Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments.

Petrelli, Francesco; Dallérac, Glenn; Pucci, Luca; Calì, Corrado; Zehnder, Tamara; Sultan, Sébastien; Lecca, Salvatore; Chicca, Andrea; Ivanov, Andrei; Asensio, Cédric S; Gundersen, Vidar; Toni, Nicolas; Knott, Graham William; Magara, Fulvio; Gertsch, Jürg; Kirchhoff, Frank; Déglon, Nicole; Giros, Bruno; Edwards, Robert H; Mothet, Jean-Pierre; ... (2018). Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments. (In Press). Molecular psychiatry Nature Publishing Group 10.1038/s41380-018-0226-y

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Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities and cognitive deficits commonly observed in psychiatric disorders. Here, we report the identification of a subset of cortical astrocytes that are competent for regulating dopamine (DA) homeostasis during postnatal development of the prefrontal cortex (PFC), allowing for optimal DA-mediated maturation of excitatory circuits. Such control of DA homeostasis occurs through the coordinated activity of astroglial vesicular monoamine transporter 2 (VMAT2) together with organic cation transporter 3 and monoamine oxidase type B, two key proteins for DA uptake and metabolism. Conditional deletion of VMAT2 in astrocytes postnatally produces loss of PFC DA homeostasis, leading to defective synaptic transmission and plasticity as well as impaired executive functions. Our findings show a novel role for PFC astrocytes in the DA modulation of cognitive performances with relevance to psychiatric disorders.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Chicca, Andrea and Gertsch, Jürg

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1359-4184

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

06 Mar 2019 15:52

Last Modified:

23 Oct 2019 14:05

Publisher DOI:

10.1038/s41380-018-0226-y

PubMed ID:

30127471

BORIS DOI:

10.7892/boris.125028

URI:

https://boris.unibe.ch/id/eprint/125028

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