Astroglial Serotonin Receptors as the Central Target of Classic Antidepressants

Verkhratsky, Alexei; Parpura, Vladimir; Scuderi, Caterina

doi:10.1007/978-3-030-77375-5_13

Cited by 10 publications

(8 citation statements)

References 258 publications

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“…Dysfunctions of the 5-HT system are involved in mood disorders, including depression [ 90 ]. Since astrocytes express transporters and receptors for the sensing of serotonergic transmission [ 91 ], we continued by analyzing the astrocytic Ca 2+ responses induced by 5-HT local stimulation in naïve and Cort-mice in mPFC brain slices. Following a similar viral strategy, AAV5-GFAP-cytoGCaMP6f was selectively expressed in mPFC astrocytes and local Ca 2+ events were monitored in basal conditions and in response to local 5-HT application (1 mM, air puff 10 s, 1 bar) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states

González-Arias,

Sánchez-Ruiz,

Esparza

et al. 2023

Mol Psychiatry

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Astrocytes play crucial roles in brain homeostasis and are regulatory elements of neuronal and synaptic physiology. Astrocytic alterations have been found in Major Depressive Disorder (MDD) patients; however, the consequences of astrocyte Ca2+ signaling in MDD are poorly understood. Here, we found that corticosterone-treated juvenile mice (Cort-mice) showed altered astrocytic Ca2+ dynamics in mPFC both in resting conditions and during social interactions, in line with altered mice behavior. Additionally, Cort-mice displayed reduced serotonin (5-HT)-mediated Ca2+ signaling in mPFC astrocytes, and aberrant 5-HT-driven synaptic plasticity in layer 2/3 mPFC neurons. Downregulation of astrocyte Ca2+ signaling in naïve animals mimicked the synaptic deficits found in Cort-mice. Remarkably, boosting astrocyte Ca2+ signaling with Gq-DREADDS restored to the control levels mood and cognitive abilities in Cort-mice. This study highlights the important role of astrocyte Ca2+ signaling for homeostatic control of brain circuits and behavior, but also reveals its potential therapeutic value for depressive-like states.

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Section: Resultsmentioning

confidence: 99%

Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states

González-Arias,

Sánchez-Ruiz,

Esparza

et al. 2023

Mol Psychiatry

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“…Altered serotonergic-driven astrocytic Ca 2+ responses in depressive-like states Dysfunctions of the 5-HT system are involved in mood disorders, including depression 49 . Since astrocytes express transporters and receptors for the sensing of serotonergic transmission 50 , we continued by analyzing the astrocytic Ca 2+ responses induced by 5-HT local stimulation in naïve and Cort-mice in mPFC brain slices. Following a similar viral strategy, AAV5-Gfap-cytoGCaMP6f was selectively expressed in mPFC astrocytes and local Ca 2+ events were monitored in basal conditions and in response to local 5-HT application (1 mM, air puff 10 s, 1 bar) (Fig 2a).…”

Section: Resultsmentioning

confidence: 99%

“…Overall, these results suggest a signi cant contribution of both astrocyte Ca 2+ signaling and astrocytic glutamatergic signaling for serotonergic synaptic actions. 5-HT2Rs family, including 5-HT2A, 5-HT2B and 5-HT2C, are highly expressed in different neuronal cell types, but also astrocytes 50 . Several evidences have related 5-HT2Rs with pathophysiology of MDD 76 , 5-HT2A and 5-HT2C in mPFC play a critical role in the regulation of mood disorders, and their antagonism has been related to antidepressant features 77 .…”

Section: Discussionmentioning

confidence: 99%

Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states

Perea

González-Arias

Esparza

et al. 2023

Preprint

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Astrocytes play crucial roles in brain homeostasis and are regulatory elements of neuronal and synaptic physiology. Astrocytic alterations have been found in Major Depressive Disorder (MDD) patients; however, the consequences of astrocyte Ca2+ signaling in MDD are poorly understood. Here, we found that corticosterone-treated mice (Cort-mice) showed altered astrocytic Ca2+ dynamics in mPFC both in resting conditions and during social interactions, in line with altered mice behavior. Additionally, Cort-mice displayed reduced serotonin (5-HT)-mediated Ca2+ signaling in mPFC astrocytes, and aberrant 5-HT-driven synaptic plasticity in layer 2/3 mPFC neurons. Downregulation of astrocyte Ca2+ signaling in naïve animals mimicked the synaptic deficits found in Cort-mice. Remarkably, boosting astrocyte Ca2+ signaling with Gq-DREADDS restored mood and cognitive deficits in Cort-mice to control levels. This study highlights the important role of astrocyte Ca2+ signaling for homeostatic control of brain circuits and behavior, but also reveals its potential therapeutic value for depressive-like states.

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“…Broad transcriptomic analysis of astroglial gene expression in mouse models of Huntington's disease and in human patients also demonstrates a general downregulation of important astroglial functional markers [7]. In major depressive disorder, a disease where substantial data from human post-mortem brain tissue illustrates involvement of astroglia in both disease onset and severity as well as in treatment-assisted recovery [158][159][160], astroglial atrophy has been observed without classic indications of reactivity [161,162]. Reductions in astroglial size and/or number have been noted in cortical and limbic regions in patients with mood disorders [163].…”

Section: Astrocyte Heterogeneity In Disease Statesmentioning

confidence: 98%

Astrocyte Heterogeneity in Regulation of Synaptic Activity

Kruyer

2022

Cells

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Our awareness of the number of synapse regulatory functions performed by astroglia is rapidly expanding, raising interesting questions regarding astrocyte heterogeneity and specialization across brain regions. Whether all astrocytes are poised to signal in a multitude of ways, or are instead tuned to surrounding synapses and how astroglial signaling is altered in psychiatric and cognitive disorders are fundamental questions for the field. In recent years, molecular and morphological characterization of astroglial types has broadened our ability to design studies to better analyze and manipulate specific functions of astroglia. Recent data emerging from these studies will be discussed in depth in this review. I also highlight remaining questions emerging from new techniques recently applied toward understanding the roles of astrocytes in synapse regulation in the adult brain.

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Astroglial Serotonin Receptors as the Central Target of Classic Antidepressants

Cited by 10 publications

References 258 publications

Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states

Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states

Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states

Astrocyte Heterogeneity in Regulation of Synaptic Activity

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