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...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2022-11-01
|
Series: | Molecular Brain |
Subjects: | |
Online Access: | https://doi.org/10.1186/s13041-022-00977-w |
_version_ | 1811319570636472320 |
---|---|
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. |
first_indexed | 2024-04-13T12:45:16Z |
format | Article |
id | doaj.art-1f470a1515434398998b8561d7d23308 |
institution | Directory Open Access Journal |
issn | 1756-6606 |
language | English |
last_indexed | 2024-04-13T12:45:16Z |
publishDate | 2022-11-01 |
publisher | BMC |
record_format | Article |
series | Molecular Brain |
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 |
work_keys_str_mv | AT sunpilkim dopamineinducedastrocyticca2signalinginmpfcismediatedbymaobinyoungmicebutbydopaminereceptorsinadultmice AT jeakwon dopamineinducedastrocyticca2signalinginmpfcismediatedbymaobinyoungmicebutbydopaminereceptorsinadultmice AT mingugordonpark dopamineinducedastrocyticca2signalinginmpfcismediatedbymaobinyoungmicebutbydopaminereceptorsinadultmice AT cjustinlee dopamineinducedastrocyticca2signalinginmpfcismediatedbymaobinyoungmicebutbydopaminereceptorsinadultmice |