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Imaging Intracellular Ca2+ Signals in Striatal Astrocytes from Adult Mice Using Genetically-encoded Calcium Indicators
Published on: November 19, 2014
Dopamine-Induced L-Lactate Production in Cortical Astrocytes Cross-Reacts with β1-Adrenoceptor-Mediated cAMP
Keita Sugiyama1,2, Anemari Horvat1,3, Klemen Dolinar4
1Laboratory of Neuroendocrinology - Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Dopamine (DA) stimulates astrocytes to produce lactate, a key energy source for neurons. This process involves cyclic adenosine monophosphate (cAMP) signaling and beta-1 adrenoceptors, revealing a new pathway relevant to neurodegenerative diseases.
Area of Science:
- Neuroscience
- Cellular Biology
- Biochemistry
Background:
- Astrocytes are crucial for central nervous system homeostasis and neuronal function.
- Noradrenaline (NA) stimulates astrocyte glycolysis and lactate production via cAMP signaling.
- Degeneration of noradrenergic neurons in diseases like Parkinson's may impair astrocyte function.
Purpose of the Study:
- To investigate dopamine's (DA) effect on astrocyte cyclic adenosine monophosphate (cAMP) signaling and L-lactate production.
- To determine the role of specific receptors and signaling pathways in DA-mediated astrocytic responses.
- To explore potential DA-based modulation of astrocyte metabolism.
Main Methods:
- Utilized fluorescence resonance energy transfer (FRET)-based nanosensor imaging in cultured rat cortical astrocytes.
- Measured DA-induced changes in cytosolic cAMP levels and L-lactate production.
- Employed super-resolution stimulated emission depletion (STED) microscopy to assess receptor colocalization and performed receptor knockdown experiments (Adrb1).
Main Results:
- DA dose-dependently increased astrocyte cytosolic cAMP with an EC50 of 1.25 μM.
- DA stimulated a delayed L-lactate production dependent on cAMP signaling.
- Knockdown of beta-1 adrenoceptors (Adrb1) significantly attenuated DA-induced cAMP and lactate production, despite minimal D1-beta-1 receptor colocalization.
Conclusions:
- Identified a novel dopaminergic pathway regulating astrocytic glycolytic activation.
- Demonstrated that DA modulates astrocyte metabolism via cAMP signaling, involving beta-1 adrenoceptors.
- Findings suggest potential dysregulation of this pathway in neurodegenerative conditions.
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