Astrocyte Heterogeneity in Regulation of Synaptic Activity

Abstract

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.

Flow Cytometry Characterization and Analysis of Glial and Immune Cells from the Spinal Cord

“…Aging, injury, and disease trigger inflammatory responses in the CNS microenvironment that may result in neuronal loss and maladaptive plasticity, leading to dysfunction and irreversible conditions [9,53,54]. Pro-inflammatory cytokines released by astrocytes trigger transcriptional shifts, which may alter synaptic activity, resulting in behavioral and cognitive alterations [55][56][57].…”

“…In addition, they maintain the homeostasis of extracellular fluids, ions, and transmitters [4], provide glucose for neurons [5], modulate blood flow [6], contribute to synaptic plasticity [7], and thus, influence neuronal circuit function and animal behavior [8]. Several variants have been described, as well as subtypes found only in humans [9]. Different areas of the brain and spinal cord have specialized astrocytes that develop specific functions.…”

S100B Expression Plays a Crucial Role in Cytotoxicity, Reactive Oxygen Species Generation and Nitric Oxide Synthase Activation Induced by Amyloid β-Protein in an Astrocytoma Cell Line

“…This information unravels a crucial role of S100B in these phenomena, identifying a causative linkage between S100B expression and the occurrence of these phenomena participating in astrocyte reactivity. This may also be relevant in light of the heterogeneous cell population of astrocytes, which are known not to uniformly express the same molecular patterns [ 21 , 22 ].…”

“…However, the cell mechanisms participating in these complex phenomena lie out the goal of this brief communication and might be the object of future studies. Reasonably, the present results are subject to criticism of the data obtained on cell lines, and cannot be uncritically applied to all in vivo astrocyte populations, which are known to be heterogeneous and subject to environmental interferences [ 21 , 22 ]. In this regard, since the issue of classifying and defining astrocytes based on structure, biomarkers and function has always been a matter of debate, it cannot be ruled out that the present results cannot be referred “tout court” to all types of astrocytes.…”