Astrocytes and extracellular matrix in extrasynaptic volume transmission

Abstract

Volume transmission is a form of intercellular communication that does not require synapses; it is based on the diffusion of neuroactive substances across the brain extracellular space (ECS) and their binding to extrasynaptic high-affinity receptors on neurons or glia. Extracellular diffusion is restricted by the limited volume of the ECS, which is described by the ECS volume fraction a, and the presence of diffusion barriers, reflected by tortuosity l, that are created, for example, by fine astrocytic processes or extracellular matrix (ECM) molecules. Organized astrocytic processes, ECM scaffolds or myelin sheets channel the extracellular diffusion so that it is facilitated in a certain direction, i.e. anisotropic. The diffusion properties of the ECS are profoundly influenced by various processes such as the swelling and morphological rebuilding of astrocytes during either transient or persisting physiological or pathological states, or the remodelling of the ECM in tumorous or epileptogenic tissue, during Alzheimer's disease, after enzymatic treatment or in transgenic animals. The changing diffusion properties of the ECM influence neuron -glia interaction, learning abilities, the extent of neuronal damage and even cell migration. From a clinical point of view, diffusion parameter changes occurring during pathological states could be important for diagnosis, drug delivery and treatment.

Matrix Metalloproteinase-9 Regulates Neuronal Circuit Development and Excitability

“…Indeed, angiogenesis requires remodeling of ECM (Heissig et al , 2003), and is delayed in postnatal MMP-9 −/− mice (Vu et al , 1998). Astrogliogenesis could be promoted by enhanced ECM stability MMP-9 −/− mice (Pan et al , 2014; Vargova & Sykova, 2014). However, no differences in blood vessel volume or astrocyte density were observed in adult MMP-9 −/− mice.…”

New Implications for the Melanocortin System in Alcohol Drinking Behavior in Adolescents: The Glial Dysfunction Hypothesis

“…At the other end, disturbances in extracellular levels of glutamate and other gliotransmitters have been associated to ethanol-mediated astroglial swelling. Indeed, acute treatment with ethanol triggers astrocyte swelling via Na + /K + /2Cl - cotransporter or the Na + /K + -ATPase, resulting in the release of glutamate, aspartate and taurine (Kimelberg et al, 1993; Allansson et al, 2001; Aschner et al, 2001a,b; Vargova and Sykova, 2014). Relevant to this point, extracellular levels of taurine are crucial for the ethanol-induced dopamine release in the Nac (Ericson et al, 2011).…”

Extracellular matrix in the CNS

“…Distinct ECM components ensheathe the axon initial segment (AIS), nodes of Ranvier, juxtaparanodes, and internodes and contribute functional compartmentalization of the axon. 48 The structure of the ECM, together with that of cell aggregates, myelin sheaths, and glial processes, creates preferential channels for the diffusion of molecules in a certain direction, such as along myelinated axons; this process is referred to as diffusion anisotropy. The brain-specific HA-linker protein 1 forms a complex with brevican and versican at the nodes of Ranvier; mice deficient in this linker protein have slow central axon conduction velocities.…”