Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice

Abstract Dopamine (DA) plays a vital role in brain physiology and pathology such as learning and memory, motor control, neurological diseases, and psychiatric diseases. In neurons, it has been well established that DA increases or decreases intracellular cyclic AMP (cAMP) through D1-like or D2-like...

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Main Authors: Sunpil Kim, Jea Kwon, Mingu Gordon Park, C. Justin Lee
Format: Article
Language:English
Published: BMC 2022-11-01
Series:Molecular Brain
Subjects:
Online Access:https://doi.org/10.1186/s13041-022-00977-w
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author Sunpil Kim
Jea Kwon
Mingu Gordon Park
C. Justin Lee
author_facet Sunpil Kim
Jea Kwon
Mingu Gordon Park
C. Justin Lee
author_sort Sunpil Kim
collection DOAJ
description Abstract Dopamine (DA) plays a vital role in brain physiology and pathology such as learning and memory, motor control, neurological diseases, and psychiatric diseases. In neurons, it has been well established that DA increases or decreases intracellular cyclic AMP (cAMP) through D1-like or D2-like dopamine receptors, respectively. In contrast, it has been elusive how astrocytes respond to DA via Ca2+ signaling and regulate synaptic transmission and reward systems. Previous studies suggest various molecular targets such as MAO-B, D1R, or D1R–D2R heteromer to modulate astrocytic Ca2+ signaling. However, which molecular target is utilized under what physiological condition remains unclear. Here, we show that DA-induced astrocytic Ca2+ signaling pathway switches during development: MAO-B is the major player at a young age (5–6 weeks), whereas DA receptors (DARs) are responsible for the adult period (8–12 weeks). DA-mediated Ca2+ response in the adult period was decreased by either D1R or D2R blockers, which are primarily known for cyclic AMP signaling (Gs and Gi pathway, respectively), suggesting that this Ca2+ response might be mediated through Gq pathway by D1R–D2R heterodimer. Moreover, DAR-mediated Ca2+ response was not blocked by TTX, implying that this response is not a secondary response caused by neuronal activation. Our study proposes an age-specific molecular target of DA-induced astrocytic Ca2+ signaling: MAO-B in young mice and DAR in adult mice.
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spelling doaj.art-1f470a1515434398998b8561d7d233082022-12-22T02:46:23ZengBMCMolecular Brain1756-66062022-11-011511710.1186/s13041-022-00977-wDopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult miceSunpil Kim0Jea Kwon1Mingu Gordon Park2C. Justin Lee3KU-KIST Graduate School of Converging Science and Technology, Korea UniversityCenter for Cognition and Sociality, Cognitive Glioscience Group, Institute for Basic Science (IBS)KU-KIST Graduate School of Converging Science and Technology, Korea UniversityKU-KIST Graduate School of Converging Science and Technology, Korea UniversityAbstract Dopamine (DA) plays a vital role in brain physiology and pathology such as learning and memory, motor control, neurological diseases, and psychiatric diseases. In neurons, it has been well established that DA increases or decreases intracellular cyclic AMP (cAMP) through D1-like or D2-like dopamine receptors, respectively. In contrast, it has been elusive how astrocytes respond to DA via Ca2+ signaling and regulate synaptic transmission and reward systems. Previous studies suggest various molecular targets such as MAO-B, D1R, or D1R–D2R heteromer to modulate astrocytic Ca2+ signaling. However, which molecular target is utilized under what physiological condition remains unclear. Here, we show that DA-induced astrocytic Ca2+ signaling pathway switches during development: MAO-B is the major player at a young age (5–6 weeks), whereas DA receptors (DARs) are responsible for the adult period (8–12 weeks). DA-mediated Ca2+ response in the adult period was decreased by either D1R or D2R blockers, which are primarily known for cyclic AMP signaling (Gs and Gi pathway, respectively), suggesting that this Ca2+ response might be mediated through Gq pathway by D1R–D2R heterodimer. Moreover, DAR-mediated Ca2+ response was not blocked by TTX, implying that this response is not a secondary response caused by neuronal activation. Our study proposes an age-specific molecular target of DA-induced astrocytic Ca2+ signaling: MAO-B in young mice and DAR in adult mice.https://doi.org/10.1186/s13041-022-00977-wDopamineAstrocyteCa2+ responseMAO-BDopamine receptorsDevelopment
spellingShingle Sunpil Kim
Jea Kwon
Mingu Gordon Park
C. Justin Lee
Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice
Molecular Brain
Dopamine
Astrocyte
Ca2+ response
MAO-B
Dopamine receptors
Development
title Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice
title_full Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice
title_fullStr Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice
title_full_unstemmed Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice
title_short Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice
title_sort dopamine induced astrocytic ca2 signaling in mpfc is mediated by mao b in young mice but by dopamine receptors in adult mice
topic Dopamine
Astrocyte
Ca2+ response
MAO-B
Dopamine receptors
Development
url https://doi.org/10.1186/s13041-022-00977-w
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AT mingugordonpark dopamineinducedastrocyticca2signalinginmpfcismediatedbymaobinyoungmicebutbydopaminereceptorsinadultmice
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