age. Four months of age can be considered a safe threshold to launch brain disease studies for exclusion of confusion of continuing tissue development. These findings support further investigation of age-dependent changes in expression of DAT, VMAT2, and glucose metabolism for their potential use as a new imaging biomarker for study of brain development and functional maturation.

Original languageEnglish (US)
Article number1052
JournalFrontiers in Neuroscience
Volume12
DOIs
StatePublished - Jan 1 2019

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Vesicular Monoamine Transport Proteins
Adolescent Development
Dopamine Plasma Membrane Transport Proteins
Positron-Emission Tomography
Rodentia
Corpus Striatum
Brain
Glucose
Cerebellum
Brain Diseases
Metabolic Networks and Pathways
Intravenous Injections
Synaptic Transmission
Wistar Rats
Hippocampus
Biomarkers
pseudoginsenoside F11

Keywords

  • Brain development
  • Dopamine transporter (DAT)
  • Glucose metabolism
  • Positron emission tomography
  • Vesicular monoamine transporter 2 (VMAT2)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Increased vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) expression in adolescent brain development : A longitudinal micro-PET/CT study in rodent. / Jiang, Donglang; Lu, Xiuhong; Li, Zijing; Rydberg, Nicklas; Zuo, Chuantao; Peng, Fangyu; Hua, Fengchun; Guan, Yihui; Xie, Fang.

In: Frontiers in Neuroscience, Vol. 12, 1052, 01.01.2019.

Research output: Contribution to journalArticle

Jiang, Donglang ; Lu, Xiuhong ; Li, Zijing ; Rydberg, Nicklas ; Zuo, Chuantao ; Peng, Fangyu ; Hua, Fengchun ; Guan, Yihui ; Xie, Fang. / Increased vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) expression in adolescent brain development : A longitudinal micro-PET/CT study in rodent. In: Frontiers in Neuroscience. 2019 ; Vol. 12.
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abstract = "Background: Brain development and maturation in adolescence is a complex process with active changes of metabolic and neurotransmission pathways. Positron emission tomography (PET) is a useful imaging modality for tracking metabolic and functional changes in adolescent brain. In this study, changes of glucose metabolism, expression of vesicular monoamine transporter 2 and dopamine transporter during adolescent brain development in rats were investigated with PET/CT. Methods: A longitudinal PET/CT study of age-dependent changes of VMAT2, DAT and glucose metabolism in adolescent brain was conducted in a group of Wistar rats (n = 6) post sequential intravenous injection of 18 F-PF-(+)-DTBZ, 11 C-CFT, and 18 F-FDG, respectively. PET acquisition was performed at 2, 4, 9, and 12 months of age. Radiotracer uptake in different brain regions, including the striatum, cerebellum, and hippocampus, were quantified and recorded as Standardized uptake value (SUV) and striatal specific uptake ratio (SUVR: SUV in brain regions/SUV in cerebellum). Results: Variable uptake of 18 F-PF-(+)-DTBZ and 11 C-CFT were detected, with highest level uptake in the striatum and accumbens. There was significant age-dependent increase of 18 F-PF-(+)-DTBZ and 11 C-CFT uptake in the striatum from 2 months of age (SUV: 1.36 ± 0.22, 1.37 ± 0.39, respectively), to 4 months (SUV: 2.22 ± 0.29, 2.04 ± 0.33), 9 months (1.98 ± 0.34, 2.09 ± 0.18), 12 months (SUV: 1.93 ± 0.19, 2.00 ± 0.17) of age, SUV of 18 F-FDG also increased from 2 months of age to older ages (SUV in the striatum: 3.71 ± 0.78 at 2 month, 5.28 ± 0.81, 5.14 ± 0.73, 4.94 ± 0.50 at 4, 9, 12 month, respectively). Conclusion: Age-dependent increases of striatal of 18 F-FDG, 18 F-PF-(+)-DTBZ, and 11 C-CFT uptake were detected in rats from 2 to 4 month of age, demonstrating striatal development presents over the first 4 months of age. Four months of age can be considered a safe threshold to launch brain disease studies for exclusion of confusion of continuing tissue development. These findings support further investigation of age-dependent changes in expression of DAT, VMAT2, and glucose metabolism for their potential use as a new imaging biomarker for study of brain development and functional maturation.",
keywords = "Brain development, Dopamine transporter (DAT), Glucose metabolism, Positron emission tomography, Vesicular monoamine transporter 2 (VMAT2)",
author = "Donglang Jiang and Xiuhong Lu and Zijing Li and Nicklas Rydberg and Chuantao Zuo and Fangyu Peng and Fengchun Hua and Yihui Guan and Fang Xie",
year = "2019",
month = "1",
day = "1",
doi = "10.3389/fnins.2018.01052",
language = "English (US)",
volume = "12",
journal = "Frontiers in Neuroscience",
issn = "1662-4548",
publisher = "Frontiers Research Foundation",

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TY - JOUR

T1 - Increased vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) expression in adolescent brain development

T2 - A longitudinal micro-PET/CT study in rodent

AU - Jiang, Donglang

AU - Lu, Xiuhong

AU - Li, Zijing

AU - Rydberg, Nicklas

AU - Zuo, Chuantao

AU - Peng, Fangyu

AU - Hua, Fengchun

AU - Guan, Yihui

AU - Xie, Fang

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Brain development and maturation in adolescence is a complex process with active changes of metabolic and neurotransmission pathways. Positron emission tomography (PET) is a useful imaging modality for tracking metabolic and functional changes in adolescent brain. In this study, changes of glucose metabolism, expression of vesicular monoamine transporter 2 and dopamine transporter during adolescent brain development in rats were investigated with PET/CT. Methods: A longitudinal PET/CT study of age-dependent changes of VMAT2, DAT and glucose metabolism in adolescent brain was conducted in a group of Wistar rats (n = 6) post sequential intravenous injection of 18 F-PF-(+)-DTBZ, 11 C-CFT, and 18 F-FDG, respectively. PET acquisition was performed at 2, 4, 9, and 12 months of age. Radiotracer uptake in different brain regions, including the striatum, cerebellum, and hippocampus, were quantified and recorded as Standardized uptake value (SUV) and striatal specific uptake ratio (SUVR: SUV in brain regions/SUV in cerebellum). Results: Variable uptake of 18 F-PF-(+)-DTBZ and 11 C-CFT were detected, with highest level uptake in the striatum and accumbens. There was significant age-dependent increase of 18 F-PF-(+)-DTBZ and 11 C-CFT uptake in the striatum from 2 months of age (SUV: 1.36 ± 0.22, 1.37 ± 0.39, respectively), to 4 months (SUV: 2.22 ± 0.29, 2.04 ± 0.33), 9 months (1.98 ± 0.34, 2.09 ± 0.18), 12 months (SUV: 1.93 ± 0.19, 2.00 ± 0.17) of age, SUV of 18 F-FDG also increased from 2 months of age to older ages (SUV in the striatum: 3.71 ± 0.78 at 2 month, 5.28 ± 0.81, 5.14 ± 0.73, 4.94 ± 0.50 at 4, 9, 12 month, respectively). Conclusion: Age-dependent increases of striatal of 18 F-FDG, 18 F-PF-(+)-DTBZ, and 11 C-CFT uptake were detected in rats from 2 to 4 month of age, demonstrating striatal development presents over the first 4 months of age. Four months of age can be considered a safe threshold to launch brain disease studies for exclusion of confusion of continuing tissue development. These findings support further investigation of age-dependent changes in expression of DAT, VMAT2, and glucose metabolism for their potential use as a new imaging biomarker for study of brain development and functional maturation.

AB - Background: Brain development and maturation in adolescence is a complex process with active changes of metabolic and neurotransmission pathways. Positron emission tomography (PET) is a useful imaging modality for tracking metabolic and functional changes in adolescent brain. In this study, changes of glucose metabolism, expression of vesicular monoamine transporter 2 and dopamine transporter during adolescent brain development in rats were investigated with PET/CT. Methods: A longitudinal PET/CT study of age-dependent changes of VMAT2, DAT and glucose metabolism in adolescent brain was conducted in a group of Wistar rats (n = 6) post sequential intravenous injection of 18 F-PF-(+)-DTBZ, 11 C-CFT, and 18 F-FDG, respectively. PET acquisition was performed at 2, 4, 9, and 12 months of age. Radiotracer uptake in different brain regions, including the striatum, cerebellum, and hippocampus, were quantified and recorded as Standardized uptake value (SUV) and striatal specific uptake ratio (SUVR: SUV in brain regions/SUV in cerebellum). Results: Variable uptake of 18 F-PF-(+)-DTBZ and 11 C-CFT were detected, with highest level uptake in the striatum and accumbens. There was significant age-dependent increase of 18 F-PF-(+)-DTBZ and 11 C-CFT uptake in the striatum from 2 months of age (SUV: 1.36 ± 0.22, 1.37 ± 0.39, respectively), to 4 months (SUV: 2.22 ± 0.29, 2.04 ± 0.33), 9 months (1.98 ± 0.34, 2.09 ± 0.18), 12 months (SUV: 1.93 ± 0.19, 2.00 ± 0.17) of age, SUV of 18 F-FDG also increased from 2 months of age to older ages (SUV in the striatum: 3.71 ± 0.78 at 2 month, 5.28 ± 0.81, 5.14 ± 0.73, 4.94 ± 0.50 at 4, 9, 12 month, respectively). Conclusion: Age-dependent increases of striatal of 18 F-FDG, 18 F-PF-(+)-DTBZ, and 11 C-CFT uptake were detected in rats from 2 to 4 month of age, demonstrating striatal development presents over the first 4 months of age. Four months of age can be considered a safe threshold to launch brain disease studies for exclusion of confusion of continuing tissue development. These findings support further investigation of age-dependent changes in expression of DAT, VMAT2, and glucose metabolism for their potential use as a new imaging biomarker for study of brain development and functional maturation.

KW - Brain development

KW - Dopamine transporter (DAT)

KW - Glucose metabolism

KW - Positron emission tomography

KW - Vesicular monoamine transporter 2 (VMAT2)

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U2 - 10.3389/fnins.2018.01052

DO - 10.3389/fnins.2018.01052

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JO - Frontiers in Neuroscience

JF - Frontiers in Neuroscience

SN - 1662-4548

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