β-Adrenergic Signaling Promotes Morphological Maturation of Astrocytes in Female Mice

Copyright © 2023 the authors..

Astrocytes play essential roles in the developing nervous system, including supporting synapse function. These astrocyte support functions emerge coincident with brain maturation and may be tailored in a region-specific manner. For example, gray matter astrocytes have elaborate synapse-associated processes and are morphologically and molecularly distinct from white matter astrocytes. This raises the question of whether there are unique environmental cues that promote gray matter astrocyte identity and synaptogenic function. We previously identified adrenergic receptors as preferentially enriched in developing gray versus white matter astrocytes, suggesting that noradrenergic signaling could be a cue that promotes the functional maturation of gray matter astrocytes. We first characterized noradrenergic projections during postnatal brain development in mouse and human, finding that process density was higher in the gray matter and increased concurrently with astrocyte maturation. RNA sequencing revealed that astrocytes in both species expressed α- and β-adrenergic receptors. We found that stimulation of β-adrenergic receptors increased primary branching of rodent astrocytes in vitro Conversely, astrocyte-conditional knockout of the β1-adrenergic receptor reduced the size of gray matter astrocytes and led to dysregulated sensorimotor integration in female mice. These studies suggest that adrenergic signaling to developing astrocytes impacts their morphology and has implications for adult behavior, particularly in female animals. More broadly, they demonstrate a mechanism through which environmental cues impact astrocyte development. Given the key roles of norepinephrine in brain states, such as arousal, stress, and learning, these findings could prompt further inquiry into how developmental stressors impact astrocyte development and adult brain function.SIGNIFICANCE STATEMENT This study demonstrates a role for noradrenergic signaling in the development of gray matter astrocytes. We provide new evidence that the β1-adrenergic receptor is robustly expressed by both mouse and human astrocytes, and that conditional KO of the β1-adrenergic receptor from female mouse astrocytes impairs gray matter astrocyte maturation. Moreover, female conditional KO mice exhibit behavioral deficits in two paradigms that test sensorimotor function. Given the emerging interest in moving beyond RNA sequencing to probe specific pathways that underlie astrocyte heterogeneity, this study provides a foundation for future investigation into the effect of noradrenergic signaling on astrocyte functions in conditions where noradrenergic signaling is altered, such as stress, arousal, and learning.

Medienart:	E-Artikel

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	Zur Gesamtaufnahme - volume:43
Enthalten in:	The Journal of neuroscience : the official journal of the Society for Neuroscience - 43(2023), 50 vom: 13. Dez., Seite 8621-8636

Sprache:	Englisch

Beteiligte Personen:	Rosenberg, Marci F [VerfasserIn] Godoy, Marlesa I [VerfasserIn] Wade, Sarah D [VerfasserIn] Paredes, Mercedes F [VerfasserIn] Zhang, Ye [VerfasserIn] Molofsky, Anna V [VerfasserIn]

Links:	Volltext

Themen:	β-adrenergic receptor Adrenergic Agents Astrocyte Brain development Journal Article Norepinephrine Receptors, Adrenergic Receptors, Adrenergic, beta Research Support, N.I.H., Extramural X4W3ENH1CV

Anmerkungen:	Date Completed 16.12.2023 Date Revised 19.01.2024 published: Electronic Citation Status MEDLINE

doi:	10.1523/JNEUROSCI.0357-23.2023

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	NLM363377956