Human astrocytes: structure and functions in the healthy brain

Abstract

Data collected on astrocytes’ physiology in the rodent have placed them as key regulators of synaptic, neuronal, network, and cognitive functions. While these findings proved highly valuable for our awareness and appreciation of non-neuronal cell significance in brain physiology, early structural and phylogenic investigations of human astrocytes hinted at potentially different astrocytic properties. This idea sparked interest to replicate rodent-based studies on human samples, which have revealed an analogous but enhanced involvement of astrocytes in neuronal function of the human brain. Such evidence pointed to a central role of human astrocytes in sustaining more complex information processing. Here, we review the current state of our knowledge of human astrocytes regarding their structure, gene profile, and functions, highlighting the differences with rodent astrocytes. This recent insight is essential for assessment of the relevance of findings using animal models and for comprehending the functional significance of species-specific properties of astrocytes. Moreover, since dysfunctional astrocytes have been described in many brain disorders, a more thorough understanding of human-specific astrocytic properties is crucial for better-adapted translational applications.

A cortical wiring space links cellular architecture, functional dynamics and hierarchies in humans

“…This approach revealed that divergent gradients of cell type-specific gene expression underpin intercardinal axes of the structural manifold, particularly of non-neuronal cell types. Increased glia-to-neuron ratios in transmodal compartments of the structural manifold may support higher order cognitive functions, given comparative evidence showing steep increases in this ratio from worms to rodents to humans [76][77][78][79] . Astrocytes, in particular, exhibit morphological variability that may lend a cellular scaffold to functional complexity and transmodal processing 76 .…”

“…Increased glia-to-neuron ratios in transmodal compartments of the structural manifold may support higher order cognitive functions, given comparative evidence showing steep increases in this ratio from worms to rodents to humans [76][77][78][79] . Astrocytes, in particular, exhibit morphological variability that may lend a cellular scaffold to functional complexity and transmodal processing 76 . For example, a uniquely human inter-laminar astrocyte was recently discovered with long fibre extensions, likely supporting long-range communication between distributed areas that may contribute to flexible, higher-order cognitive processing 80 .…”

Properties of human astrocytes and NG2 glia

“…However, the two studies cannot be directly compared because (a) different K + concentrations ([K + ]) were used in the pipette and bath solutions, which affects resting potentials and (b) the age of the patients analyzed varied greatly (4 months to 14 years vs. mean age of 34 years), which may explain the higher R i of cells in the former study ( R i = 288 MΩ vs. 140 MΩ) (for developmental changes in R i , see Kressin, Kuprijanova, Jabs, Seifert, & Steinhäuser, ). Referring to these two studies, it has been speculated that an apparently higher R i in human versus rodent astrocytes represents an evolutionary adaptation to the larger size of astrocytes, as it results in an increased length constant (Oberheim Bush & Nedergaard, ; Vasile et al, ). However, the whole cell current patterns shown in the papers by Bordey and Sontheimer () and Hinterkeuser et al () indicate that the authors had analyzed NG2 glial cells and not astrocytes.…”

“…Morphological studies revealed that astrocytes in the human cortex are larger, more complex and more diverse than those in rodents (Oberheim et al, 2009;Oberheim, Wang, Goldman, & Nedergaard, 2006;Vasile, Dossi, & Rouach, 2017). In addition to fibrous astrocytes in white matter and protoplasmic astrocytes in grey matter, two morphologically distinct subtypes of GFAP-positive cells, interlaminar and varicose projection astrocytes, are exclusively found in the cortex of higher primates (Colombo & Reisin, 2004;Colombo, Yáñez, Puissant, & Lipina, 1995;Oberheim et al, 2009;Sosunov et al, 2014).…”

Metabolome-Wide Mendelian Randomization Analysis of Emotional and Behavioral Responses to Traumatic Stress

“…Increased GP plasma levels have been associated with immunomodulating effects, drug-transporting proteins (e.g., histamine, serotonin), regulation of metabolism, and neuroinflammation (56,57). AGP expression in astrocytes also appears to mediate astrocyte-microglia interactions during neuroinflammation (58,59). In addition, GPs have been investigated as potential biomarkers for depression due to their ability to bind major classes of antidepressant drugs, such as tricyclic antidepressants and selective serotonin reuptake inhibitors (60).…”