Astrocytic modulation of neuronal signalling

Abstract

Neuronal signalling is a key element in neuronal communication and is essential for the proper functioning of the CNS. Astrocytes, the most prominent glia in the brain play a key role in modulating neuronal signalling at the molecular, synaptic, cellular, and network levels. Over the past few decades, our knowledge about astrocytes and their functioning has evolved from considering them as merely a brain glue that provides structural support to neurons, to key communication elements. Astrocytes can regulate the activity of neurons by controlling the concentrations of ions and neurotransmitters in the extracellular milieu, as well as releasing chemicals and gliotransmitters that modulate neuronal activity. The aim of this review is to summarise the main processes through which astrocytes are modulating brain function. We will systematically distinguish between direct and indirect pathways in which astrocytes affect neuronal signalling at all levels. Lastly, we will summarize pathological conditions that arise once these signalling pathways are impaired focusing on neurodegeneration.

A systematic review of the neuropathology and memory decline induced by monosodium glutamate in the Alzheimer’s disease-like animal model

“…In healthy brains, glutamate is continuously recycled between neurons and astrocytes in a continuous process called the glutamate–glutamine cycle, also referred to as the glutamate–GABA–glutamine cycle. This process ensures that glutamate concentrations rise briefly, up to 1 mM, for only half a second and then drop back to nanomolar levels ( Andersen and Schousboe, 2023 ; Dienel et al, 2023 ; Purushotham and Buskila, 2023 ). If high glutamate concentrations in the synaptic cleft persisted, the glutamatergic receptors on different parts of the cell, such as the dendritic spines and dendrites itself, would be tonic-activated ( Nimgampalle et al, 2023 ; Orlando et al, 2023 ; Piniella and Zafra, 2023 ).…”

Proteomic profiling of the brain from the <i>wobbler</i> mouse model of amyotrophic lateral sclerosis reveals elevated levels of the astrogliosis marker glial fibrillary acidic protein

“…43 Astrocytes represent a crucial cell type in the central nervous system that are involved in the maintenance of neuronal metabolism, synaptic function and the blood-brain barrier. 44 Pathological disturbances cause astrocyte activation, differentiation and morphological remodeling. Glial cell dysfunction, mainly involving microglia and astrocytes, was clearly established to occur in the nervous system of patients afflicted with amyotrophic lateral sclerosis.…”

Executive Summary of 2023 International Conference of the Korean Dementia Association (IC-KDA 2023): A Report From the Academic Committee of the Korean Dementia Association

“…Additionally, the research indicated that neuronal activity induces astrocytic volume expansion, leading to a secondary increase in calcium influx, potentially offering a protective effect on brain pathology. 20 21 These findings suggest that the benefits of gamma entrainment may originate from cascading secondary responses initiated by astrocytic changes. Overall, the research implicates the potential of 40 Hz acoustic neuromodulation in inducing glial alterations, providing a promising therapeutic pathway to ameliorate AD pathology.…”